Was zum Durchforsten !
Gruss Ludwig
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From: Stephen B. Strum MD, FACP
Medical Oncologist Specializing in Prostate Cancer
To:
Worktime for Response: 2 PM to 3:10 PM
Sent: Wednesday, November 22, 2006 3:22 AM
Subject: [P2P] HR- PSA 20 ...Treatments?
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Material posted here is intended for educational purposes only, and
must not be considered a substitute for informed medical advice from
your own physician.
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Dear Doctors:
Below is my husbands PC Digest...it is quite lengthy...sorry...I hope it is
in the format that you request...did my best.
My questions are at the end..
He is hormone refractory and has a PSA of 20..and probably ? higher since
last test. Thank you so very much for being here for all of us.
Eleanor Walmsley
Jim PC DIGEST 1993 - 2006
Michigan
Initial dx: 2-22-93 210 PSA Age 57
Back in the 80's, given the number of men I was
personally seeing with advanced PC being diagnosed in their 50's, I
advocated that men should begin to develop their "PSA PROFILE" by testing
STARTING at the age of 40. If there was a family history of either PC or BC
(breast cancer), I advocated starting testing at age 35. It is almost 20
years since the PSA has been commercially available. I have seen all kinds
of nonsense on "PSA having no value", PSA no longer useful", etc. Clearly,
every one of the treatments we do for men with PC is judged as successful or
as a failure based on the PSA profile. By "profile" I mean PSA slope,
velocity, doubling time, absolute value, Free PSA percentage--any or all of
these to profile the patient's status.
It does not take a rocket scientist to know if a tumor marker has value or
not in the diagnosis, prognosis and response to treatment of a particular
disease. For PC, the most common malignancy in man, PSA IS THE MOST
IMPORTANT BIOMARKER SO FAR DISCOVERED. What is painful to me is to continue
to see men diagnosed with advanced PC. THIS SHOULD NOT HAPPEN NOW--IT SHOULD
NOT HAVE HAPPENED 10 YEARS AGO OR MORE--AND IT SHOULD NOT HAPPEN IN THE
FUTURE. What is involved here is the most basic of common sense. If you see
smoke--evaluate it's nature--continue to observe to determine if you have a
fire of importance. A kid in 4th grade could figure this out. Folks, get the
word out for men to start testing their PSA as noted above, keep a
record--ideally a graph--to ensure that the slope of the PSA is close to
being flat. You can also determine the PSADT & velocity by a simple software
tool available via download at www.pcri.org in the resources, software
section. This is free; it is called PC TOOLS II.
Stage D 1 (T3, N2, MO)
Grade III
Gleason 9
DRE: Diffuse bilateral involvement probable right base and
apical extension.
TRUS: Gland volume 76 cc :
This is high risk PC per the categorization of
D'Amico et al.
High risk PC: any of these findings at diagnosis
Gleason score 8 or higher
PSA > 20
CS T2c or higher
Intermediate Risk PC: any of these findings at diagnosis
PSA >10 < = 20
GS 7 & not higher
CS T2b & not higher
Low Risk PC: any of these findings at diagnosis
PSA 10.0 or less
CS T2a or less
GS 6 or less
Original Pathology report: ...
Bladder base, biopsy: Prostatic adenocarcinoma, gleason combined scory 9
(4+5) involving dense fibromuscular tissue. Seminal vesicle ampulla,
biopsy: Seminal vesicle and fibroadipose connective tissue, no tumor
present.
Prostate, right, biopsy: Fibromuscular tissue extensively infiltrated by
high-grade prostatic adenocarcinoma. A few residual atrophic prostatic
glands are seen.
2-25-93 PSA 304 Treatment: Lupron & Flutamide for 4 months.
5-19-93 PSA 2.2
7-15-93 Started Radiation. Neutron/photon protocol. Stayed on hormones.
Here's where I think the above approach is missing:
(1) There is high volume PC based on absolute PSA and Gleason score. A
calculated tumor volume is over 200cc of PC. This is metastatic PC to either
bone &/or nodes or both--no matter what our staging studies show us.
(2) The optimal time to use RT is when the tumor burden is markedly reduced.
Moreover, in a clinical setting such as this, there is NO need to rush to a
local therapy. Starting RT after 4-5 mos of ADT is not my idea of triaging
the patient regarding his greatest needs.
(3) The nadir of the PSA on ADT is of therapeutic value in determining the
probability of Androgen Independent PC (AIPC), which in turn is an indicator
of an earlier need for chemotherapy or immunotherapy or both.
(4) The use of ADT always mandates the need to protect the patient from AD
(androgen deprivation) induced bone loss & release of bone-derived growth
factors.
(5) The evaluation of the patient for metastatic disease should also include
bone resorption markers like Deoxypyridinoline (DPD) & aminoterminal
procollagen propeptides of type 1 collagen (PINP).
For Dpd:
Quidel Corporation 2981 Copper Road Santa Clara, CA 95051 USA 8 a.m. to 5
p.m. PST Within the USA 800-524-6318 Outside the USA 408-616-4301 Fax
408-616-4310 U.S. Sales: brudy@quidel.comPurchasing Questions:
custsvc.qus@quidel.comTechnical Support: techsprt.qus@quidel.com
For PINP:
6. Focus on RT or Surgery in a setting like this takes away from the proper
emphasis on what is most threatening to the patient--systemic PC.
9-15-93 PSA: 0.25
2-15-94 PSA: 0.08
12-7-94 PSA 0.05
5-17-95 PSA 0.05
10-5-95 PSA 0.02
James did achieve an UD-PSA (undetectable PSA) on
ADT2 (2-drug ADT) but it took him 2 yrs 8 mos to do so. This suggests a
problem with mutated clones of PC that would warrant more aggressive
therapy. Also, I see no mention of testosterone levels while on ADT, nor
mention of bone integrity issues. No other markers are being checked for
expression by the PC population--this should have been done at baseline with
PAP, CEA, CGA & NSE checked. No focus on prolactin was given and this too
should have been checked.
Rana A, Habib FK, Halliday P, et al: A case for synchronous reduction of
testicular androgen, adrenal androgen and prolactin for the treatment of
advanced carcinoma of the prostate. Eur J Cancer 31A:871-5, 1995.
University Department of Surgery/Urology, Western General Hospital,
Edinburgh, U.K
The present study was undertaken mainly to investigate whether prolactin
manipulation combined with maximal androgen blockage improves the
effectiveness of treatment in advanced prostatic cancer. The efficacy of
oral hydrocortisone as an alternative to commercial anti-androgens in
reducing the adrenal androgens, and of bromocriptine in reducing the
prolactin level were also examined. A consecutive series of 30 patients with
untreated and advanced prostatic cancer were entered into a three-arm
prospective randomised trial. 10 patients received subcapsular orchiectomy
alone (arm 1), another 10 had subcapsular orchiectomy plus flutamide (arm
2), and the remaining 10 had subcapsular orchiectomy plus oral
hydrocortisone and bromocriptine (arm 3). Clinical and biochemical
parameters, including trans-rectal ultrasound-determined prostatic volumes,
hormonal profiles and radionuclide bone scan were evaluated at regular
intervals. At 12 months, serum testosterone was reduced by more than 90% in
all arms, however, maximum suppression of androstenedione, prolactin, and
reduction of prostatic volumes were only observed in arm 3; this was
reflected by the significant improvement in clinical response in arm 3
compared with other arms. This study suggests that a combined maximal
suppression of androgens and prolactin offers a significant improvement in
response over conventional treatments without prolactin suppression in the
treatment of advanced prostatic cancer. Importantly, a better clinical
outcome in arm 3 was still apparent at the end of 36 months.
Other issues relating to proper nutrition, checking on oxidized LDL levels,
Vit D-3 levels, essential fatty acid levels of omega-3 & omega-6 fatty
acids, etc are important aspects to the fine tuning of PC. Please obtain a
copy of "A Primer on Prostate Cancer, The Empowered Patient's Guide" by
Strum & Pogliano to read about this and much more; this book was written for
you--the PC patient & family. The Primer is available via a number of
sources:
Amazon at www.amazon.com
LEF (Life Extension Foundation) at www.lefprostate.org or 1-866-820-7457
Us Too at http://www.ustoo.com/ or (317-558-4858 or 800-808-7866), or
PCRI (Prostate Cancer Research Institute) at www.pcri.org or 310-743-2110.
3-15-96 PSA 4.62
5-22-96 PSA 8
The rapid doubling time is indicative of systemic PC.
6-7-96 He had a CT abdomen/pelvis, ="No definite enlarged retroperitoneal
or inguinal lymph nodes.
There is a 1 cm round structure posterior to the right iliac vessels which
could represent a lymph node and should be followed.
6-7-96 Bone Scan: increased activity within the anterior aspect of the
right third rib. This may simply represent a healing rib fracture, although
other etiologies including a metastatic bone lesion could not be excluded.
A small focal zone of increased activity within the upper thoracic spine at
the level of T2-3 may simply represent focally activity degenerative
change, although other etiologies including a metastatic bone lesion could
not be excluded.A comparison x-ray of the right sided ribs and upper
thoracic spine would be helpful.
6-18-96 Research Study report ... Prostate monoclonal antibody report.
Patient injected with 5.36 mCi of Indium-111 Capromab Pendetide and
imaged.. Impression: research study procedure raising concern for recurrent
tumor just inferior to the bifurcation of the right common
iliac vessels and just superior to the prostate bed on the right.
7-2-96 X-ray Right ribs: Multiple views demonstrate no fracture. No
Pneumothorx. No extrapleural soft tissue thickening.
7-2-96 X-ray Thoracic Spine: 2 views demonstrate extensive osteophyte
formation. No evidence of compression fractures or subluxation.
8-15-96 Switched from Lupron to Zoladex and discontinued the Flutamide.
9-15-96 PSA 2.58
6-15-97 PSA 3.00
9-15-97 PSA 3.49
Saw a urologist in Arizona
Your husband's care should ideally be under the guidance of a medical
oncologist specializing in PC.
10-15-97 PSA 1.9
1-15-98 PSA 3.2
4-15-98 PSA 2.5
Ret. to Michigan
5-20-98 PSA 4.3
10-15-98 PSA 1.9
The reason for the fluctuation in PSA from the dates of summer months to
Fall months is the difference in the labs from Michigan to Arizona. For
some reason they are much lower in AZ.
There is no reason not to use one laboratory such as
Quest or LabCorp. These are NATIONAL labs and the testing methodology is the
same whether the blood is drawn in a LabCorp or Quest facility in Osgosh or
in Ashland, Oregon.
Arizona
1-15-99 PSA 3.2
4-15-99 PSA 8.0
Michigan
6-15-99 PSA 14.4
Treatment = added Casodex and restarted Lupron
due to the 3 month regimen)
9-15-99 PSA 5.5
Arizona
10-15-99 PSA 3.3
1-15-00 PSA 2.8
Michigan
5-15-00 PSA 3.6
8-8-00 PSA 8.5
Added Proscar
10-2-00 PSA: 10.6
Discontinued Proscar/Casodex started lo-dose DES
1MG daily.
