Abstract

7548 Background: Treatment of metastatic melanoma (MM) remains disappointing since an objective response is usually obtained in only 12 to 20% of patients. A combined approach by chemo-immunotherapy might increase the rates of response through a synergistic anti-tumoral action. Accordingly, a phase I/II clinical trial using an association of Temozolomide(TMZ) with Peg-interferon α2b (PEG) in patients with MM was designed. The first aim of this study was to determine the maximal tolerated dosage (MTD) of both drugs. A secondary objective was to evaluate the antitumoral response rate. Methods: Patients with MM in first or second line of treatment and without cerebral metastasis were enrolled in a multicenter, prospective, open-label study. Dose escalation was performed according to the MCRM scale and resulted in four different dose levels (DL) of patients. DL1 : TMZ 150mg/m2 5 d/w each 4 weeks and Peg 0.5 μg/w, DL2 : TMZ 150 mg/ m2 5d/w and Peg 1.0 μg/w, DL3 : TMZ 200 mg/ m2 5 d/w and Peg 0.5 μg/w, DL4 : TMZ 200 mg/ m2 5d/w and Peg 1.0 μg/w. Patients received a maximum of 6 cycles. Results: 31 patients were enrolled in the study. One patient was enrolled in the DL1, 1 in the DL2, 18 in the DL3 and 11 in the DL4. In the DL4 group, 4/11 patients experienced a hematologic dose-limiting toxicity(DLT) (grade IV thrombopenia) and 4 patients had non dose-limiting toxicity. These 8 patients were thereafter treated according to the DL3. An objective clinical and morphological response was observed in 4 patients (2 complete responses and 2 partial responses). Four stable diseases were observed and 8 patients were alive 9 to 19 months after enrollment (median survival: 364 days; CI 95% = 201–358). All responses were observed in the DL3–4 patients groups. Conclusion: The combination of TMZ with PEG in MM showed an hematological DLT. The maximal tolerated dose was obtained in DL3 group. The combined treatment at DL3 was effective (13% of objective response and 10% of stabilization) and deserves further investigations to define its place in the treatment of patients with MM. No significant financial relationships to disclose.

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