Temozolomide in combination with interferon α‐2b in patients with metastatic melanoma

摘要: BACKGROUND Metastatic melanoma (MM) is associated with a high risk of central nervous system (CNS) metastases, and current chemotherapy does not adequately treat or protect patients MM against CNS metastases. Therefore, the authors initiated Phase I study to determine pharmacokinetics safety profile temozolomide (TMZ), novel oral alkylating agent known cross blood-brain barrier, in combination interferon α-2b (IFN-α2b). METHODS Twenty-three were enrolled this single-center, open-label study. Patients metastasis excluded. One cohort (n = 6 patients) received TMZ (200 mg/m2 per day) for 5 days every 28-day cycle plus subcutaneous IFN-α2b (5 million International Units [MIU]/m2 day, 3 times week). A second 17 150 day on same schedule escalating doses (5.0 MIU/m2 7.5 10 week). RESULTS The most common adverse events fatigue, fever, nausea/emesis, anxiety, diarrhea. Most toxicity was mild moderate severity. The primary dose-limiting thrombocytopenia. maximum tolerated dose either 200 5.0 MIU/m2. Four (17%) had objective responses (one complete response three partial responses), four stable disease. median survival 9 months. affected by coadministration IFN-α2b. CONCLUSIONS TMZ can be combined safely IFN-α2b. This regimen demonstrated clinical activity merits further investigation define its effect incidence brain Cancer 2003;97:121–7. © 2003 American Society. DOI 10.1002/cncr.11041