Intensive induction chemotherapy with C-BOP/BEP for intermediate- and poor-risk metastatic germ cell tumours (EORTC trial 30948).

New chemotherapy regimens are continuously explored in patients with high-risk malignant germ cell tumours (MGCTs). This multicentre phase II trial assessed the efficacy and toxicity of C-BOP/BEP chemotherapy in intermediate and poor prognosis MGCT (IGCCCG criteria). C-BOP/BEP treatment consisted of cycles of cisplatin, vincristine, bleomycin and carboplatin, followed by one cycle of vincristine and bleomycin and three cycles of BEP (bleomycon, etoposide, cisplatin). The trial was designed to demonstrate a 1-year progression-free survival rate of 80%, that is, to exclude a 1-year rate of 70% or less, with a one-sided significance level of 5%. Secondary end points included toxicity, overall survival and the postchemotherapy complete response rate. In total, 16 European hospitals entered 66 eligible patients (intermediate prognosis group: 37; poor prognosis group: 29). A total of 45 patients (68.2%, 95% confidence interval (95% CI): 56.9-79.4%) achieved a complete response (intermediate prognosis: 30; poor prognosis: 15). After a median observation time of 40.4 months (range: 13.7-66.3), the 1-year progression-free survival rate was 81.8% 95% CI: 72.5-91.1%). The 2-year overall survival was 84.5% (95% CI: 75.6-93.3%). In all, 51 patients experienced at least one episode of WHO grade 3/4 leucopenia, and at least one event of grade 3/4 thrombocytopenia occurred in 30 patients. There was no toxic death. With an 82% 1-year progression-free survival and a lower limit of the 95% CI above 70%, the efficacy of C-BOP/BEP is comparable to that of published alternative chemotherapy schedules in high-risk MGCT patients. The treatment's toxicity is manageable in a multicentre setting. In poor prognosis patients, C-BOP/BEP should be compared to standard chemotherapy of four cycles of BEP.

Phase III trial of satraplatin, an oral platinum plus prednisone vs. prednisone alone in patients with hormone-refractory prostate cancer.

Satraplatin is a novel oral platinum (IV) complex that shows activity against hormone-refractory prostate cancer (HRPC) in cisplatin-resistant human tumor lines in phase I and phase II trials. A randomized multicenter phase III trial with a target sample size of 380 patients was initiated in men with HRPC. After 50 randomized patients, the trial was closed to further accrual by the sponsoring company. An ad hoc analysis of all available data is reported here. Eligibility criteria included pathological proof of prostate cancer, documented progression despite prior hormonal manipulation, WHO PS 0-2, and no daily intake of narcotic analgesics. Patients were randomized between satraplatin 100 mg/m(2) for 5 days plus prednisone 10 mg orally BID or prednisone alone. Compliance was excellent. 48/50 patients have progressed and 42 have died, mostly due to prostate cancer. Median overall survival was 14.9 months (95% CI: 13.7-28.4) on the satraplatin plus prednisone arm and 11.9 months (95% CI: 8.4-23.1) on prednisone alone (hazard ratio, HR = 0.84, 95% CI: 0.46-1.55). A >50% decrease in prostrate specific antigen (PSA) was seen in 9/27 (33.3%) in the satraplatin plus prednisone arm vs. 2/23 (8.7%) on the prednisone alone arm. Progression-free survival was 5.2 months (95% CI: 2.8-13.7) on the satraplatin plus prednisone arm as compared to 2.5 months (95% CI: 2.1- 4.7) on the prednisone alone arm (HR = 0.50, 95% CI: 0.28-0.92). This difference is statistically significant (p = 0.023). Toxicity was generally minimal in both arms. This randomized comparison of a combination of satraplatin and prednisone versus prednisone alone supports the antitumor activity of the combination. Its role in the treatment of HPRC remains to be elucidated in an appropriate phase III setting.

Residual mass following chemotherapy of seminoma.

BACKGROUND: The residual mass so frequently found after chemotherapy of advanced seminoma may consist entirely of benign tissue or may contain residual disease amenable to adjuvant therapy. PATIENTS AND METHODS: A detailed retrospective analysis was performed on 45 patients treated with cisplatin based chemotherapy for advanced seminoma between 1978 and 1994. RESULTS: The probability of a residual mass after chemotherapy was higher if the pre-treatment mass diameter was > 5 cm (78% versus 15%, P = 0.0009). Of 33 patients with residual masses following cisplatin chemotherapy, 4 were explored surgically showing fibrosis only, 15 were treated by adjuvant radiotherapy and 14 were managed by observation alone. Recurrence occurred in 2 of 14 patients managed by observation and in 2 of 15 managed by radiotherapy. There was no evidence that risk of recurrence was related to diameter of residual mass. CONCLUSION: Residual masses persisted following cisplatin based combination chemotherapy for seminoma in 73% of cases. In our study, recurrence was rare and there was no evidence that this was influenced by either the size of the residual mass or the use of adjuvant therapy.