PCRI Attends 3rd PC Symposium in Orlando

See also: Synopsis of the 2007 Prostate Cancer Symposium

PCRI was well-represented at The Prostate Cancer Symposium - A Multidisciplinary Approach in Orlando FL (Feb. 22-24, 2007). The full Helpline staff of Harry Pinchot, Jan Manarite and Jim O’Hara attended many of the sessions and had an exhibit highlighting PCRI services. Executive Director Mark Scholz, MD and Chief Operating Officer Joe Bueno were also in attendance promoting PCRI and our September conference.

The 2007 Prostate Cancer Symposium featured over 60 talks and more than 400 poster presentations by prominent physicians and scientists. The symposium had an attendance of 1600 specialists in prostate cancer from around the world. It was co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Therapeutic Radiology and Oncology (ASTRO) and the Society of Urologic Oncology (SUO). The conference “Needs Statement” highlights the importance of this meeting.

" A number of recent studies demonstrate that novel treatments may improve the care of patients with prostate cancer. Other new studies shed light on which patients may benefit from the most aggressive therapy. With the arrival of exciting new agents including vaccines, monoclonal antibodies, bone-targeted therapies and others, the future treatment of prostate cancer appears promising. Furthermore, translational and clinical research on prostate cancer is ever advancing, and it is probable that in the near future, novel strategies will become available for both prostate cancer risk assessment and targeted management. These multiple ongoing, parallel lines of research promise to improve the current standard of care in terms of screening efforts, diagnosis, risk stratification, and primary management. To properly identify and manage patients with prostate cancer, physicians must have an in-depth understanding of the treatment options and stay abreast of the rapid evolution of prostate cancer management.”

A couple of underlying themes seemed to echo through the event that patients with “low-risk” prostate cancer are over-treated while “high-risk” patients lack the treatments that can provide long-term control. However, many novel therapies are being evaluated that may provide successful combinations of therapy.

This report will highlight some areas that we found to be of particular interest. The audio and the slides for the full three days of talks, along with most of the 416 abstracts, are available on the ASCO website. A synopsis of many of the presentations by Dr. Scholz will be published in the May 2007 issue of PCRI Insights.

Active Surveillance

Several speakers suggested the use of the 2003 Kattan nomogram for the “probability of indolent cancer” as part of their analysis in recommending active surveillance. This nomogram was discussed in the Nov 2005 issue of PCRI Insights.

Active Surveillance in Low-Risk Disease: Who Doesn't Need Treatment? Chris Parker, MD, from Royal Marsden (UK) Active surveillance is a reasonable treatment for men with T1/T2a disease, Gleason = 3+4 and PSA < 15

Active Surveillance in Low-Risk Disease: Who Does Need Treatment? Peter Scardino, MD of Memorial Sloan-Kettering stated they recommend use of the Kattan nomogram but caution patients that 27-35% of biopsies underestimate the Gleason score, a third of the patients who die of prostate cancer are Gleason = 6 and younger patients that qualify may have a life-expectancy of 20-30 years with risk of progression. They monitor patients with a schedule of PSA tests, DRE’s and biopsies.

The Role of PSA in Screening and Early Detection of Prostate Cancer Fritz H. Schröder, MD, PhD from Erasmus (Netherlands) mentioned that if the Kattan nomogram had been applied to all cancers diagnosed in a Rotterdam study, 29% would have had a 70% probability of indolent tumors and could have been safely included in active surveillance studies.

Is Active Surveillance an Opportunity for Tertiary Prevention? Neil Fleshner, MD from Univ of Toronto defined “tertiary prevention” as halting disease progression. Active surveillance is an ideal time for lifestyle modifications like diet, exercise, smoking cessation, and control of cholesterol and hypertension. He suggested possible benefit of lycopene, vitamin E, selenium and green tea extract. Another option could be the use of 5-alpha reductase inhibitors which would have an added benefit of dampening PSA spikes that often cause patient anxiety. This is being investigated in a clinical trial called “REDEEM”.

