【文章名】Phase I/II study of sequential dose-intensified ifosfamide, cisplatin, and etoposide plus paclitaxel as induction chemotherapy for poor prognosis germ cell tumors by the German testicular cancer study group
Phase I/II study of sequential dose-intensified ifosfamide, cisplatin, and etoposide plus paclitaxel as induction chemotherapy for poor prognosis germ cell tumors by the German testicular cancer study group
[摘要]：PurposeTo evaluate the feasibility and the toxicity of sequential, dose-intensified chemotherapy combined with paclitaxel plus peripheral blood-derived hematopoietic stem-cell support (PBSC) for patients with untreated metastatic germ cell tumors (GCTs) who have poor International Germ Cell Consensus Cancer Group prognostic features.Patients and MethodsPaclitaxel was added to high-dose (HD) etoposide, ifosfamide, and cisplatin (VIP; etoposide 1,500 mg/m(2), ifosfamide 10,000 mg/m(2), and cisplatin 100 mg/m(2); cumulative dose; days -6 through -2 per cycle) at three dose levels (135, 175, and 225 mg/m(2)) applied on day -6. Cycles were supported by PBSC and granulocyte colony-stimulating factor. One cycle of standard VIP was administered before start of HD-VIP plus paclitaxel cycles to collect autologous PBSC.ResultsFifty-two of 53 patients receiving 152 cycles were assessable. As expected, myelosuppression was the major adverse effect. Median durations of leukocytes less than 1,000/mu L and thrombocytes less than 25,000/mu L were 6 and 4 days, respectively, independently of the dose of paclitaxel applied. WHO grade 2 neurotoxicity and grade 3 encephalopathy were observed in 5% of patients each. Other main adverse effects observed were stomatitis, diarrhea, and obstipation. Seventy-nine percent of patients achieved a favorable response to chemotherapy plus secondary surgery. After a median follow-up time of 41 months in surviving patients, the calculated 2- and 5-year survival rates were 77.6% (95% CI, 65.4% to 89.9%) and 75.2% (95% CI, 62.5% to 87.8%), respectively.ConclusionDose-intensive, sequential HD-VIP plus paclitaxel up to a dose of 225 mg/m(2) in patients with poor prognosis GCT is a feasible approach. The regimen warrants investigation for its therapeutic potential in an expanded cohort of poor prognosis GCT patients.
