BERKELEY, CA (UroToday.com) - Long-term survival after treatment with gemcitabine and oxaliplatin +/- paclitaxel, plus secondary surgery in patients with cisplatin-refractory and/or multiple relapsed germ-cell tumors - After a prolonged observation period of almost 2 years, we present the survival data of 2 previously published, phase II studies on combination chemotherapy with gemcitabine, oxaliplatin +/- paclitaxel, in patients with germ-cell tumors and multiple relapses after cisplatin-based chemotherapy or high-dose chemotherapy.
The first study had investigated the double combination of gemcitabine and oxaliplatin (GO) in 35 patients and was published after a median follow-up of 6 months (range 0.5 to 18+ months).[1] In the second study, the triple combination of gemcitabine, oxaliplatin, and paclitaxel (GOP) was evaluated in 41 patients and was presented with a median follow-up of 5 months (range 0 to 20+).[2] At the time of previous publication, a total of 29 out of 76 patients were still alive: 9 patients (12%) were free of disease after chemotherapy, +/- surgery (GO 3/35 and GOP 6/41), and 4 patients had achieved a marker negative partial remission, but they had not yet undergone secondary surgery within the short follow-up time (GO 1/35 and GOP 3/41).
The present survival data were assessed after a median follow-up time of 19 months (range 2 – 86) for the 29 patients still alive at the time of the previous publications. Median overall survival for all 76 patients of both studies was 8 months (range 1 to 84 months) and 17 months (range 6 to 84 months) for the 37 patients (49%) showing any response to GO or GOP treatment.
In total, 8 of the 76 patients (11%) remain disease free at their current evaluation, with a median overall survival time of 33+ months (range 28+ to 59+). One of them was treated in the GO trial (1/35; 3%), and 7 patients were treated within the GOP trial (7/41; 17%). Two of these 8 patients, one with GO and GOP treatment each, had been absolutely refractory to previous, cisplatin-based chemotherapy. One of them had been pretreated with paclitaxel-based chemotherapy prior to responsing to GOP therapy.
Remarkably, only one of these 8 patients had achieved a complete remission after chemotherapy with GOP alone. The other 7 patients had achieved a marker negative partial remission, one after GO and 6 after GOP treatment, and 6 of them were rendered disease free after aggressive secondary surgery, achieving complete resection. Persistent vital carcinoma cells were found in 4 of these 6 patients (67%). The other patient with PR- who did not undergo secondary surgery relapsed 2 months later but achieved a complete remission with further salvage chemotherapy, plus additional secondary surgery.
These results demonstrate that completeness of resection of all residual lesions after combination chemotherapy is the cornerstone of long-term survival, even in these multiple, pretreated patients, and should, therefore, be aspired whenever possible.
Obviously, a direct retrospective comparison of the GO and GOP combination chemotherapy regimen must be interpreted with caution, as the data comes from independently performed phase II trials. However, comparing the outcome data of these 2 studies, long-term survival seems to be achieved more often after chemotherapy, plus secondary surgery in patients treated with triple combination chemotherapy with GOP (17%) than in patients treated with the double combination chemotherapy with GO (3%). Therefore, we suggest the use of a triple combination regimen in all patients deemed fit enough for this approach, preferably in cases with a limited number of metastases for whom secondary resectability seems to be achievable after response to chemotherapy.
References:
- Kollmannsberger C, Beyer J, Liersch R, Schoeffski P, Metzner B, Hartmann JT, et al. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol. 2004;22(1):108-114.
- Bokemeyer C, Oechsle K, Honecker F, Mayer F, et al. Combination chemotherapy with gemcitabine, oxaliplatin, and paclitaxel in patients with cisplatin-refractory or multiply relapsed germ-cell tumors: a study of the German Testicular Cancer Study Group. Ann Oncol. 2008;19(3):448-453.
Written by:
Karin Oechsle,a Christian Kollmannsberger,b Friedemann Honecker,a Frank Mayer,c Cornelius F Waller,d Jörg T Hartmann,e Ina Boehlke,1 Carsten Bokemeyer,a and the German Testicular Cancer Study Group (GTCSG) as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
- Dept. of Oncology/Hematology/Bone Marrow Transplantation/Pneumology, University Medical Center Eppendorf, Hamburg, Germany
- Division of Medical Oncology, British Columbia Cancer Agency-Vancouver Cancer Center, Vancouver Canada
- Dept. of Oncology/Hematology/Immunology/ Rheumatology/Pulmology, University of Tuebingen Medical Center, Tuebingen, Germany
- Dept. of Hematology/Oncology, University of Freiburg, Germany
- Dept. Of Hematology and Internal Oncology, University of Schleswig-Holstein, Campus Kiel, Germany
