the impact of nerve sparing on risk for positive surgical margins and biochemical progression
combination therapy with external beam radiation and high-dose, conformal brachytherapy for high risk, localized disease
a negative trial of fulvestrant (Faslodex®) in hormone resistant prostate cancer
initial survival data from an early poxvirus-based PSA vaccine trial compared to antiandrogen therapy, and
an early-stage trial of docetaxel + temozolomide in patients with refractory, metastatic solid tumors (not just prostate cancer).
Nelles et al. have examined data from 1,018 men who received radical prostatectomies (RPs) between 1988 and 2006 at five centers participating in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. They report that neither bilateral nor unilateral nerve-sparing techniques were associated with a higher risk of positive surgical margins (PSMs). They also report that risk for biochemical recurrence was not affected by bilateral or unilateral nerve sparing. They coinclude that, when used on appropriately selected patients, nerve sparing does not increase the probability of PSMs or biochemical recurrence after RP.
Prada et al. have provided detailed 8-year outcome data from their study of local dose escalation using high-dose-rate conformal brachytherapy (HDRCB) combined with external beam radiation therapy (EBRT) for patients with high-risk prostate cancer. Between June 1998 and June 2007, they enrolled 134 patients with high-risk, localized prostate cancer. Median follow-up was 45 months. Patients were considered to be eligible for the study if they met one or more high risk criteria (PSA ≥ 20 ng/mL and/or Gleason > 7 and/or stage ≥ T3a) or two intermediate-risk criteria (PSA 11-19 ng/mL, Gleason 7, stage T2b-c). The total dose of EBRT was 46 Gy in 200-cGy daily fractions. HDRCB was performed at the end of weeks 1 and 3 of the 5-week radiotherapy course. The dose administered at each application was 1,150 cGy. Mean follow-up for the entire group was 45 months. Estimated overall survival was 85 ± 5 percent at 5 and at 8 years. Estimated biochemical progression-free survival was 80 ± 4 percent at 5 years and 73 ± 7 percent at 8 years. The 8-year prostate cancer-specific mortality was 10 ± 4 percent. Low rates of adverse reactions to treatment are also reported. The authors believe that their data confirm the feasibility and effectiveness of EBRT with a HDRCB boost for patients with high-risk prostate cancer.
Negative clinical trial results are often not published, so it is always good when they are. Chadha et al. have just published a report on the tolerability and efficacy of fulvestrant, a pure estrogen receptor antagonist, in the treatment of castration resistant prostate cancer (CRPC). They concluded that fulvestrant was well tolerated but failed to produce clinical or PSA response in men with CRPC.
Madan et al. have reported on survival data from their study comparing a poxvirus-based PSA vaccine, the hormone nilutamide, and the combined therapy (crossover for each arm) in patients with non-metastatic, castrate-resistant prostate cancer CRPC). Forty-two patients were randomized to receive either the PSA vaccine or nilutamide. Patients who developed increasing PSA without radiographic evidence of metastasis could cross over to receive the combined therapies. Median survival among all patients was 4.4 years from date of enrollment. Median survival exhibited a trend toward improvement for patients initially randomized to the vaccine arm (5.1 vs 3.4 years; P = 0.13). Starting from the on-study date, the retrospectively determined subset of 12 patients who initially received vaccine and then later received nilutamide appear to have improved survival compared with the eight patients who began with nilutamide and subsequently were treated with vaccine (median survival, 6.2 vs 3.7 years; P = 0.045). A subgroup analysis of patients randomized to the vaccine arm versus the nilutamide arm showed substantial improvements in survival if at baseline patients had a Gleason score < 7 (P = 0.033) and PSA < 20 ng/dL (P = 0.013) or prior radiation therapy (P = 0.018). The authors conclude that patients with non-metastatic CRPC who receive vaccine before second-line hormone therapy may potentially have improved survival compared with patients who received hormone therapy and then vaccine. They also state that that patients with more indolent disease may derive greater clinical benefit from vaccine alone or vaccine before second-line hormone therapy compared with hormone therapy alone or hormone therapy followed by vaccine. This trial is clearly a study involving small numbers of patients, and larger trials would be needed to substantiate the data offered by this study.
Tamaskar et al. have investigated the toxicity of docetaxel and temozolomide in 25 patients with refractory, metastatic, solid tumors, including prostate cancer. Docetaxel was administered weekly in five escalating doses of 25 to 35 mg/m 2; as a 1-hr infusion for 3 consecutive weeks. Temozolamide was administered orally daily for 3 weeks at escalating doses of 75 to 100 mg/m 2. Cycles were repeated at 4 week intervals. The authors report that the maximum tolerated dose of the combination was not determined in this study. Commonly reported adverse events were mild to moderate nausea, vomiting and fatigue. Thrombocytopenia was the most commonly observed grade 3 and 4 hematological toxicity. Two patients achieved partial responses and 88 percent of the patients have died. The median survival was 8.4 months. They conclude that the combination of docetaxel and temozolomide was well tolerated and these agents can be safely combined. They further recommend that, for phase II trials, doses of docetaxel 35 mg/m 2 IV on days 1, 8 and 15, and daily temozolomide at 100 mg/m 2 on days 1-21 are investigated.