Phase II Study of Paclitaxel and Gemcitabine ‘Salvage’ Chemotherapy for Germ Cell Tumours that are Uncontrolled with High Dose Chemotherapy Following Tandem Transplants

A recent article published in the Journal of Clinical Oncology presented a retrospective review of the durable remission and potential cure of patients with germ cell tumours when treated with salvage chemotherapy. Study participants had also previously undergone cisplatin combination chemotherapy and high dose chemotherapy with tandem transplantation, which had been unsuccessful at controlling the progression of disease. A sample size of 32 patients was studied, and 10 of these demonstrated an objective response to therapy. There were four partial remissions among participants, lasting less than six months; and six complete responses, the longest of which has been recorded as being completely disease free for a period greater than 63 months in duration. Hence, this study found evidence to support the use of this salvage chemotherapy regime in patients who have previously undergone high dose chemotherapy with tandem transplantation, as well as cisplatin combination chemotherapy.

Cisplatin combination chemotherapy has a definite application in the treatment of metastatic germ cell tumours, demonstrating a 70% cure rate. Numerous treatment strategies have been employed to target the 30% of refractory patients whose tumours progress within 4 weeks of ceasing Cisplatin combination chemotherapy. High dose chemotherapy (HDCT) has been regarded as the most consistent second line treatment option in such patients, providing effective cure and long-term survival. However, subsequent cases of relapse from HDCT have been subjected to a number of differing therapeutic regimes, with little success. Many studies have utilised the chemotherapeutic agents, Paclitaxel and Gemcitabine as single therapies, with response rates of approximately 10-26%. A phase I study performed by the Eastern Cooperative Oncology Group (ECOG) not only demonstrated a similar response rate of 21% with the use of Paclitaxel and Gemcitabine; but also a complete response cure rate of 10.7%. The same dual therapy was employed for the purposes of this study on a sample size of 32 patients who presented with progressive disease following HDCT from an initial population size of 184. The course of therapy comprised six courses of a combined regime of Paclitaxel 100mg/m2 and Gemcitabine 1,000mg/m2 on days 1, 8 and 15 on a monthly interval. Response rates and duration of patient survival were the parameters measured over an 8-year period. The results displayed a response rate of 31%, and observed complete remissions in 18.8% of participants. These patients remained continuously disease-free (NED) on chemotherapy alone for varying lengths of time, ranging from 1 year to over 3 years. One participant demonstrated a much longer NED survival time of greater than 5 years with the application of two separate surgical tumour resections post-therapy. Germ cell tumours demonstrate significant responses and cure rates with chemotherapy in comparison to other solid tumours. The use of a third-line regime of Paclitaxel and Gemcitabine in patients previously exposed to HDCT has been found to prolong long-term disease-free survival and cure in such tumours. Further research into the optimal dosing schedule of this regime is warranted on a larger scale, involving the cooperation of multiple organizations. Reference:Einhorn LH, Brames MJ, Juliar B, et al. Phase II Study of Paclitaxel plus Gemcitabine salvage chemotherapy for Germ Cell tumours after progression following high-dose chemotherapy with tandem transplant. Journal of Clinical Oncology 2007; 25(5); 513-6.