Treatment of poor prognosis germ cell tumours with high dose cisplatin regimens

We have developed an intensive combination chemotherapy regimen for the treatment of patients with poor risk nonseminomatous testicular cancer. This regimen (termed PVeBV) consists of cisplatin [P] (at twice the dose used in previous combination chemotherapy regimens), vinblastine [Ve], bleomycin [B], and VP-16 [V]. Cisplatin was administered in hypertonic saline with vigorous chlorouresis. In a pilot study we demonstrated that PVeBV was an active regimen in high risk patients but associated with severe myelosuppression. Consequently, a clinical trial of PVeBV vs standard PVeB chemotherapy in high risk patients is currently in progress at the Medicine Branch of the National Cancer Institute. Patients eligible for this trial must be previously untreated and have bulky disease either in the abdomen or lungs as well as other poor prognostic features. A preliminary analysis of this trial demonstrates a higher complete remission rate (87%) for PVeBV compared to (62%) for PVeB. There has only been one relapse (4%) in patients randomized to receive PVeBV compared to a 20% relapse rate in patients receiving PVeB. There is no statistically significant increase in survival for patients randomized to PVeBV; however, there is a statistically significant prolongation of disease-free survival in patients receiving the intensive four-drug regimen. The increased toxicity of PVeBV was due primarily to more severe myelosuppression. These results demonstrate that PVeBV chemotherapy can be administered to high risk testicular cancer patients with acceptable toxicity and that the preliminary analysis of a randomized trial suggests that PVeBV may be superior to PVeB in the treatment of these high risk patients.