10-4-00 Bone Scan and Ct scans: The bone scans have shown an uptake in the
T -2-3 levels but they have always been described as osteophytes. In 2000
the report stated "most likely related to benign disease."
I like the use of DES but I routinely use 1mg tid with Coumadin or Lovenox
onboard. I also take measures to prevent gynecomastia.
Radiographic correlation may be useful, as neoplasm is not entirely
excluded." CT of Abdomen and Pelvis were always negative.
Arizona
11-15-00 PSA 4.2
2-6-01 PSA 4.3
5-2-01 PSA 4.2
Michigan
5-23-01 PSA 6.1
8-1-01 PSA 6.4
No change in treatment
Arizona
11-8-01 PSA 5.62
2-11-02 PSA 9.52
3-14-02 PSA 6.8
3-28-02 PSA 10.6
I think you have to be grateful for the good years with little significant
change in PSA. However, the studies above indicate that those times are
disappearing. Given the high Gleason score, the PSA also can UNDERstate the
situation regarding tumor volume.
Michigan
5-16-02 PSA 14.1
7-24-02 Had bone scan and MRI of thoracic spine. Result "destructive
lesions involving T3-4 vertebrae. There is a Hx of prostate cancer nd
findings are those of metatastic disease until proven otherwise."
8-12-02 PSA: 19.8
8-16-02 Treatment.. .. Radiation to the spine prescription dose
3500/fraction 250- 14 days.
8-30-02 PSA: 11.3
9-9-02 PSA: 7.9
Arizona
10-31-02 PSA: 2.05
1-20-03 PSA 1.0
4-24-03 PSA 3.4
Michigan
5-16-03 PSA 7.6
Had a bone scan --still describing large osteophyte, but does say
"bone metastasis or uptake of radiopharmaceutical within a tumor is an
additional consideration when given the patients history." CT of
Abdomen/pelvis=No definite findings suggesting metastatic disease.
8-1-03 PSA 18.4
8-22-03 PSA 19.2
Went off DES and started Hi dose Casodex 150 per day. Still on Lupron.
10-1-03 PSA 22.3
Arizona
10-23-03 PSA 13.30
10-30-03 PSA 12.2
11-06-03 MRI Thoracic Spine= metastasis of T3: tumor expands and extends
into the left transverse process. Discussed Zometa injections.
11-18-03 Bone Mineral Density mild irregularity in area of the T3 pedicle.
Rest is negative. Lumbar spine has severe spondylosis of the lower lumbar
spine with some minimal wedging of L 1.
11-21-03 Decision was made for surgery to remove as much of the tumor as
possible after CT and MRI indicated a large tumor almost surrounding the
spinal cord.
The reasoning was to alleviate the possibilty of paralysis, should the
tumor grow. A titanium cage was put in to replace the vertrebrae and
titanium rods and screws to support.
11-24-03 PSA 0.4
They took as much as they could of the tumor and now are prepping for more
radiation to the area, to see if they can keep the cells left from growing.
12-31-03 NM Whole Body Bone scan (Spine Mets) Plain films show no
radiographic abnormality. Show moderate nonspecific tracer accumulation at
T3 which corresponds to the site of prior surgery. There is a curvilinear
area of moderate tracer accumulation extending from the superior left aspect
of this vertebra. Here uptake here is nonspecific and may simply reflect
reactive bone in and area of prior surgery. However, the possibility of
residual neoplasm cannot be entirely excluded. The surrounding upper and
midthoracic vertebra show generally decreased tracer accumulation consistent
with prior radiation therapy.
There are no other sites of abnormal tracer accumulation to suggest
additional osseous metastasis. Degenerative-type uptake is seen in the AC
joints, both knees, left greater than right, and both feet. Renal and
bladder activity within physiologic limits.
1-07-04 Protascint scan MCS
#1 No abnormal uptake around the T3 level to match the findings on recent
bone scintigraphy. Prosthetic devices around the T3 level may limit
evaluation of subtle residual metastasis.
#2 Abnormal ProstaScint uptake within the prostatic fossa from prostatic
carcinoma. Advise correlation with most recent CT exam of the abdomen and
pelvis.
1-10-04 Received injection of Zometa. had bad reaction ... likens it to the
worst case of aching flu ever. Does not want to repeat.
This is called APR or acute phase response and CAN BE AVOIDED by using an
attenuated first dose of Zometa or Aredia.
Adami S, Bhalla AK, Dorizzi R, et al: The acute-phase response after
bisphosphonate administration. Calcif Tissue Int 41:326-331, 1987.
In patients who have never previously received bisphosphonate therapy, the
intravenous administration of 4-amino-1-hydroxybuthilidene
1,1-bisphosphonate (AHButBP)(Alendronate), 3-amino-1-hy-droxypropylidene- 1,
1-bisphosphonate (AHPrBP)(Aredia), or
6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) induced an
acute-phase response (APR) -irrespective of the underlying disease,
manifested by a fall in circulating lymphocyte number and serum zinc
concentration and in a rise in C-reactive protein (CRP); a febrile reaction
occurred in 30% of the patients. The APR was maximally expressed within
28-36 hours of i.v. administration of the bisphosphonates. And disappeared
2-3 days later despite continuous treatment. These effects were dose
dependent and the lowest doses necessary for an APR were lO mg of AHButBP
and AHPrBP, and 75 mg of AHHexBP. Doses up to 1,000 mg/day i.v. of
dichlormethanebisphosphonate Cl2MBP were devoid of these side effects. In
patients treated with either a single i.v. dose of amino-bisphosphonates
which resulted in an APR or with a suboptimal dose, a subsequent challenge
12-160 days later of the high dose failed to cause a rise in CRP or a fall
in the lymphocyte count. The desensitization to AHButBP or AHPrBP was also
seen following pretreatment with CI2MBP. These findings suggest that
bisphosphonates interact with macrophage-like cells resident in the skeleton
and stimulate interleukin-1 release which is responsible for the appearance
of the APR. At the same time, however, the bisphosphonates render these
cells insensitive to further stimulation for several months. This latter
observation might be relevant to the long-lasting suppression of bone
resorption observed after bisphosphonate therapy.
Since the APR is mediated by release of IL-1, agents that lower IL-1 can
also be used to prevent an APR.
INFO ON dR(down-regulation) of IL-1 beta: (THIS IS A BIG SECTION)
Agents that dR IL-1(senior author):
Curcumin: Jobin
Lipitor: Ascer
Glucosamine: Largo
PTX: Neuner
Indocin: Dash
NDGA: Dash
Nobiletin: Ishiwa
Silymarin: Zhao
TKIs:
Curcumin:
Jobin C, Bradham CA, Russo MP, et al: Curcumin blocks cytokine-mediated
NF-kappa B activation and proinflammatory gene expression by inhibiting
inhibitory factor I-kappa B kinase activity. J Immunol 163:3474-83, 1999.
Department of Medicine, Center for Gastrointestinal Biology and Disease,
University of North Carolina, Chapel Hill 27599, USA. job@med.unc.edu.
NF-kappa B plays a critical role in the transcriptional regulation of
proinflammatory gene expression in various cells. Cytokine-mediated
activation of NF-kappa B requires activation of various kinases, which
ultimately leads to the phosphorylation and degradation of I kappa B, the
NF-kappa B cytoplasmic inhibitor. The food derivative curcumin has been
shown to inhibit NF-kappa B activity in some cell types. In this report we
investigate the mechanism of action of curcumin on cytokine-induced
proinflammatory gene expression using intestinal epithelial cells (IEC).
Curcumin inhibited IL-1 beta-mediated ICAM-1 and IL-8 gene expression in
IEC-6, HT-29, and Caco-2 cells. Cytokine-induced NF-kappa B DNA binding
activity, RelA nuclear translocation, I kappa B alpha degradation, I kappa B
serine 32 phosphorylation, and I kappa B kinase (IKK) activity were blocked
by curcumin treatment. Wound-induced p38 phosphorylation was not inhibited
by curcumin treatment. In addition, mitogen-activated protein kinase/ERK
kinase kinase-1-induced IL-8 gene expression and 12-O-tetraphorbol
12-myristate 13-acetate-responsive element-driven luciferase expression were
inhibited by curcumin. However, I kappa B alpha degradation induced by
ectopically expressed NF-kappa B-inducing kinase or IKK was not inhibited by
curcumin treatment. Therefore, curcumin blocks a signal upstream of NF-kappa
B-inducing kinase and IKK. We conclude that curcumin potently inhibits
cytokine-mediated NF-kappa B activation by blocking a signal leading to IKK
activity.
Lipitor:
Ascer E, Bertolami MC, Venturinelli ML, et al: Atorvastatin reduces
proinflammatory markers in hypercholesterolemic patients. Atherosclerosis
177:6, 2004.
BACKGROUND: Reduction in cardiovascular events with statins has been in part
attributed to their anti-inflammatory properties. OBJECTIVE: Evaluate the
effects of atorvastatin on levels of inflammatory markers, such as tumor
necrosis factor-alpha (TNF), interleukins (IL-1 and IL-6), soluble
intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in
hypercholesterolemic patients (LDL-cholesterol >160 mg/dL). METHODS AND
RESULTS: Two lipid-lowering regimens were taken for 8 weeks. One set of
patients (n=45, 26 men, average 50 +/- 2 years of age) was subjected to
atorvastatin treatment (20-40 mg/day), plus diet recommendation. Another set
of patients (n=23, 12 men, average 53 +/- 3 years of age) went through diet
recommendation alone. Both groups were recommended to perform standard
physical activity. Plasma samples were collected after overnight fasting at
baseline and after 8 weeks for ELISA. The use of atorvastatin when compared
to diet alone, resulted in significant (P <0.0001) reductions for:
LDL-cholesterol (39.9% versus 4.4%), TNF (21.4% versus 2.9%), IL-6 (22.1%
versus 2.0%), IL-1 (16.4% versus 2.7%) and sICAM-1 (9.6% versus 0.1%),
respectively. The percentage of patients with CRP levels >3 mg/dL in the
atorvastatin group fell from 25.0 to 6.7% (P <0.0001) while in the diet
group the reduction was not significant. CONCLUSION: In hypercholesterolemic
patients, atorvastatin, compared to diet alone resulted in significant
reductions in levels of proinflammatory cytokines (TNF, IL-1 and IL-6) as
well as in sICAM-1 and CRP. Thus, statin-induced inhibition of inflammatory
markers may play an important role in the pharmacological and clinical
effects of statins seen in cardiovascular diseases.
Glucosamine:
Largo R, Alvarez-Soria MA, Diez-Ortego I, et al: Glucosamine inhibits
IL-1beta-induced NfkappaB activation in human osteoarthritic chondrocytes.
Osteoarthritis Cartilage 11:290-8, 2003.
