Birch R

Treatment of Disseminated Germ-Cell Tumors with Cisplatin, Bleomycin, and either Vinblastine or Etoposide

Standard chemotherapy for disseminated germ-cell tumors includes a combination of cisplatin, vinblastine, and bleomycin, but this regimen produces substantial neuromuscular toxicity. In a randomized clinical trial in 261 men with disseminated germ-cell tumors, we substituted etoposide for the vinblastine in this regimen in half the patients to compare the efficacy and toxicity of the two treatments. Among 244 patients who could be evaluated for a response, 74 percent of those receiving the regimen including vinblastine and 83 percent of those receiving the regimen including etoposide became disease-free with or without subsequent surgery (P not significant). Among the 157 patients with high tumor volume, 61 percent became disease-free on the regimen that included vinblastine, as compared with 77 percent on the regimen that included etoposide (P less than 0.05). Survival among the patients who received etoposide was higher (P = 0.048). The regimens were similar in terms of myelosuppressive effects and pulmonary toxicity. However, the etoposide regimen caused substantially fewer paresthesias (P = 0.02), abdominal cramps (P = 0.0008), and myalgias (P = 0.00002). We conclude that etoposide with cisplatin and bleomycin is superior to vinblastine with cisplatin and bleomycin in the treatment of disseminated germ-cell tumors because of diminished neuromuscular toxicity and, among patients with advanced disease, better efficacy.

Evaluation of optimal duration of chemotherapy in favorable-prognosis disseminated germ cell tumors: a Southeastern Cancer Study Group protocol.

Four courses of PVP16B (cisplatin plus etoposide [VP-16] plus bleomycin) has been standard chemotherapy for disseminated germ cell tumors at Indiana University and the Southeastern Cancer Study Group (SECSG) since 1984. We began a random prospective phase III study in patients with favorable-prognosis (minimal and moderate extent) disseminated germ cell tumors comparing four courses of PVP16B over 12 weeks to the identical dose PVP16B administered in three courses over 9 weeks. The categories of minimal and moderate disease constitute approximately two thirds of all disseminated germ cell tumors that require chemotherapy. One hundred eighty-four patients entered this trial, and all patients have a minimal follow-up of 1 year. Overall, 106 of 107 (99%) minimal extent and 73 of 77 moderate patients (95%) achieved an initial disease-free status (NED), confirming the favorable prognostic categories. Eighty-six of 88 patients (98%) randomized to three courses and 93 of 96 randomized to four courses (97%) of PVP16B achieved disease-free status. There have been ten relapses (5%), with five on each arm. Currently, 81 of 88 (92%) and 88 of 96 (92%) patients randomized to three v four courses of PVP16B are continuously disease-free. This study confirms the high cure rate with PVP16B in favorable-prognosis germ cell tumors. The deletion of the fourth course of PVP16B significantly reduces the toxicity, cost, and inconvenience of this curative regimen. We conclude that three courses of PVP16B is the preferred regimen for favorable-prognosis germ cell tumors.

Chemotherapy of Metastatic Seminoma: The Southeastern Cancer Study Group Experience

From 1978 to 1984, 62 patients with advanced seminoma of testicular or extragonadal origin were entered on two consecutive Southeastern Cancer Study Group (SECSG) protocols. All patients had progressive disease and were stratified according to tumor burden. Randomization on SEG 78-GU240 was cisplatin, vinblastine, and bleomycin (PVB), with or without doxorubicin; on SEG 81-GU332, randomization was to PVB or cisplatin, etoposide (VP-16), and bleomycin (PVP16B). Dosages of etoposide, vinblastine, and doxorubicin were decreased by 25% in patients who had received prior radiotherapy. Thirty patients (55%) had received prior chest and/or abdominal radiotherapy. Overall, 41 of 60 evaluable patients (68%) achieved a complete remission (CR) and 37 patients are alive and free of disease. CR was obtained in 13 of 15 patients (87%) with minimal disease, 13 of 16 (81%) with moderate disease, and 15 of 29 (52%) with advanced disease. Patients with no prior radiotherapy or limited-field (chest or abdomen) radiotherapy were more likely to achieve CR than those with prior chest and abdominal radiotherapy (75% v. 42%). Using univariate analysis, the extent of disease is the only significant prognostic factor, whereas both extent of disease and extent of prior radiotherapy are significant in a multivariate analysis. This study confirms the chemosensitivity of metastatic seminoma in a cooperative group setting and defines prognostic factors useful for comparison of other chemotherapeutic trials in seminoma.