Pathological characteristics, disease free survival, and quality of life (Qol) of patients treated by radical prostatectomy (RP) who might have been elected for active surveillance. Abstract 333 Tombal reported “We considered indolent PCa those with all the following criteria: stage T1c/T2a, one single positive sextant, Gleason score <6, PSA < 15 ng/ml, PSA density < 0.20 ng/(ml × cc). … Indolent PCa were retrospectively identified in 97 (33%) patients. … No patients had positive lymph nodes. RP's Gleason score was < 6 in 89% and 7 in 11% of indolent PCa, while no Gleason 8 was detected. … Forty-eight months after surgery, 51% of the patients were still fully continent while 45% reported little urine leakage; 33% had sexual intercourse within the last months but 72% still experienced difficulties in obtaining erections.”

New Options for Advanced Prostate Cancer

Many of the talks and posters describe novel therapies that are being tested in clinical trials in combination with or in contrast to docetaxel (Taxotere®).

Characterization of a new anti-androgen MDV-3100 effective in preclinical models of hormone refractory prostate cancer. Charles Sawyers, MD gave an exciting talk on work done while at UCLA to develop an antiandrogen that remains effective in cells expressing a high level of androgen receptor and does not acquire an agonist property like current antiandrogens. MDV3100 has shown in mouse studies with cancer cells expressing high AR to reduce tumor volume by up to 68% from baseline vs. Casodex which resulted in a 37% increase. Clinical trials are expected to start this year. MDV3100 has shown to be 10x more potent than Casodex in multiple HRPC models.

Combination immunotherapy with GM-CSF and ipilimumab (anti-CTLA4 antibody) in patients with metastatic hormone refractory prostate cancer. Abstract 49 Small et al reported “of 6 patients treated on the highest dose level (3.0 mg/kg ×4), 3 (50%) have had PSA declines of >50%, and one of these patients had a partial response in hepatic metastases”. They concluded “CTLA-4 blockade and GM-CSF have demonstrated activity in advanced prostate cancer pts”.

Phase I evaluation of abiraterone acetate (CB7630), a 17-alpha hydroxylase C17,20-lyase inhibitor in androgen-independent prostate cancer (AiPCa). Abstract 278 Ryan et al reported “overall, 6 of 6 (100%) pts who completed a 28-day treatment cycle have experienced a decline in PSA, and 5 of 6 patients (83%) experienced a > 50% decline in PSA”.

Activity, toxicity, and effect on steroid precursor levels of abiraterone (A), an oral irreversible inhibitor of CYP17 (17a hydroxylase/17,20 lyase), in castrate men with castration refractory prostate cancer (CRPC) Abstract 264 Attard et al reported “No dose-limiting toxicity has been observed…a 50% PSA decline in 70%, PSA declines of >90% in 50%, and radiological partial responses in 50% of pts”

A phase III, randomized, double-blind trial of satraplatin and prednisone vs placebo and prednisone for patients with hormone refractory prostate cancer (HRPC). Abstract 145 Petrylak et al reported “in 950 patients with hormone-refractory prostate cancer (HRPC) who have failed prior chemotherapy - an 89% improvement in progression-free survival (36 vs 19 wks) … The most common toxicities were … generally mild to moderate.”
Special note: GPC Biotech announced at the Symposium that, for a limited time, they are making available to U.S. investigators, an “expanded access” program for Satraplatin. For more info

Phase II trial of combination low-dose flutamide plus finasteride versus low-dose flutamide monotherapy for biochemical recurrence following definitive therapy for prostate cancer: Long-term follow-up Abstract 194 Moul et al reported “Men on combination therapy experienced a significantly greater drop in their PSA and had a higher proportion of men (36% vs. 15%) exhibit a complete response to therapy.”