OBJECTIVE: Glucosamine sulfate (GS) is a commonly used drug for the
treatment of osteoarthritis. The mechanism of the action of this drug does,
however, remain to be elucidated. In human osteoarthritic chondrocytes (HOC)
stimulated with a proinflammatory cytokine, we studied whether GS could
modify the NfkappaB activity and the expression of COX-2, a
NfkappaB-dependent gene. METHODS: Using HOC in culture stimulated with
interleukin-1 beta (IL-1beta), the effects of GS on NfkappaB activation,
nuclear translocation of NfkappaB/Rel family members, COX-1 and COX-2
expressions and syntheses and prostaglandin E2 (PGE2) concentration were
studied. RESULTS: GS significantly inhibited NfkappaB activity in a
dose-dependent manner, as well as the nuclear translocation of p50 and p65
proteins. Furthermore, GS-preincubated IL-1beta-stimulated HOC showed an
increase in IkappaBalpha in the cell cytoplasm in comparison with HOC
incubated with IL-1beta alone. GS also inhibited the gene expression and the
protein synthesis of COX-2 induced by IL-1beta, while no effect on COX-1
synthesis was seen. GS also inhibited the release of PGE2 to conditioned
media of HOC stimulated with IL-1beta. CONCLUSIONS: GS inhibits the
synthesis of proinflammatory mediators in HOC stimulated with IL-1beta
through a NfkappaB-dependent mechanism. Our study further supports the role
of GS as a symptom- and structure-modifying drug in the treatment of OA.
PTX:
Neuner P, Klosner G, Schauer E, et al: Pentoxifylline in vivo
down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis
factor-alpha by human peripheral blood mononuclear cells. Immunology
83:262-7, 1994.
Department of Special and Environmental Dermatology, University of Vienna,
Austria
ABSTRACT: Pentoxifylline (PTX) is a methylxanthine compound known to
inhibit the production of tumour necrosis factor-alpha (TNF-alpha), which is
an important inflammatory mediator. There is also recent evidence that PTX
may influence other inflammatory cytokines, such as interleukin-1 (IL-1) and
IL-6. Due to the therapeutic implications, the present study addressed the
in vivo effects of PTX on the release of TNF-alpha, IL-1 beta, IL-6 and IL-8
by human peripheral blood mononuclear cells (PBMC). When PBMC were obtained
from healthy volunteers ingesting 5 x 400 mg PTX orally for 2 days, the
ability of PBMC cultured for 24 hr to release TNF-alpha was significantly
reduced, while secretion of IL-1 beta, IL-6 and IL-8 was not affected.
However, when PBMC were obtained from the same individuals 5 days after PTX
had been stopped, the release of all four cytokines was significantly
suppressed. This effect appeared to be exerted at the transcriptional level,
since Northern blot analysis revealed reduced cytokine transcripts. In order
to gain more insight into the effect of PTX on cytokine release, PBMC were
obtained from normal volunteers, either stimulated with lipopolysaccharide
(LPS) or left unstimulated, and subsequently incubated in vitro with PTX for
48 hr. Under these conditions, only TNF-alpha was found to be reduced by
PTX, while IL-1 beta and IL-8 were not affected, IL-6 was even enhanced.
However, when PBMC were incubated with PTX for 24 hr, PTX removed thereafter
by medium change and cells further cultured, the production not only of
TNF-alpha but also of IL-1 beta, IL-6 and IL-8 was reduced, demonstrating
that PTX exerts diverse (inhibitory) effects on cytokine release by PBMC.
Indocin & NDGA:
Dash PK, Moore AN: Enhanced processing of APP induced by IL-1 beta can be
reduced by indomethacin and nordihydroguaiaretic acid. Biochem Biophys Res
Commun 208:542-8, 1995.
Abnormal processing of the amyloid precursor protein (APP) is thought to
contribute to the formation of amyloid plaques in Alzheimer's disease.
Several studies suggest that inflammation, and possibly the cytokines
released during the inflammatory process, may participate in the plaque
formation. We have utilized a cell culture system to examine the effects of
the cytokine interleukin-1 beta (IL-1 beta) on the processing of APP. We
present data to show that IL-1 beta increases the maturation of APP and
causes enhanced processing of the full length APP isoforms. In addition, as
reported previously in HUVEC cells, IL-1 beta increases the secretion of APP
in PC12 cells. Indomethacin and NDGA, reported inhibitors of the
cyclooxygenase and lipoxygenase pathways, respectively, block these effects,
suggesting the involvement of prostaglandins and leukotrienes in IL-1 beta
mediated APP processing.
Nobiletin:
Ishiwa J, Sato T, Mimaki Y, et al: A citrus flavonoid, nobiletin, suppresses
production and gene expression of matrix metalloproteinase 9/gelatinase B in
rabbit synovial fibroblasts. J Rheumatol 27:20-5, 2000.
OBJECTIVE: Flavonoids including nobiletin are known to exert many biological
actions in vitro. We investigated the chondroprotective effect of citrus
flavonoids, especially nobiletin, using cultured rabbit synovial fibroblasts
and articular chondrocytes. METHODS: We examined the effects of citrus
flavonoids on the production and gene expression of matrix
metalloproteinases (MMP) and prostaglandin E2 (PGE2)production in rabbit
synovial fibroblasts. RESULTS: Six flavonoids isolated from Citrus depressa
Rutaceae including tangeretin, 6-demethoxytangeretin, nobiletin,
5-demethylnobiletin, 6-demethoxynobiletin, and sinensetin suppressed the
interleukin 1 (IL-1) induced production of proMMP-9/progelatinase B in
rabbit synovial cells in a dose dependent manner (<64 microM); nobiletin
most effectively suppressed proMMP-9 production along with the decrease in
its mRNA. Nobiletin also reduced IL-1 induced production of PGE2 in the
synovial cells, but did not modify the synthesis of total protein. These
suppressive effects of nobiletin were also observed in rabbit articular
chondrocytes. Nobiletin inhibited proliferation of rabbit synovial
fibroblasts in the growth phase. CONCLUSION: These results suggest nobiletin
is a novel antiinflammatory candidate that has the potential to inhibit PGE2
production, matrix degradation of the articular cartilage, and pannus
formation in osteoarthritis and rheumatoid arthritis.
Silymarin:
Zhao J, Sharma Y, Agarwal R: Significant inhibition by the flavonoid
antioxidant silymarin against 12-O-tetradecanoylphorbol 13-acetate-caused
modulation of antioxidant and inflammatory enzymes, and cyclooxygenase 2 and
interleukin-1alpha expression in SENCAR mouse epidermis: implications in the
prevention of stage I tumor promotion. Mol Carcinog 26:321-33, 1999.
The flavonoid antioxidant silymarin is used clinically in Europe and Asia
for the treatment of liver diseases and is sold in the United States and
Europe as a dietary supplement. Recently we showed that silymarin possesses
exceptionally high cancer-preventive effects in different mouse skin
carcinogenesis models and affords strong anticancer effects in human skin,
cervical, prostate, and breast carcinoma cells. More recently, we showed
that the anti-tumor-promoting effect of silymarin is primarily targeted
against stage I tumor promotion in mouse skin (Cancer Res 1999;59:622-632).
Based on this recent study, in this report, further investigations were made
to identify and define the biochemical and molecular mechanisms of
silymarin's effect during stage I tumor promotion in mouse skin. A single
topical application of silymarin at 3-, 6-, and 9-mg doses onto SENCAR mouse
skin followed 30 min later with 12-O-tetradecanoylphorbol 13-acetate (TPA)
at a 3-microg dose resulted in a 76-95% inhibition (P < 0.001) of TPA-caused
skin edema. Similarly, these doses of silymarin also showed 39-90%, 29-85%,
and 15-67% protection (P < 0.05 or 0.001), against TPA-caused depletion of
epidermal superoxide dismutase, catalase, and glutathione peroxidase
activity, respectively. Pretreatment of mice with silymarin also produced
highly significant inhibition of TPA-caused induction of epidermal lipid
peroxidation (47-66% inhibition, P < 0.001) and myeloperoxidase activity
(56-100% inhibition, P < 0.001). In additional studies assessing the effect
of silymarin on arachidonic acid metabolism pathways involving lipoxygenase
and cyclooxygenase (COX), similar doses of silymarin showed highly
significant inhibition of TPA-caused induction of epidermal lipoxygenase
(49-77% inhibition, P < 0.001) and COX (35-64% inhibition, P < 0.01 or
0.001) activity. Western immunoblot analysis showed that the observed effect
of silymarin on COX activity was due to inhibition of TPA-inducible COX-2
with no change in constitutive COX-1 protein levels. In other studies,
silymarin also showed dose-dependent inhibition of TPA-caused induction of
epidermal interleukin 1alpha (IL-1alpha) protein (39-72% inhibition, P <
0.005 or 0.001) and mRNA expression. Taken together, the results from these
biochemical and molecular studies further substantiate our recent
observation of silymarin's anti-tumor-promoting effects primarily at stage I
tumor promotion. Furthermore, the observed inhibitory effects of silymarin
on COX-2 and IL-1alpha should be further explored to develop preventive
strategies against those cancers in which these molecular targets play one
of the causative roles, such as non-melanoma skin, colon, and breast cancers
in humans.
1-26-04 Complaining of pain in the area of the surgery (T3). Says it is
muscular feeling, near the shoulder blade along the site of surgery. It is
worse at night so is taking 2 vicodin at night. Had radiation to the area
200 rads to 2000 with IMRT for T2,N2,MO prostate cancer.
2-6-04 PSA 0.5
No treatment change. Still on Lupron and 50mg Casodex.
4-19-04 PSA 0.6
CT Pelvis W contrast: Prostate gland is atrophic likely related to previous
radiation therapy. Small left infuinal hernia containing a loop of sigmoid
colon. No evidence of obstruction, No evidence of metastases in the abdomen
and pelvis.
MICHIGAN
5-27-04 PSA 0.6 Testosterone 38 No treatment change.
8-26-04 PSA 1.2 Testosterone 21
No treatment change.
ARIZONA
12-06-04 PSA 2.91
12-14-04 Whole Body Bone Scan Impression:
1. Degree of uptake at T3 is less than prior exam.
2. Slightly inhomogeneous uptake in lower thoracic spine along the lateral
aspect.
Concern about the lower thoracic on the right side, whether it is
degenerative or osteoarthritic need confirmation on CT scheduled in Jan.
3.No definite new lesions are identified.
4.Increased uptake in the projection of the shoulders and acromioclavicular
joints bilaterally. Knees tarsal bones and ankles compatible with
degenerative and osteoarthritic changes.
Two subtle linear areas of increased uptake noted in the left inguinal
region probably on the basis of urinary contamination.
1-13-05 CT Abdomen & Pelvis
No change from the 4-19-04 CT.
Mild degenerative changes at the costovertebral margins of the T 1 0-12th
ribs. This likely accounts for the mildly increased uptake on the 12-14-04
bone scan. No evidence of metastases.
1-14-05 PSA 6.74
MR Thoracic spine/Lumbar spine/Cervical spine
Nothing to suggest recurrent tumor in the thoracic spine. Some
post-operative changes in the soft tissues dorsal to the thecal sac at
T2,3,4.and at the resection site of the left pedicle and lamina and
transverse process of T3. No central canal stenosis and no evidence of bone
lesions.
