Randomized, double-blind, and multicenter phase II trial of rh-endostatin plus dacarbazine versus dacarbazine alone as first-line therapy for the patients with advanced melanoma.

Abstract

8554 Background: rh-endostatin (Endostar, water-soluble, rES) is an inhibitor of angiogenesis, which is effective as single agent or in combination with chemotherapy for non-small cell lung cancer in phase I/II clinical trials. This study (NCT00813449) was a randomized, double-blind and placebo-controlled phase II trial, aimed to observe the efficacy and safety of rES with dacarbazine (DTIC) as the 1st line therapy for patients (pts) with advanced melanoma. Methods: Untreated pts with ECOG 0/1 and unresectable stage IIIC or IV melanoma (confirmed by histopathology) were enrolled, and randomized (1:1) into Arm A (DTIC 250 mg/m2 d1-5 + placebo d1-14) or Arm B (DTIC 250 mg/m2 d1-5 + rES 7.5 mg/m2 d1-14). Treatment was continued in 21-day cycle until progression or intolerable toxicity occurs. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR) and safety, evaluated every 2 cycles. Results: From Dec. 2008, 120 pts were enrolled and 110 pts evaluable. 30.9% of them were in M1a, 39.1% in M1b, and 29.1% in M1c. Mean treatment cycles were 3.2 (range: 1-10) in Arm A and 4.0 (range: 1-12) in Arm B. Until the last follow-up in Nov. 2011, 27 pts were still alive. The median PFS was 1.5 months (95% CI: 1.35-1.65) in Arm A and 5.0 months in Arm B (95% CI: 2.45-7.55, P=0.004, log-rank test). The median OS was 7.0 months in Arm A (95% CI: 4.41-9.59) versus 16.0 months in Arm B (95% CI: 10.46-21.54, P=0.003, Breslow test). 1-year survival rate was 22.2% versus 51.0%, and 2-year survival rate 8.9% vs.10.2%. No statistical significance was found for both ORR and toxicities. The most common toxicities were increased transaminase (28.9% in Arm A versus 56.1% in Arm B) and leucopenia (14.4% versus 13.4%). The incidence of grade 3-4 toxicity (increased transaminase and thrombocytopenia) was only 1.7% in Arm B. Conclusions: rES plus DTIC may obviously improve mPFS and mOS versus DTIC alone as the 1st line therapy for advanced melanoma. That combining therapy was well tolerated and could be recommended as a new, safe and effective regimen for untreated pts with advanced melanoma.