Randomized phase II study of docetaxel with or without DMXAA (AS1404) in hormone-refractory metastatic prostate cancer (HRMPC). Abstract 219 Rosenthal et al reported “Addition of DMXAA to standard-dose docetaxel was well tolerated and the combination produced a substantially higher PSA response rate than docetaxel alone (response of =50% were achieved by 57% of the patients on DMXAA vs 35% on docetaxel alone)”

Phase II trial of thalidomide, bevacizumab, and docetaxel in patients (pts) with metastatic androgen-independent prostate cancer (AIPC). Abstract 228 Ning et al reported “33 pts were enrolled, median age 67 [54-79], Gleason score 8 [76% Gs 10~8, 24% Gs 7~6], on-study PSA 87 ng/ml [7.7-4,399] and pre-study PSA doubling time 1.6 months … 28 pts (85%) had PSA declines of >50%, 23 pts (70%) had >80% PSA declines”

Phase II trial of docetaxel and capecitabine combination in metastatic androgen independent prostate cancer (AIPC) Abstract 239 Vaishampayan et al reported “A PSA partial response (PR) defined as > 50% decline sustained for at least 4 weeks was observed in 19/27 (71%) with >90% PSA decline in 8/27 (30%) patients.”

Activity of dustasteride plus ketoconazole in hormone-refractory prostate cancer (HRPC) after progression on ketoconzole alone Abstract 257 Sartor et al reported “Dutasteride in combination with ketoconazole is associated with delays in PSA progression in HRPC patients experiencing PSA progression after ketoconazole alone.”

Miscellaneous Items

Emerging Assays: Circulating Tumor Cells Robert Vessella PhD from Univ. of Washington, discussed the potential of using Circulating (in blood) and Disseminated (in bone or lymph node) Tumor Cells (CTC&DTC) to develop assays to predict recurrence and identify therapeutic targets. He remarked that DTC’s have been found in dormant state over 10 years past local treatment but some may later result in clinical metastases. CTC and DTC could be detected in 25-80% patients at time of diagnosis. New technologies allow samples with few CTC’s to be enriched and analyzed.

Outcome Prediction Models Kevin Slawin, MD of Baylor mentioned that Hybritech/BCI PSA assay results are reproducibly 23% higher than that of all other assays, including Bayer, Cenntaur, DPC, etc. He also mentioned a 20% biological variation in PSA of men with a prostate but minimal biological variation in men without a prostate.

PSA density as a predictor of aggressive prostate cancer on repeat prostate biopsy Shane Rogosin, MD of Oregon Health & Science University concluded that a high PSA Density is predictive of aggressive prostate cancer on a repeat biopsy and a PSADT < 2 yrs becomes the most significant predictor of aggressive cancer.

Treatment-Related Diabetes and Cardiovascular Disease: Are Some Men Dying for a Lower PSA? Matthew Smith, MD, PhD of Massachusetts General stated that about one-third of the two million prostate cancer survivors in the U.S. currently receive treatment for androgen deprivation (ADT). He discussed impacts of ADT including the increase of fat mass, artficerial stiffness, insulin levels, cholesterol and lipid levels. ADT is signiantly associated with greater risk of diabetes and cardiovascular disease.

Toremifene citrate increases bone mineral density in men receiving androgen deprivation therapy for prostate cancer. Abstract 149 and Effect of toremifene on total cholesterol, LDL, triglycerides, and HDL in men receiving androgen deprivation therapy for advanced prostate cancer Abstract 150 Smith et al reported “In a 24-month prospective study, 1,392 men with prostate cancer who have been treated with ADT for at least 6 months and are at increased risk of fracture … toremifene citrate significantly increased BMD of the hip and spine” and “Toremifene decreases total cholesterol, LDL cholesterol, and triglycerides and increases HDL cholesterol in men receiving ADT for advanced prostate cancer compared to placebo.”

Chromogranin A expression in needle biopsies of hormone-sensitive prostate cancer patients predicts the development of hormone-refractoriness Abstract 224 Mosca et al reported “Tissue CgA expression, revealed in biopsies of newly diagnosed PC patients undergoing androgen suppression therapy, is an independent predictive factor of hormone refractory disease. Moreover, circulating CgA is a reliable predictive marker, and its predictive significance is maintained over time.”

 

Prostate Cancer Research Institute (PCRI)
 

Material provided by PCRI is intended for educational purposes for discussion with your physician and should not be considered as medical advice. Information and opinions expressed on this website are not an endorsement by PCRI for any treatment, product or service.