Lumbar-there is no evidence of skeletal metastasis in the visualized spine.
Cervical- residual scar from surgery , no evidence of metastasis. It is
impossible to exclude a small amount of recurrent or residual tumor within
the scar tissue of the operative bed, but there is no focal lesion. The
signal in the cord is normal.
2-1-05 BMA
Lumbar spineBl\1D: 1.081 g1cm2 Ll-2).
T -score = +0.3 (S.D.'s from peak bone mass).
Left femoral neck Bl\1D: 0.855 g1cm2.
T -score = -0.6 (S.D.'s from peak bone mass).
Left ultradistal radius Bl\1D: 0.463 g1cm2.
T-score= -1.4 (S.D.'s from peak bone mass).
When compared to 11-18-03 lumbar spine has =1.7% change.
Femoral neck has = +0.4% change.
Ultradistal radius has = -1.5% change.
None of which are statistically significant.
2-17-05 PSA 8.97 Stopped Casodex
3-9-05 PSA 10.98 Prescription for Zocor ..No change in treatment.discussed
Treatment options.
MICHIGAN
5-20-05 PSA 14.6
Dr.did not recommend chemo at this time, due to lack of demonstrative
metatastic disease.
The prostate area appears atrophic; where does the doc in Michigan think the
PSA is coming from?? This is metastatic disease. What is amazing is how long
Julian has gone without the use of chemotherapy. He should be treated with
chemotherapy. He can be tried on HDK first, if so desired.
7-11-05 Had pneumonia-- in hospital over night.
7-28-05 Saw Dr. (Heart) no changes in his meds..
8-16-05 X-ray of thorax for pneumonia
Results: Increased density in right upper lobe. Probably inflammatory.but
neoplasm cannot be excluded.
Thickening of the right paratracheal & paravertebral soft tissues,
upper aspect of the thorax.
9-6-05 PET SCAN. Family MD ordered for lungs.
Results:No suspicious hyper metabolite areas seen in right upper lobe to
suggest malignancy.
Increased uptake in upper thoracic spine most likely due to degenerative
Post surgical changes.
Increased FDG uptake in the large bowel(ascending colon, =inflammatory
changes. Should examine??
9-7-05 PSA 20.6
10-11-05 PSA 40.4 Dr. recommends Taxotere.
Finally.
ARIZONA
11-02-05 PSA 45.59 Treatment: DES 3mg with coumadin
11-18-05 PSA 33.25 at Mayo Family Clinic
1-3-06 PSA 13.47 still on DES
3-3-06 PSA 8.82 " """
I often recommend a combination of Taxotere PLUS DES with Coumadin on board.
Another combination is Taxotere + Pulse Calcitriol. Another is Taxotere +
Carboplatin =/- DES or Calcitriol.
MICHIGAN
5-4-06 PSA 12.4 Stayed on DES
7-10-06 PSA 17.6 " " "
ARIZONA
10-24-06 PSA 20.83 still on 3mg DES.
Sometimes stopping DES can result in a withdrawal response. Clearly, there
is a need to change therapy.
Saw Dr. and he recommended a clinical trial
The Use of Chemotherapy, Docetaxel (Taxotere),and Prednisone with or without
a Monoclonal Antibody, Bevacizumab, to Treat Men with Prostate Cancer Not
Responding to Hormone Treatments.
That is reasonable.
A CT will be done on Wed. this week..then we will see Dr. for results on
Fri. after Thanksgiving.
11-13-06 Jim in hospital with pneumonia.will probably postpone CT until he
is stronger.
11-21-06 Jim is home from hospital with oxygen as his oxygen level will
not stablize.
Questons:
Would you recommend this clinical trial???
Yes, but Jim has to be off the DES, & the pneumonia completely resolved with
good oxygenation. Of course, my opinion is of limited value without having
seen Jim in person.
Would you recommend ANY clinical trial?/
There is a Taxotere + Vit D trial but I think Jim is not eligible since
prior Taxotere. Check Google using word "Asentar".
Would you suggest other treatments ie...Keto lodose..calcitriol...casodex
150...potential vaccine (trial?)
HDK(high-dose ketoconazole) or Nizoral at standard dose is my choice. I am
not in favor of using the lower dose regimen in light of what I have
personally seen over 20 years using the standard HDK regimen. Read about
this in http://prostate-cancer.org/resource/pdf/Is4-3.pdf or obtain a copy
of the full paper from J of Urology:
Scholz M, Jennrich R, Strum S, et al: Long-term outcome for men with
androgen independent prostate cancer treated with ketoconazole and
hydrocortisone. J Urol 173:1947-52, 2005. PMID 15879788
PURPOSE: The combination of high dose ketoconazole and hydrocortisone (HDK)
is active against androgen independent prostate cancer (AIPC). Median
response times with HDK tend to be brief but a significant minority of AIPC
patients benefit with extended responses. Well characterized response and
survival information, especially in the cohort of patients who experience
these longer, more durable, responses has not been previously reported.
Characterization of this subgroup is of particular interest since men with
long-term responses derive the greatest benefit from HDK therapy. MATERIALS
AND METHODS: The medical records of 78 patients with AIPC treated with HDK
between March 1991 and February 1999 were retrospectively reviewed. Baseline
clinical and laboratory factors predictive of prolonged response and
survival were identified. RESULTS: The median baseline prostate specific
antigen (PSA) before the initiation of HDK was 25.1. The number of patients
with zero, 1 to 3, and more than 3 lesions on bone scan were 25, 35 and 18,
respectively. Median and mean time to PSA progression was 6.7 and 14.5
months. Median and mean survival time was 38.0 and 42.4 months,
respectively. Response time and survival were highly correlated (r = 0.799).
A total of 34 (44%) men had a greater than 75% decrease in PSA. The median
survival times in men with more vs less than a 75% decrease were 60 vs 24
months, respectively. In a Cox proportional hazard regression, prolonged
survival was predicted by percent PSA decrease, extent of disease on bone
scan and baseline PSA. CONCLUSIONS: Ketoconazole can induce prolonged
responses, occasionally lasting for years. Long responses are more likely to
occur in men initiating HDK earlier in the course of disease before the
cancer burden becomes excessive.
cytoxan/predisone other???
There are a number of regimens that involve other chemo agents. A
comprehensive list is shown below:
Taxotere + Carbo + Celebrex
Taxotere + Calcitriol 0.5mcg/kg
Taxotere + Gleevec
Taxotere + Clusterin ASO
Taxotere + Revamid (clinical trial via CTRC.com)
Taxotere + Gemzar (alternate is Taxol alternating weekly with Gemzar)
Taxotere + Capecitabine
Taxotere + Velcade + Gleevec
Cytoxan + 5-FU + DES + Coumadin (Servadio Regimen)
Cytoxan + DES + Coumadin
Leukine + Thalidomide (Leukine dose is 250mcg 4 times per week; Thalidomide
is 100mg/hs); Lovenox suggested to prevent thrombosis
Leukine + Accutane or ATRA
EE + Lanreotide ( ethinylestradiol (EE) is not supposed to cause
thrombosis; would use anti-coagulant)
DXM + Lanreotide Q 2wks vs Q wk (Koutsilieris Regimen)
HDK + HC
HDK + Triamcinolone
HDK + Adria
HDK + Adria + Velban + Emcyt + Coumadin
Mitoxantrone + Prednisone
2C4
Atrasentan vs Bosentran
Avastin + Taxotere or another chemo combination
Velban + Mitomycin C weekly (low dose for each drug)
Oral
Cytoxan
Xeloda
Etoposide
IV
Taxotere
Taxol
Carboplatin (paraplatin)
Cisplatin
Abraxane
Adriamycin (doxorubicin)
Novantrone (Mitoxantrone)
Navelbine
Velban
Mitomycin C
5-FU
Cytoxan
Vincristine
Gemzar (gemcitabine)
Etoposide (VP-16)
Taxol or Taxotere followed 24 hrs later by Carboplatin
Taxane followed by 5-FU
Adriamycin (24 hr infusion) followed by Zometa (one hour infusion)
Gemzar followed by 96hrs then Taxotere
Adriamycin followed by Taxol, then 48hrs washout, then Gemzar (24hr
infusion)
Adriamycin(4hr infusion) followed by Taxol (24hr infusion)
I have heard/read several comments about trying ALL other treatments before
going to chemo...
you thoughts?...
I think Jim has seen just about all major approaches with the exception of
HDK(high-dose ketoconazole) or Nizoral.
The Dr. we see here at Mayo clinic is in Hematology/oncology, but his field
is Interests:Lymphoma,Breast Cancer, Bone Marrow Transplantation,
Castleman's Disease, Myeloproliferative Disorders.
It seems none of them here are "PC" specialists..
That's why I entered this field many years ago--a huge need for this. You
may wish to get another opinion but first ask your local MD if he will work
with a medical oncologist specializing in PC from a distance. You could get
started on a program and then follow it up locally.
Names of medical oncologists with full practice offices:
Mark Scholz,& Richard Lam, MDs
Prostate Oncology Specialists
4676 Admiralty Way, Suite 101
Marina del Rey, CA 90292
T:310-827-7707
F:310-574-4002
Glenn Tisman MD Inc.
13025 Bailey Street
Whittier, CA 90601
T: 562-789-8822
F: 562-698-4582
E: gtisman@doctisman.com
Steven Tucker, M.D.
Director, Prostate & GU Oncology Program
The Angeles Clinic & Research Institute
11818 Wilshire Blvd., Suite 200
Los Angeles, CA 90025
T: 310.231.2121
F: 310.231.2172
E: stucker@theangelesclinic.org
W: www.theangelesclinic.org
M: 310-266-3380
(Tucker is now in Singapore)
Bob Leibowitz, M.D.
Compassionate Onc Medical Group
2080 Century Park E
Suite 1005
Los Angeles, CA 90067-2009
T: 310-229-3555
F: 310-229-3554
francine@compassionateoncology.org
Myers and I only do consultations; we do not have full service offices
regarding administration of chemotherapy.
Charles "Snuffy" Myers, MD
American Institute of Disease of the Prostate &
Foundation for Research and Education
P.O. Box 307
Free Union, VA 22940
960 Bent Oaks Drive (Office)
Earlyville, VA 22936
434-964-0212
Fax: 434-964-0216
snuffym@aol.com
Contact: Rose Myers.
rosemyers@earthlink.net
Stephen B. Strum, MD, FACP
538 Granite Street
Ashland, OR 97520
T: (O) 541-201-0219
Fax 541-482-1284
stephen@sbstrum.com
I have extremely strict conditions re: the patients who I accept. Given
this, and the complexity of Jim's case, and my current work load, I would
suggest one of the other docs listed above. I wish you well.
If the above has been helpful to you, consider a tax-deductible donation to
the PCRI (Prostate Cancer Research Institute). Note that I am no longer
affiliated with that organization but it is the best one to provide help to
the man with PC.
