A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial

Abstract

This phase II trial describes the use of TIP chemotherapy (paclitaxel, ifosfamide and cisplatin) as salvage for patients with metastatic germ cell cancer (GCC) who have failed initial BEP (bleomycin, etoposide and cisplatin) chemotherapy. Patients with first relapse following BEP for metastatic GCC, confirmed by biopsy or sequentially rising markers, received four courses of TIP (paclitaxel 175 mg m À2 day 1, followed on days 1 -5 by ifosfamide 1 g m À2 intravenously (i.v.) and cisplatin 20 mg 2 i.v.) at 3-weekly intervals. The primary outcome measure was response to TIP. In all, 51 patients were registered, of whom 43 were eligible for response assessment. Eight achieved complete remission (CR) and 18 a partial remission with negative markers (PR Àve ); favourable response rate (FRR ¼ CR þ PR Àve ) 60%, 95% CI (44 -75%); survival at 1 year was 70% (56 -84%) and failure-free survival 36% (22 -50%). In the group of 26 patients meeting the 'good-risk' criteria described by the Memorial Hospital, the FRR was 73% (52 -88%) compared with 41% (18 -67%) for the 17 'poor-risk' patients. These results are inferior to those previously reported for TIP in a single-centre study when it was given more intensively, at higher dose and with growth factor support. Nonetheless, TIP as described here can cure a substantial proportion of patients.

Irinotecan and nedaplatin as salvage therapy for patients with advanced germ cell tumors following intensive treatment with cisplatin-based combination chemotherapies

“…Motzer et al [16] reported their findings in 46 patients with recurrent GCTs treated with TIP, achieving a very high CR rate of 77 %. Mead et al [17] subsequently reported similar but somewhat inferior results with less-intensive TIP in a second-line salvage setting, showing a response rate of 38 %. Despite being encouraging response rates in a salvage setting, TIP failed to lead to a marked improvement in long-term disease remission compared with conventional salvage chemotherapies.…”

“…1 Overall survival in 20 patients with advanced germ cell tumors who were judged to be refractory or relapsed after BEP (bleomycin, etoposide, and cisplatin) and TIP (cisplatin, ifosfamide and paclitaxel) therapies, and subsequently received irinotecan and nedaplatin powerful activity against such intractable GCTs [16,17]. Motzer et al [16] reported their findings in 46 patients with recurrent GCTs treated with TIP, achieving a very high CR rate of 77 %.…”

Testicular germ cell tumours

“…27 The chance of cure depends on the extent of disease at relapse and initial sensitivity of the disease. A recent multivariate analysis identified five prognostic groups with a chance of cure, varying from less than 10% to over 70%.…”

Consolidative high-dose chemotherapy after conventional-dose chemotherapy as first salvage treatment for male patients with metastatic germ cell tumours

“…Impressive results have been reported using either conventional-dose chemotherapy (CDCT) or high-dose chemotherapy with stem cell rescue (HDCT). [1][2][3][4] However, these reports from single institutions are confounded by patient selection. A single randomized trial comparing CDCT to a HDCT strategy has been completed and reported as negative, but has also been subject to criticism and refuted to some degree by a large single institutional report influential in suggesting benefit of HDCT at first salvage.…”