Background: Temozolomide (TMZ) is an oral alkylating agent; it produces DNA methyl adducts which are removed by the DNA repair enzyme AGAT. In vitro studies suggest that CDDP may enhance the antitumor activity of TMZ due to the ability of CDDP to down-regulate AGAT activity. In a previous phase I study, combination of TMZ and CDDP was tested, and the recommended dose for each drug was defined. On the basis of these results, we designed a phase II study to evaluate the activity and safety profile of the TMZ-CDDP association in patients with advanced melanoma. Patients and methods: From March 2001 to March 2002, 37 patients with metastatic melanoma, not amenable to surgery were enrolled in this study. All eligible patients were treated with combination of cisplatin (CDDP) 75 mg/m2 i.v. d 1, and temozolomide (TMZ) 200 mg/m2 p.o. days 1-5 recycled every 4 weeks. Interferon ?2b (IFN ?2b) was administered at end of chemotherapy to responsive patients at the dose of 5 MIU s.c. 3 times a week for one year. Results: A total of 174 courses were administered, with a median number of 4 courses/patient (range 1-10). After chemotherapy, 9 CRs and 9 PRs were observed for an overall response rate of 48.6% (95% C.I., 31.9%-65.6%). One of 5 patients with initial brain metastases obtained a complete response to the therapy. Five of nine CR patients were still with no evidence of recurrence, ranging from 82+ to 28+ weeks. Median survival time was 40 weeks. The schedule was well tolerated, with the most frequent adverse events reported being nausea and vomiting (59%), alopecia (14%), fatigue (11%), all well controlled by supportive therapy. Haemotologic toxicities were mild to moderate. Side effects attributable to IFN ?2b were also mild and manageable. Conclusions: The combination of TMZ and CDDP seems to be active in untreated patients with advanced melanoma. Absence of recurrence in majority (5/9; 56%) of CRs patients seems to indicate that IFN may act on the duration of the response to chemotherapy. The schedule was well tolerated with nausea and vomiting as the most frequent adverse events.
Temozolomide and cisplatin in avdanced malignant melanoma
Palmieri Giuseppe;
2005
Abstract
Background: Temozolomide (TMZ) is an oral alkylating agent; it produces DNA methyl adducts which are removed by the DNA repair enzyme AGAT. In vitro studies suggest that CDDP may enhance the antitumor activity of TMZ due to the ability of CDDP to down-regulate AGAT activity. In a previous phase I study, combination of TMZ and CDDP was tested, and the recommended dose for each drug was defined. On the basis of these results, we designed a phase II study to evaluate the activity and safety profile of the TMZ-CDDP association in patients with advanced melanoma. Patients and methods: From March 2001 to March 2002, 37 patients with metastatic melanoma, not amenable to surgery were enrolled in this study. All eligible patients were treated with combination of cisplatin (CDDP) 75 mg/m2 i.v. d 1, and temozolomide (TMZ) 200 mg/m2 p.o. days 1-5 recycled every 4 weeks. Interferon ?2b (IFN ?2b) was administered at end of chemotherapy to responsive patients at the dose of 5 MIU s.c. 3 times a week for one year. Results: A total of 174 courses were administered, with a median number of 4 courses/patient (range 1-10). After chemotherapy, 9 CRs and 9 PRs were observed for an overall response rate of 48.6% (95% C.I., 31.9%-65.6%). One of 5 patients with initial brain metastases obtained a complete response to the therapy. Five of nine CR patients were still with no evidence of recurrence, ranging from 82+ to 28+ weeks. Median survival time was 40 weeks. The schedule was well tolerated, with the most frequent adverse events reported being nausea and vomiting (59%), alopecia (14%), fatigue (11%), all well controlled by supportive therapy. Haemotologic toxicities were mild to moderate. Side effects attributable to IFN ?2b were also mild and manageable. Conclusions: The combination of TMZ and CDDP seems to be active in untreated patients with advanced melanoma. Absence of recurrence in majority (5/9; 56%) of CRs patients seems to indicate that IFN may act on the duration of the response to chemotherapy. The schedule was well tolerated with nausea and vomiting as the most frequent adverse events.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