Stephen B. Strum MD, FACP
Medical Oncologist Specializing in Prostate Cancer
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#######################################
From: Stephen B. Strum MD, FACP
Medical Oncologist Specializing in Prostate Cancer
To:
Worktime for Response: 2 PM to 3:10 PM
Sent: Wednesday, November 22, 2006 3:22 AM
Subject: [P2P] HR- PSA 20 ...Treatments?
**********
Material posted here is intended for educational purposes only, and
must not be considered a substitute for informed medical advice from
your own physician.
**********
Dear Doctors:
Below is my husbands PC Digest...it is quite lengthy...sorry...I hope it is
in the format that you request...did my best.
My questions are at the end..
He is hormone refractory and has a PSA of 20..and probably ? higher since
last test. Thank you so very much for being here for all of us.
Eleanor Walmsley
Jim PC DIGEST 1993 - 2006
Michigan
Initial dx: 2-22-93 210 PSA Age 57
personally seeing with advanced PC being diagnosed in their 50's, I
advocated that men should begin to develop their "PSA PROFILE" by testing
STARTING at the age of 40. If there was a family history of either PC or BC
(breast cancer), I advocated starting testing at age 35. It is almost 20
years since the PSA has been commercially available. I have seen all kinds
of nonsense on "PSA having no value", PSA no longer useful", etc. Clearly,
every one of the treatments we do for men with PC is judged as successful or
as a failure based on the PSA profile. By "profile" I mean PSA slope,
velocity, doubling time, absolute value, Free PSA percentage--any or all of
these to profile the patient's status.
It does not take a rocket scientist to know if a tumor marker has value or
not in the diagnosis, prognosis and response to treatment of a particular
disease. For PC, the most common malignancy in man, PSA IS THE MOST
IMPORTANT BIOMARKER SO FAR DISCOVERED. What is painful to me is to continue
to see men diagnosed with advanced PC. THIS SHOULD NOT HAPPEN NOW--IT SHOULD
NOT HAVE HAPPENED 10 YEARS AGO OR MORE--AND IT SHOULD NOT HAPPEN IN THE
FUTURE. What is involved here is the most basic of common sense. If you see
smoke--evaluate it's nature--continue to observe to determine if you have a
fire of importance. A kid in 4th grade could figure this out. Folks, get the
word out for men to start testing their PSA as noted above, keep a
record--ideally a graph--to ensure that the slope of the PSA is close to
being flat. You can also determine the PSADT & velocity by a simple software
tool available via download at www.pcri.org in the resources, software
section. This is free; it is called PC TOOLS II.
Stage D 1 (T3, N2, MO)
Grade III
Gleason 9
DRE: Diffuse bilateral involvement probable right base and
apical extension.
TRUS: Gland volume 76 cc :
D'Amico et al.
High risk PC: any of these findings at diagnosis
Gleason score 8 or higher
PSA > 20
CS T2c or higher
Intermediate Risk PC: any of these findings at diagnosis
PSA >10 < = 20
GS 7 & not higher
CS T2b & not higher
Low Risk PC: any of these findings at diagnosis
PSA 10.0 or less
CS T2a or less
GS 6 or less
Original Pathology report: ...
Bladder base, biopsy: Prostatic adenocarcinoma, gleason combined scory 9
(4+5) involving dense fibromuscular tissue. Seminal vesicle ampulla,
biopsy: Seminal vesicle and fibroadipose connective tissue, no tumor
present.
Prostate, right, biopsy: Fibromuscular tissue extensively infiltrated by
high-grade prostatic adenocarcinoma. A few residual atrophic prostatic
glands are seen.
2-25-93 PSA 304 Treatment: Lupron & Flutamide for 4 months.
5-19-93 PSA 2.2
7-15-93 Started Radiation. Neutron/photon protocol. Stayed on hormones.
Here's where I think the above approach is missing:
(1) There is high volume PC based on absolute PSA and Gleason score. A
calculated tumor volume is over 200cc of PC. This is metastatic PC to either
bone &/or nodes or both--no matter what our staging studies show us.
(2) The optimal time to use RT is when the tumor burden is markedly reduced.
Moreover, in a clinical setting such as this, there is NO need to rush to a
local therapy. Starting RT after 4-5 mos of ADT is not my idea of triaging
the patient regarding his greatest needs.
(3) The nadir of the PSA on ADT is of therapeutic value in determining the
probability of Androgen Independent PC (AIPC), which in turn is an indicator
of an earlier need for chemotherapy or immunotherapy or both.
(4) The use of ADT always mandates the need to protect the patient from AD
(androgen deprivation) induced bone loss & release of bone-derived growth
factors.
(5) The evaluation of the patient for metastatic disease should also include
bone resorption markers like Deoxypyridinoline (DPD) & aminoterminal
procollagen propeptides of type 1 collagen (PINP).
For Dpd:
Quidel Corporation 2981 Copper Road Santa Clara, CA 95051 USA 8 a.m. to 5
p.m. PST Within the USA 800-524-6318 Outside the USA 408-616-4301 Fax
408-616-4310 U.S. Sales: brudy@quidel.comPurchasing Questions:
custsvc.qus@quidel.comTechnical Support: techsprt.qus@quidel.com
For PINP:
6. Focus on RT or Surgery in a setting like this takes away from the proper
emphasis on what is most threatening to the patient--systemic PC.
9-15-93 PSA: 0.25
2-15-94 PSA: 0.08
12-7-94 PSA 0.05
5-17-95 PSA 0.05
10-5-95 PSA 0.02
ADT2 (2-drug ADT) but it took him 2 yrs 8 mos to do so. This suggests a
problem with mutated clones of PC that would warrant more aggressive
therapy. Also, I see no mention of testosterone levels while on ADT, nor
mention of bone integrity issues. No other markers are being checked for
expression by the PC population--this should have been done at baseline with
PAP, CEA, CGA & NSE checked. No focus on prolactin was given and this too
should have been checked.
Rana A, Habib FK, Halliday P, et al: A case for synchronous reduction of
testicular androgen, adrenal androgen and prolactin for the treatment of
advanced carcinoma of the prostate. Eur J Cancer 31A:871-5, 1995.
University Department of Surgery/Urology, Western General Hospital,
Edinburgh, U.K
The present study was undertaken mainly to investigate whether prolactin
manipulation combined with maximal androgen blockage improves the
effectiveness of treatment in advanced prostatic cancer. The efficacy of
oral hydrocortisone as an alternative to commercial anti-androgens in
reducing the adrenal androgens, and of bromocriptine in reducing the
prolactin level were also examined. A consecutive series of 30 patients with
untreated and advanced prostatic cancer were entered into a three-arm
prospective randomised trial. 10 patients received subcapsular orchiectomy
alone (arm 1), another 10 had subcapsular orchiectomy plus flutamide (arm
2), and the remaining 10 had subcapsular orchiectomy plus oral
hydrocortisone and bromocriptine (arm 3). Clinical and biochemical
parameters, including trans-rectal ultrasound-determined prostatic volumes,
hormonal profiles and radionuclide bone scan were evaluated at regular
intervals. At 12 months, serum testosterone was reduced by more than 90% in
all arms, however, maximum suppression of androstenedione, prolactin, and
reduction of prostatic volumes were only observed in arm 3; this was
reflected by the significant improvement in clinical response in arm 3
compared with other arms. This study suggests that a combined maximal
suppression of androgens and prolactin offers a significant improvement in
response over conventional treatments without prolactin suppression in the
treatment of advanced prostatic cancer. Importantly, a better clinical
outcome in arm 3 was still apparent at the end of 36 months.
Other issues relating to proper nutrition, checking on oxidized LDL levels,
Vit D-3 levels, essential fatty acid levels of omega-3 & omega-6 fatty
acids, etc are important aspects to the fine tuning of PC. Please obtain a
copy of "A Primer on Prostate Cancer, The Empowered Patient's Guide" by
Strum & Pogliano to read about this and much more; this book was written for
you--the PC patient & family. The Primer is available via a number of
sources:
Amazon at www.amazon.com
LEF (Life Extension Foundation) at www.lefprostate.org or 1-866-820-7457
Us Too at http://www.ustoo.com/ or (317-558-4858 or 800-808-7866), or
PCRI (Prostate Cancer Research Institute) at www.pcri.org or 310-743-2110.
3-15-96 PSA 4.62
5-22-96 PSA 8
The rapid doubling time is indicative of systemic PC.
6-7-96 He had a CT abdomen/pelvis, ="No definite enlarged retroperitoneal
or inguinal lymph nodes.
There is a 1 cm round structure posterior to the right iliac vessels which
could represent a lymph node and should be followed.
6-7-96 Bone Scan: increased activity within the anterior aspect of the
right third rib. This may simply represent a healing rib fracture, although
other etiologies including a metastatic bone lesion could not be excluded.
A small focal zone of increased activity within the upper thoracic spine at
the level of T2-3 may simply represent focally activity degenerative
change, although other etiologies including a metastatic bone lesion could
not be excluded.A comparison x-ray of the right sided ribs and upper
thoracic spine would be helpful.
6-18-96 Research Study report ... Prostate monoclonal antibody report.
Patient injected with 5.36 mCi of Indium-111 Capromab Pendetide and
imaged.. Impression: research study procedure raising concern for recurrent
tumor just inferior to the bifurcation of the right common
iliac vessels and just superior to the prostate bed on the right.
7-2-96 X-ray Right ribs: Multiple views demonstrate no fracture. No
Pneumothorx. No extrapleural soft tissue thickening.
7-2-96 X-ray Thoracic Spine: 2 views demonstrate extensive osteophyte
formation. No evidence of compression fractures or subluxation.
8-15-96 Switched from Lupron to Zoladex and discontinued the Flutamide.
9-15-96 PSA 2.58
6-15-97 PSA 3.00
9-15-97 PSA 3.49
Saw a urologist in Arizona
Your husband's care should ideally be under the guidance of a medical
oncologist specializing in PC.
10-15-97 PSA 1.9
1-15-98 PSA 3.2
4-15-98 PSA 2.5
Ret. to Michigan
5-20-98 PSA 4.3
10-15-98 PSA 1.9
The reason for the fluctuation in PSA from the dates of summer months to
Fall months is the difference in the labs from Michigan to Arizona. For
some reason they are much lower in AZ.
Quest or LabCorp. These are NATIONAL labs and the testing methodology is the
same whether the blood is drawn in a LabCorp or Quest facility in Osgosh or
in Ashland, Oregon.
Arizona
1-15-99 PSA 3.2
4-15-99 PSA 8.0
Michigan
6-15-99 PSA 14.4
Treatment = added Casodex and restarted Lupron
due to the 3 month regimen)
9-15-99 PSA 5.5
Arizona
10-15-99 PSA 3.3
1-15-00 PSA 2.8
Michigan
5-15-00 PSA 3.6
8-8-00 PSA 8.5
Added Proscar
10-2-00 PSA: 10.6
Discontinued Proscar/Casodex started lo-dose DES
1MG daily.
10-4-00 Bone Scan and Ct scans: The bone scans have shown an uptake in the
T -2-3 levels but they have always been described as osteophytes. In 2000
the report stated "most likely related to benign disease."
