First salvage treatment in patients with advanced germ cell cancer after cisplatin-based chemotherapy: analysis of a registry of the German Testicular Cancer Study Group (GTCSG).

PURPOSE: We analyzed prognostic categories at first relapse according to the International Prognostic Factors Study Group (IPFSG) criteria as well as the efficacy of salvage treatment. METHODS: 143 patients with relapsed or refractory germ cell cancer undergoing first salvage treatment with conventional-dose (CD-CX, n = 48) or high-dose chemotherapy with autologous stem cell support (HD-CX, n = 95) contributed by nine centers were retrospectively analyzed. RESULTS: Prognostic subgroups according to IPFSG criteria were: very low risk 13/143, low risk 36/143, intermediate risk 66/143, high risk 22/143, and very high risk 6/143 patients. The IPFSG categories significantly correlated with overall survival (OS) (p = 0.025) after 1st salvage treatment. After a median follow-up of 19 months, 55 % of all patients had relapsed and 33 % had died. For the entire cohort, progression-free survival (PFS) rate after 2 years was 43 %, and OS rate after 5 years was 52 %. Compared to the HD-CX group, vital carcinoma was found more often in secondarily resected lesions following CD-CX (22/29 vs. 22/45; p = 0.021). Second relapse rate was higher with 75 versus 44 %, resulting in a shorter median PFS with 8 versus 42 months (p < 0.001), but this did not translate into different OS (p = 0.931). At subsequent relapses, 26/36 patients received HD-CX as ≥2nd-salvage treatment. CONCLUSION: This analysis confirms the prognostic value of the IPFSG prognostic score. HD-CX seemed superior to CD-CX as first salvage treatment with respect to PFS in this retrospective analysis.

Long-term survival after treatment with gemcitabine and oxaliplatin with and without paclitaxel plus secondary surgery in patients with cisplatin-refractory and/or multiply relapsed germ cell tumors.

BACKGROUND: Chemotherapy including gemcitabine, oxaliplatin, and/or paclitaxel has shown efficacy in germ cell tumor patients after progression during cisplatin-based chemotherapy or relapse after high-dose chemotherapy including complete responses in 5-15%. OBJECTIVE: Most studies have been published with a short follow-up. We present the long-term outcome of two previously reported trials. DESIGN, SETTING, AND PARTICIPANTS: Two phase 2 trials have evaluated chemotherapy with gemcitabine plus oxaliplatin alone (GO) or plus paclitaxel (GOP) including a total of 76 patients (35 GO and 41 GOP). At first publication, 29 patients were still alive and 9 patients (12%) were free of disease after chemotherapy with or without surgery: GO, 3 of 35 (9%) and GOP, 6 of 41 (15%). MEASUREMENTS: Survival and follow-up time were calculated using the Kaplan-Meier method from the beginning of study treatment until the date of death or the date of the last follow-up. RESULTS AND LIMITATIONS: After a median follow-up of 19 mo (2-86 mo) for the 29 patients still alive, 11% of all patients (8 of 76) were free of disease for >2 yr: 1 of 35 patients (3%) after GO and 7 of 41 patients (17%) after GOP. Three patients with complete remission (CR), two after GO and one after GOP, relapsed. Two others treated with GOP were rendered disease free: One patient with partial remission and short follow-up underwent secondary surgery, and another patient, who had relapsed 2 mo after GOP, achieved a CR after salvage treatment. Overall survival time is ≥33 mo (range: ≥ 28-59 mo) in these eight patients. CONCLUSIONS: Long-term survival can be achieved in about 10-15% of patients with cisplatin-refractory or multiply relapsed germ cell tumor with GO(P) chemotherapy. Aggressive secondary surgery following partial remission is a crucial part of this salvage treatment.

Patterns of relapse after chemotherapy in patients with high-risk non-seminomatous germ cell tumor.

OBJECTIVES: We investigated the pattern of relapse after chemotherapy in patients with high-risk germ cell tumor (GCT) to critically review common follow-up procedures including close monitoring of serum tumor markers and radiologic procedures. METHODS: 645 patients received first-line (434 patients) or salvage platinum-based (211 patients) high-dose chemotherapy in three multicenter trials. Retrospective analysis comprised 77 patients after first-line and 61 after salvage chemotherapy, who had achieved at least a partial remission but progressed afterwards. RESULTS: At relapse, 24% of the patients presented with an isolated elevation in serum tumor markers, 26% with pathologic radiologic confirmation with negative tumor markers, and 42% with elevated tumor markers and radiologically confirmed progression. Relapse was detected by clinical symptoms in 8%. 46% relapsed within 3 months and 97% within 2 years. Relapse pattern did not correlate with tumor marker status or metastasis location prior to chemotherapy, line of chemotherapy, response status after chemotherapy or time point of relapse. CONCLUSION: In high-risk GCT patients, relapse after chemotherapy is detected either by tumor marker elevation alone, radiologic imaging alone or both, in one third each. Close monitoring including serum tumor markers, radiologic imaging and clinical examination appears warranted within the first 2 years.

Four consecutive multicenter phase II trials of adjuvant chemoradiation in patients with completely resected high-risk gastric cancer: the experience of the German AIO/ARO/CAO group.

PURPOSE: Feasibility and efficacy of four different adjuvant radiochemotherapy regimens in patients with completely resected gastric cancer were evaluated in consecutive cooperative phase II trials using different 5-fluorouracil (5-FU)-based combination chemotherapies (CTX) and 5-FU-enhanced radiotherapy. METHODS: Between 2000 and 2005, 157 patients with completely resected gastric adenocarcinoma were included. The study design was based on two cycles of CTX and irradiation with 45 Gy plus concomitant 5-FU 225 mg/m(2) per 24 h between these two cycles. CTX cycles consisted of 5-FU, folinic acid (FA), cisplatin plus paclitaxel (FLPP); 5-FU, FA and cisplatin (FLP); 5-FU, FA and irinotecan (FLI); or 5-FU, cisplatin plus docetaxel (FPD). RESULTS: Median follow-up for all four trials was 18 months (range, 1-64) without significant difference between the four regimens: FLPP 30 months (2-46+), FLP 18 months (1-64+), FLI 15 months (1-26), FPD 10 months (5-19+). Treatment associated toxicity was tolerable and did not differ significantly between the four CTX regimens. Across all patients grade (3/4), toxicities during the first cycle/chemoradiation/second cycle consisted of leukocytopenia 4%/2%/30%, anorexia 5%/10%/6%, diarrhea 6%/1%/3%, nausea 2%/7%/2%. Early death occurred in one patient due to Pneumocystis carinii pneumonia. Median progression free survival was 23 months for FLPP, 18 months for FLP, 14 months for FLI, 9 months for FPD (not significant). One-year-overall survival rates were 95% for FLPP, 82% for FLP, 94% for FLI, 86% for FPD. CONCLUSION: Adjuvant radiochemotherapy in patients with gastric cancer can be safely given continuous infusion of 5-FU at 225 mg/m(2) per day. In addition, a variety of 5-FU-based multiagent chemotherapy regimen with defined activity in gastric cancer appears both safe and effective when given prior and after radiochemotherapy in this setting.