I like the use of DES but I routinely use 1mg tid with Coumadin or Lovenox
onboard. I also take measures to prevent gynecomastia.
Radiographic correlation may be useful, as neoplasm is not entirely
excluded." CT of Abdomen and Pelvis were always negative.
Arizona
11-15-00 PSA 4.2
2-6-01 PSA 4.3
5-2-01 PSA 4.2
Michigan
5-23-01 PSA 6.1
8-1-01 PSA 6.4
No change in treatment
Arizona
11-8-01 PSA 5.62
2-11-02 PSA 9.52
3-14-02 PSA 6.8
3-28-02 PSA 10.6
I think you have to be grateful for the good years with little significant
change in PSA. However, the studies above indicate that those times are
disappearing. Given the high Gleason score, the PSA also can UNDERstate the
situation regarding tumor volume.
Michigan
5-16-02 PSA 14.1
7-24-02 Had bone scan and MRI of thoracic spine. Result "destructive
lesions involving T3-4 vertebrae. There is a Hx of prostate cancer nd
findings are those of metatastic disease until proven otherwise."
8-12-02 PSA: 19.8
8-16-02 Treatment.. .. Radiation to the spine prescription dose
3500/fraction 250- 14 days.
8-30-02 PSA: 11.3
9-9-02 PSA: 7.9
Arizona
10-31-02 PSA: 2.05
1-20-03 PSA 1.0
4-24-03 PSA 3.4
Michigan
5-16-03 PSA 7.6
Had a bone scan --still describing large osteophyte, but does say
"bone metastasis or uptake of radiopharmaceutical within a tumor is an
additional consideration when given the patients history." CT of
Abdomen/pelvis=No definite findings suggesting metastatic disease.
8-1-03 PSA 18.4
8-22-03 PSA 19.2
Went off DES and started Hi dose Casodex 150 per day. Still on Lupron.
10-1-03 PSA 22.3
Arizona
10-23-03 PSA 13.30
10-30-03 PSA 12.2
11-06-03 MRI Thoracic Spine= metastasis of T3: tumor expands and extends
into the left transverse process. Discussed Zometa injections.
11-18-03 Bone Mineral Density mild irregularity in area of the T3 pedicle.
Rest is negative. Lumbar spine has severe spondylosis of the lower lumbar
spine with some minimal wedging of L 1.
11-21-03 Decision was made for surgery to remove as much of the tumor as
possible after CT and MRI indicated a large tumor almost surrounding the
spinal cord.
The reasoning was to alleviate the possibilty of paralysis, should the
tumor grow. A titanium cage was put in to replace the vertrebrae and
titanium rods and screws to support.
11-24-03 PSA 0.4
They took as much as they could of the tumor and now are prepping for more
radiation to the area, to see if they can keep the cells left from growing.
12-31-03 NM Whole Body Bone scan (Spine Mets) Plain films show no
radiographic abnormality. Show moderate nonspecific tracer accumulation at
T3 which corresponds to the site of prior surgery. There is a curvilinear
area of moderate tracer accumulation extending from the superior left aspect
of this vertebra. Here uptake here is nonspecific and may simply reflect
reactive bone in and area of prior surgery. However, the possibility of
residual neoplasm cannot be entirely excluded. The surrounding upper and
midthoracic vertebra show generally decreased tracer accumulation consistent
with prior radiation therapy.
There are no other sites of abnormal tracer accumulation to suggest
additional osseous metastasis. Degenerative-type uptake is seen in the AC
joints, both knees, left greater than right, and both feet. Renal and
bladder activity within physiologic limits.
1-07-04 Protascint scan MCS
#1 No abnormal uptake around the T3 level to match the findings on recent
bone scintigraphy. Prosthetic devices around the T3 level may limit
evaluation of subtle residual metastasis.
#2 Abnormal ProstaScint uptake within the prostatic fossa from prostatic
carcinoma. Advise correlation with most recent CT exam of the abdomen and
pelvis.
1-10-04 Received injection of Zometa. had bad reaction ... likens it to the
worst case of aching flu ever. Does not want to repeat.
This is called APR or acute phase response and CAN BE AVOIDED by using an
attenuated first dose of Zometa or Aredia.
Adami S, Bhalla AK, Dorizzi R, et al: The acute-phase response after
bisphosphonate administration. Calcif Tissue Int 41:326-331, 1987.
In patients who have never previously received bisphosphonate therapy, the
intravenous administration of 4-amino-1-hydroxybuthilidene
1,1-bisphosphonate (AHButBP)(Alendronate), 3-amino-1-hy-droxypropylidene- 1,
1-bisphosphonate (AHPrBP)(Aredia), or
6-amino-1-hydroxyhexylidene-1,1-bisphosphonate (AHHexBP) induced an
acute-phase response (APR) -irrespective of the underlying disease,
manifested by a fall in circulating lymphocyte number and serum zinc
concentration and in a rise in C-reactive protein (CRP); a febrile reaction
occurred in 30% of the patients. The APR was maximally expressed within
28-36 hours of i.v. administration of the bisphosphonates. And disappeared
2-3 days later despite continuous treatment. These effects were dose
dependent and the lowest doses necessary for an APR were lO mg of AHButBP
and AHPrBP, and 75 mg of AHHexBP. Doses up to 1,000 mg/day i.v. of
dichlormethanebisphosphonate Cl2MBP were devoid of these side effects. In
patients treated with either a single i.v. dose of amino-bisphosphonates
which resulted in an APR or with a suboptimal dose, a subsequent challenge
12-160 days later of the high dose failed to cause a rise in CRP or a fall
in the lymphocyte count. The desensitization to AHButBP or AHPrBP was also
seen following pretreatment with CI2MBP. These findings suggest that
bisphosphonates interact with macrophage-like cells resident in the skeleton
and stimulate interleukin-1 release which is responsible for the appearance
of the APR. At the same time, however, the bisphosphonates render these
cells insensitive to further stimulation for several months. This latter
observation might be relevant to the long-lasting suppression of bone
resorption observed after bisphosphonate therapy.
Since the APR is mediated by release of IL-1, agents that lower IL-1 can
also be used to prevent an APR.
INFO ON dR(down-regulation) of IL-1 beta: (THIS IS A BIG SECTION)
Agents that dR IL-1(senior author):
Curcumin: Jobin
Lipitor: Ascer
Glucosamine: Largo
PTX: Neuner
Indocin: Dash
NDGA: Dash
Nobiletin: Ishiwa
Silymarin: Zhao
TKIs:
Curcumin:
Jobin C, Bradham CA, Russo MP, et al: Curcumin blocks cytokine-mediated
NF-kappa B activation and proinflammatory gene expression by inhibiting
inhibitory factor I-kappa B kinase activity. J Immunol 163:3474-83, 1999.
Department of Medicine, Center for Gastrointestinal Biology and Disease,
University of North Carolina, Chapel Hill 27599, USA. job@med.unc.edu.
NF-kappa B plays a critical role in the transcriptional regulation of
proinflammatory gene expression in various cells. Cytokine-mediated
activation of NF-kappa B requires activation of various kinases, which
ultimately leads to the phosphorylation and degradation of I kappa B, the
NF-kappa B cytoplasmic inhibitor. The food derivative curcumin has been
shown to inhibit NF-kappa B activity in some cell types. In this report we
investigate the mechanism of action of curcumin on cytokine-induced
proinflammatory gene expression using intestinal epithelial cells (IEC).
Curcumin inhibited IL-1 beta-mediated ICAM-1 and IL-8 gene expression in
IEC-6, HT-29, and Caco-2 cells. Cytokine-induced NF-kappa B DNA binding
activity, RelA nuclear translocation, I kappa B alpha degradation, I kappa B
serine 32 phosphorylation, and I kappa B kinase (IKK) activity were blocked
by curcumin treatment. Wound-induced p38 phosphorylation was not inhibited
by curcumin treatment. In addition, mitogen-activated protein kinase/ERK
kinase kinase-1-induced IL-8 gene expression and 12-O-tetraphorbol
12-myristate 13-acetate-responsive element-driven luciferase expression were
inhibited by curcumin. However, I kappa B alpha degradation induced by
ectopically expressed NF-kappa B-inducing kinase or IKK was not inhibited by
curcumin treatment. Therefore, curcumin blocks a signal upstream of NF-kappa
B-inducing kinase and IKK. We conclude that curcumin potently inhibits
cytokine-mediated NF-kappa B activation by blocking a signal leading to IKK
activity.
Lipitor:
Ascer E, Bertolami MC, Venturinelli ML, et al: Atorvastatin reduces
proinflammatory markers in hypercholesterolemic patients. Atherosclerosis
177:6, 2004.
BACKGROUND: Reduction in cardiovascular events with statins has been in part
attributed to their anti-inflammatory properties. OBJECTIVE: Evaluate the
effects of atorvastatin on levels of inflammatory markers, such as tumor
necrosis factor-alpha (TNF), interleukins (IL-1 and IL-6), soluble
intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in
hypercholesterolemic patients (LDL-cholesterol >160 mg/dL). METHODS AND
RESULTS: Two lipid-lowering regimens were taken for 8 weeks. One set of
patients (n=45, 26 men, average 50 +/- 2 years of age) was subjected to
atorvastatin treatment (20-40 mg/day), plus diet recommendation. Another set
of patients (n=23, 12 men, average 53 +/- 3 years of age) went through diet
recommendation alone. Both groups were recommended to perform standard
physical activity. Plasma samples were collected after overnight fasting at
baseline and after 8 weeks for ELISA. The use of atorvastatin when compared
to diet alone, resulted in significant (P <0.0001) reductions for:
LDL-cholesterol (39.9% versus 4.4%), TNF (21.4% versus 2.9%), IL-6 (22.1%
versus 2.0%), IL-1 (16.4% versus 2.7%) and sICAM-1 (9.6% versus 0.1%),
respectively. The percentage of patients with CRP levels >3 mg/dL in the
atorvastatin group fell from 25.0 to 6.7% (P <0.0001) while in the diet
group the reduction was not significant. CONCLUSION: In hypercholesterolemic
patients, atorvastatin, compared to diet alone resulted in significant
reductions in levels of proinflammatory cytokines (TNF, IL-1 and IL-6) as
well as in sICAM-1 and CRP. Thus, statin-induced inhibition of inflammatory
markers may play an important role in the pharmacological and clinical
effects of statins seen in cardiovascular diseases.
Glucosamine:
Largo R, Alvarez-Soria MA, Diez-Ortego I, et al: Glucosamine inhibits
IL-1beta-induced NfkappaB activation in human osteoarthritic chondrocytes.
Osteoarthritis Cartilage 11:290-8, 2003.
OBJECTIVE: Glucosamine sulfate (GS) is a commonly used drug for the
treatment of osteoarthritis. The mechanism of the action of this drug does,
however, remain to be elucidated. In human osteoarthritic chondrocytes (HOC)
stimulated with a proinflammatory cytokine, we studied whether GS could
modify the NfkappaB activity and the expression of COX-2, a
NfkappaB-dependent gene. METHODS: Using HOC in culture stimulated with
interleukin-1 beta (IL-1beta), the effects of GS on NfkappaB activation,
nuclear translocation of NfkappaB/Rel family members, COX-1 and COX-2
expressions and syntheses and prostaglandin E2 (PGE2) concentration were
studied. RESULTS: GS significantly inhibited NfkappaB activity in a
dose-dependent manner, as well as the nuclear translocation of p50 and p65
proteins. Furthermore, GS-preincubated IL-1beta-stimulated HOC showed an
increase in IkappaBalpha in the cell cytoplasm in comparison with HOC
incubated with IL-1beta alone. GS also inhibited the gene expression and the
protein synthesis of COX-2 induced by IL-1beta, while no effect on COX-1
synthesis was seen. GS also inhibited the release of PGE2 to conditioned
media of HOC stimulated with IL-1beta. CONCLUSIONS: GS inhibits the
synthesis of proinflammatory mediators in HOC stimulated with IL-1beta
through a NfkappaB-dependent mechanism. Our study further supports the role
of GS as a symptom- and structure-modifying drug in the treatment of OA.
PTX:
Neuner P, Klosner G, Schauer E, et al: Pentoxifylline in vivo
down-regulates the release of IL-1 beta, IL-6, IL-8 and tumour necrosis
factor-alpha by human peripheral blood mononuclear cells. Immunology
83:262-7, 1994.
Department of Special and Environmental Dermatology, University of Vienna,
Austria
ABSTRACT: Pentoxifylline (PTX) is a methylxanthine compound known to
inhibit the production of tumour necrosis factor-alpha (TNF-alpha), which is
an important inflammatory mediator. There is also recent evidence that PTX
may influence other inflammatory cytokines, such as interleukin-1 (IL-1) and
IL-6. Due to the therapeutic implications, the present study addressed the
in vivo effects of PTX on the release of TNF-alpha, IL-1 beta, IL-6 and IL-8
by human peripheral blood mononuclear cells (PBMC). When PBMC were obtained
from healthy volunteers ingesting 5 x 400 mg PTX orally for 2 days, the
ability of PBMC cultured for 24 hr to release TNF-alpha was significantly
reduced, while secretion of IL-1 beta, IL-6 and IL-8 was not affected.
However, when PBMC were obtained from the same individuals 5 days after PTX
had been stopped, the release of all four cytokines was significantly
suppressed. This effect appeared to be exerted at the transcriptional level,
since Northern blot analysis revealed reduced cytokine transcripts. In order
to gain more insight into the effect of PTX on cytokine release, PBMC were
obtained from normal volunteers, either stimulated with lipopolysaccharide
(LPS) or left unstimulated, and subsequently incubated in vitro with PTX for
48 hr. Under these conditions, only TNF-alpha was found to be reduced by
PTX, while IL-1 beta and IL-8 were not affected, IL-6 was even enhanced.
However, when PBMC were incubated with PTX for 24 hr, PTX removed thereafter
by medium change and cells further cultured, the production not only of
TNF-alpha but also of IL-1 beta, IL-6 and IL-8 was reduced, demonstrating
that PTX exerts diverse (inhibitory) effects on cytokine release by PBMC.
Indocin & NDGA:
Dash PK, Moore AN: Enhanced processing of APP induced by IL-1 beta can be
reduced by indomethacin and nordihydroguaiaretic acid. Biochem Biophys Res
Commun 208:542-8, 1995.
Abnormal processing of the amyloid precursor protein (APP) is thought to
contribute to the formation of amyloid plaques in Alzheimer's disease.
Several studies suggest that inflammation, and possibly the cytokines
released during the inflammatory process, may participate in the plaque
formation. We have utilized a cell culture system to examine the effects of
the cytokine interleukin-1 beta (IL-1 beta) on the processing of APP. We
present data to show that IL-1 beta increases the maturation of APP and
causes enhanced processing of the full length APP isoforms. In addition, as
reported previously in HUVEC cells, IL-1 beta increases the secretion of APP
in PC12 cells. Indomethacin and NDGA, reported inhibitors of the
cyclooxygenase and lipoxygenase pathways, respectively, block these effects,
suggesting the involvement of prostaglandins and leukotrienes in IL-1 beta
mediated APP processing.
Nobiletin:
Ishiwa J, Sato T, Mimaki Y, et al: A citrus flavonoid, nobiletin, suppresses
production and gene expression of matrix metalloproteinase 9/gelatinase B in
rabbit synovial fibroblasts. J Rheumatol 27:20-5, 2000.
OBJECTIVE: Flavonoids including nobiletin are known to exert many biological
actions in vitro. We investigated the chondroprotective effect of citrus
flavonoids, especially nobiletin, using cultured rabbit synovial fibroblasts
and articular chondrocytes. METHODS: We examined the effects of citrus
flavonoids on the production and gene expression of matrix
metalloproteinases (MMP) and prostaglandin E2 (PGE2)production in rabbit
synovial fibroblasts. RESULTS: Six flavonoids isolated from Citrus depressa
Rutaceae including tangeretin, 6-demethoxytangeretin, nobiletin,
5-demethylnobiletin, 6-demethoxynobiletin, and sinensetin suppressed the
interleukin 1 (IL-1) induced production of proMMP-9/progelatinase B in
rabbit synovial cells in a dose dependent manner (<64 microM); nobiletin
most effectively suppressed proMMP-9 production along with the decrease in
its mRNA. Nobiletin also reduced IL-1 induced production of PGE2 in the
synovial cells, but did not modify the synthesis of total protein. These
suppressive effects of nobiletin were also observed in rabbit articular
chondrocytes. Nobiletin inhibited proliferation of rabbit synovial
fibroblasts in the growth phase. CONCLUSION: These results suggest nobiletin
is a novel antiinflammatory candidate that has the potential to inhibit PGE2
production, matrix degradation of the articular cartilage, and pannus
formation in osteoarthritis and rheumatoid arthritis.
Silymarin:
Zhao J, Sharma Y, Agarwal R: Significant inhibition by the flavonoid
antioxidant silymarin against 12-O-tetradecanoylphorbol 13-acetate-caused
modulation of antioxidant and inflammatory enzymes, and cyclooxygenase 2 and
interleukin-1alpha expression in SENCAR mouse epidermis: implications in the
prevention of stage I tumor promotion. Mol Carcinog 26:321-33, 1999.
The flavonoid antioxidant silymarin is used clinically in Europe and Asia
for the treatment of liver diseases and is sold in the United States and
Europe as a dietary supplement. Recently we showed that silymarin possesses
exceptionally high cancer-preventive effects in different mouse skin
carcinogenesis models and affords strong anticancer effects in human skin,
cervical, prostate, and breast carcinoma cells. More recently, we showed
that the anti-tumor-promoting effect of silymarin is primarily targeted
against stage I tumor promotion in mouse skin (Cancer Res 1999;59:622-632).
Based on this recent study, in this report, further investigations were made
to identify and define the biochemical and molecular mechanisms of
silymarin's effect during stage I tumor promotion in mouse skin. A single
topical application of silymarin at 3-, 6-, and 9-mg doses onto SENCAR mouse
skin followed 30 min later with 12-O-tetradecanoylphorbol 13-acetate (TPA)
at a 3-microg dose resulted in a 76-95% inhibition (P < 0.001) of TPA-caused
skin edema. Similarly, these doses of silymarin also showed 39-90%, 29-85%,
and 15-67% protection (P < 0.05 or 0.001), against TPA-caused depletion of
epidermal superoxide dismutase, catalase, and glutathione peroxidase
activity, respectively. Pretreatment of mice with silymarin also produced
highly significant inhibition of TPA-caused induction of epidermal lipid
peroxidation (47-66% inhibition, P < 0.001) and myeloperoxidase activity
(56-100% inhibition, P < 0.001). In additional studies assessing the effect
of silymarin on arachidonic acid metabolism pathways involving lipoxygenase
and cyclooxygenase (COX), similar doses of silymarin showed highly
significant inhibition of TPA-caused induction of epidermal lipoxygenase
(49-77% inhibition, P < 0.001) and COX (35-64% inhibition, P < 0.01 or
0.001) activity. Western immunoblot analysis showed that the observed effect
of silymarin on COX activity was due to inhibition of TPA-inducible COX-2
with no change in constitutive COX-1 protein levels. In other studies,
silymarin also showed dose-dependent inhibition of TPA-caused induction of
epidermal interleukin 1alpha (IL-1alpha) protein (39-72% inhibition, P <
0.005 or 0.001) and mRNA expression. Taken together, the results from these
biochemical and molecular studies further substantiate our recent
observation of silymarin's anti-tumor-promoting effects primarily at stage I
tumor promotion. Furthermore, the observed inhibitory effects of silymarin
on COX-2 and IL-1alpha should be further explored to develop preventive
strategies against those cancers in which these molecular targets play one
of the causative roles, such as non-melanoma skin, colon, and breast cancers
in humans.
1-26-04 Complaining of pain in the area of the surgery (T3). Says it is
muscular feeling, near the shoulder blade along the site of surgery. It is
worse at night so is taking 2 vicodin at night. Had radiation to the area
200 rads to 2000 with IMRT for T2,N2,MO prostate cancer.
2-6-04 PSA 0.5
No treatment change. Still on Lupron and 50mg Casodex.
4-19-04 PSA 0.6
CT Pelvis W contrast: Prostate gland is atrophic likely related to previous
radiation therapy. Small left infuinal hernia containing a loop of sigmoid
colon. No evidence of obstruction, No evidence of metastases in the abdomen
and pelvis.
MICHIGAN
5-27-04 PSA 0.6 Testosterone 38 No treatment change.
8-26-04 PSA 1.2 Testosterone 21
No treatment change.
ARIZONA
12-06-04 PSA 2.91
12-14-04 Whole Body Bone Scan Impression:
1. Degree of uptake at T3 is less than prior exam.
2. Slightly inhomogeneous uptake in lower thoracic spine along the lateral
aspect.
Concern about the lower thoracic on the right side, whether it is
degenerative or osteoarthritic need confirmation on CT scheduled in Jan.
3.No definite new lesions are identified.
4.Increased uptake in the projection of the shoulders and acromioclavicular
joints bilaterally. Knees tarsal bones and ankles compatible with
degenerative and osteoarthritic changes.
Two subtle linear areas of increased uptake noted in the left inguinal
region probably on the basis of urinary contamination.
1-13-05 CT Abdomen & Pelvis
No change from the 4-19-04 CT.
Mild degenerative changes at the costovertebral margins of the T 1 0-12th
ribs. This likely accounts for the mildly increased uptake on the 12-14-04
bone scan. No evidence of metastases.
1-14-05 PSA 6.74
MR Thoracic spine/Lumbar spine/Cervical spine
Nothing to suggest recurrent tumor in the thoracic spine. Some
post-operative changes in the soft tissues dorsal to the thecal sac at
T2,3,4.and at the resection site of the left pedicle and lamina and
transverse process of T3. No central canal stenosis and no evidence of bone
lesions.
Lumbar-there is no evidence of skeletal metastasis in the visualized spine.
Cervical- residual scar from surgery , no evidence of metastasis. It is
impossible to exclude a small amount of recurrent or residual tumor within
the scar tissue of the operative bed, but there is no focal lesion. The
signal in the cord is normal.
2-1-05 BMA
Lumbar spineBl\1D: 1.081 g1cm2 Ll-2).
T -score = +0.3 (S.D.'s from peak bone mass).
Left femoral neck Bl\1D: 0.855 g1cm2.
T -score = -0.6 (S.D.'s from peak bone mass).
Left ultradistal radius Bl\1D: 0.463 g1cm2.
T-score= -1.4 (S.D.'s from peak bone mass).
When compared to 11-18-03 lumbar spine has =1.7% change.
Femoral neck has = +0.4% change.
Ultradistal radius has = -1.5% change.
None of which are statistically significant.
2-17-05 PSA 8.97 Stopped Casodex
3-9-05 PSA 10.98 Prescription for Zocor ..No change in treatment.discussed
Treatment options.
MICHIGAN
5-20-05 PSA 14.6
Dr.did not recommend chemo at this time, due to lack of demonstrative
metatastic disease.
The prostate area appears atrophic; where does the doc in Michigan think the
PSA is coming from?? This is metastatic disease. What is amazing is how long
Julian has gone without the use of chemotherapy. He should be treated with
chemotherapy. He can be tried on HDK first, if so desired.
7-11-05 Had pneumonia-- in hospital over night.
7-28-05 Saw Dr. (Heart) no changes in his meds..
8-16-05 X-ray of thorax for pneumonia
Results: Increased density in right upper lobe. Probably inflammatory.but
neoplasm cannot be excluded.
Thickening of the right paratracheal & paravertebral soft tissues,
upper aspect of the thorax.
9-6-05 PET SCAN. Family MD ordered for lungs.
Results:No suspicious hyper metabolite areas seen in right upper lobe to
suggest malignancy.
Increased uptake in upper thoracic spine most likely due to degenerative
Post surgical changes.
Increased FDG uptake in the large bowel(ascending colon, =inflammatory
changes. Should examine??
9-7-05 PSA 20.6
10-11-05 PSA 40.4 Dr. recommends Taxotere.
ARIZONA
11-02-05 PSA 45.59 Treatment: DES 3mg with coumadin
11-18-05 PSA 33.25 at Mayo Family Clinic
1-3-06 PSA 13.47 still on DES
3-3-06 PSA 8.82 " """
I often recommend a combination of Taxotere PLUS DES with Coumadin on board.
Another combination is Taxotere + Pulse Calcitriol. Another is Taxotere +
Carboplatin =/- DES or Calcitriol.
MICHIGAN
5-4-06 PSA 12.4 Stayed on DES
7-10-06 PSA 17.6 " " "
ARIZONA
10-24-06 PSA 20.83 still on 3mg DES.
Sometimes stopping DES can result in a withdrawal response. Clearly, there
is a need to change therapy.
Saw Dr. and he recommended a clinical trial
The Use of Chemotherapy, Docetaxel (Taxotere),and Prednisone with or without
a Monoclonal Antibody, Bevacizumab, to Treat Men with Prostate Cancer Not
Responding to Hormone Treatments.
That is reasonable.
A CT will be done on Wed. this week..then we will see Dr. for results on
Fri. after Thanksgiving.
11-13-06 Jim in hospital with pneumonia.will probably postpone CT until he
is stronger.
11-21-06 Jim is home from hospital with oxygen as his oxygen level will
not stablize.
Questons:
Would you recommend this clinical trial???
Yes, but Jim has to be off the DES, & the pneumonia completely resolved with
good oxygenation. Of course, my opinion is of limited value without having
seen Jim in person.
Would you recommend ANY clinical trial?/
There is a Taxotere + Vit D trial but I think Jim is not eligible since
prior Taxotere. Check Google using word "Asentar".
Would you suggest other treatments ie...Keto lodose..calcitriol...casodex
150...potential vaccine (trial?)
HDK(high-dose ketoconazole) or Nizoral at standard dose is my choice. I am
not in favor of using the lower dose regimen in light of what I have
personally seen over 20 years using the standard HDK regimen. Read about
this in http://prostate-cancer.org/resource/pdf/Is4-3.pdf or obtain a copy
of the full paper from J of Urology:
Scholz M, Jennrich R, Strum S, et al: Long-term outcome for men with
androgen independent prostate cancer treated with ketoconazole and
hydrocortisone. J Urol 173:1947-52, 2005. PMID 15879788
PURPOSE: The combination of high dose ketoconazole and hydrocortisone (HDK)
is active against androgen independent prostate cancer (AIPC). Median
response times with HDK tend to be brief but a significant minority of AIPC
patients benefit with extended responses. Well characterized response and
survival information, especially in the cohort of patients who experience
these longer, more durable, responses has not been previously reported.
Characterization of this subgroup is of particular interest since men with
long-term responses derive the greatest benefit from HDK therapy. MATERIALS
AND METHODS: The medical records of 78 patients with AIPC treated with HDK
between March 1991 and February 1999 were retrospectively reviewed. Baseline
clinical and laboratory factors predictive of prolonged response and
survival were identified. RESULTS: The median baseline prostate specific
antigen (PSA) before the initiation of HDK was 25.1. The number of patients
with zero, 1 to 3, and more than 3 lesions on bone scan were 25, 35 and 18,
respectively. Median and mean time to PSA progression was 6.7 and 14.5
months. Median and mean survival time was 38.0 and 42.4 months,
respectively. Response time and survival were highly correlated (r = 0.799).
A total of 34 (44%) men had a greater than 75% decrease in PSA. The median
survival times in men with more vs less than a 75% decrease were 60 vs 24
months, respectively. In a Cox proportional hazard regression, prolonged
survival was predicted by percent PSA decrease, extent of disease on bone
scan and baseline PSA. CONCLUSIONS: Ketoconazole can induce prolonged
responses, occasionally lasting for years. Long responses are more likely to
occur in men initiating HDK earlier in the course of disease before the
cancer burden becomes excessive.
cytoxan/predisone other???
There are a number of regimens that involve other chemo agents. A
comprehensive list is shown below:
Taxotere + Carbo + Celebrex
Taxotere + Calcitriol 0.5mcg/kg
Taxotere + Gleevec
Taxotere + Clusterin ASO
Taxotere + Revamid (clinical trial via CTRC.com)
Taxotere + Gemzar (alternate is Taxol alternating weekly with Gemzar)
Taxotere + Capecitabine
Taxotere + Velcade + Gleevec
Cytoxan + 5-FU + DES + Coumadin (Servadio Regimen)
Cytoxan + DES + Coumadin
Leukine + Thalidomide (Leukine dose is 250mcg 4 times per week; Thalidomide
is 100mg/hs); Lovenox suggested to prevent thrombosis
Leukine + Accutane or ATRA
EE + Lanreotide ( ethinylestradiol (EE) is not supposed to cause
thrombosis; would use anti-coagulant)
DXM + Lanreotide Q 2wks vs Q wk (Koutsilieris Regimen)
HDK + HC
HDK + Triamcinolone
HDK + Adria
HDK + Adria + Velban + Emcyt + Coumadin
Mitoxantrone + Prednisone
2C4
Atrasentan vs Bosentran
Avastin + Taxotere or another chemo combination
Velban + Mitomycin C weekly (low dose for each drug)
Oral
Cytoxan
Xeloda
Etoposide
IV
Taxotere
Taxol
Carboplatin (paraplatin)
Cisplatin
Abraxane
Adriamycin (doxorubicin)
Novantrone (Mitoxantrone)
Navelbine
Velban
Mitomycin C
5-FU
Cytoxan
Vincristine
Gemzar (gemcitabine)
Etoposide (VP-16)
Taxol or Taxotere followed 24 hrs later by Carboplatin
Taxane followed by 5-FU
Adriamycin (24 hr infusion) followed by Zometa (one hour infusion)
Gemzar followed by 96hrs then Taxotere
Adriamycin followed by Taxol, then 48hrs washout, then Gemzar (24hr
infusion)
Adriamycin(4hr infusion) followed by Taxol (24hr infusion)
I have heard/read several comments about trying ALL other treatments before
going to chemo...
you thoughts?...
I think Jim has seen just about all major approaches with the exception of
HDK(high-dose ketoconazole) or Nizoral.
The Dr. we see here at Mayo clinic is in Hematology/oncology, but his field
is Interests:Lymphoma,Breast Cancer, Bone Marrow Transplantation,
Castleman's Disease, Myeloproliferative Disorders.
It seems none of them here are "PC" specialists..
That's why I entered this field many years ago--a huge need for this. You
may wish to get another opinion but first ask your local MD if he will work
with a medical oncologist specializing in PC from a distance. You could get
started on a program and then follow it up locally.
Names of medical oncologists with full practice offices:
Mark Scholz,& Richard Lam, MDs
Prostate Oncology Specialists
4676 Admiralty Way, Suite 101
Marina del Rey, CA 90292
T:310-827-7707
F:310-574-4002
Glenn Tisman MD Inc.
13025 Bailey Street
Whittier, CA 90601
T: 562-789-8822
F: 562-698-4582
E: gtisman@doctisman.com
Steven Tucker, M.D.
Director, Prostate & GU Oncology Program
The Angeles Clinic & Research Institute
11818 Wilshire Blvd., Suite 200
Los Angeles, CA 90025
T: 310.231.2121
F: 310.231.2172
E: stucker@theangelesclinic.org
W: www.theangelesclinic.org
M: 310-266-3380
(Tucker is now in Singapore)
Bob Leibowitz, M.D.
Compassionate Onc Medical Group
2080 Century Park E
Suite 1005
Los Angeles, CA 90067-2009
T: 310-229-3555
F: 310-229-3554
francine@compassionateoncology.org
Myers and I only do consultations; we do not have full service offices
regarding administration of chemotherapy.
Charles "Snuffy" Myers, MD
American Institute of Disease of the Prostate &
Foundation for Research and Education
P.O. Box 307
Free Union, VA 22940
960 Bent Oaks Drive (Office)
Earlyville, VA 22936
434-964-0212
Fax: 434-964-0216
snuffym@aol.com
Contact: Rose Myers.
rosemyers@earthlink.net
Stephen B. Strum, MD, FACP
538 Granite Street
Ashland, OR 97520
T: (O) 541-201-0219
Fax 541-482-1284
stephen@sbstrum.com
I have extremely strict conditions re: the patients who I accept. Given
this, and the complexity of Jim's case, and my current work load, I would
suggest one of the other docs listed above. I wish you well.
If the above has been helpful to you, consider a tax-deductible donation to
the PCRI (Prostate Cancer Research Institute). Note that I am no longer
affiliated with that organization but it is the best one to provide help to
the man with PC.
Stephen B. Strum MD, FACP
Medical Oncologist Specializing in Prostate Cancer
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