CL Cui, L Si, ZH Chi, XN Sheng, LL Mao, XWang, BX Tang, B Lian, XQ Yan, J Guo

Department of Renal cancer and Melanoma, Beijing Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing.

Objective: Aphase II study has revealed that rh-Endostatin (Endostar) was more effective when combining with dacarbazine (DTIC) for metastatic melanoma patients (pts)with good tolerance especially for acral primary. Preclinical data suggest that continuous infusion of endostatin is more potent than intermittent dosing. This was a phase II study to observe the efficacy and safety of continuous intravenous infusion (CIV) of Endostar with DTIC as 1st line therapy for ptswith metastatic acral melanoma. Method: Twenty pts with treatment naive, C-Kit/BRAFwild type, metastatic acral melanoma wereenrolled; the efficacy and safety of DTIC 250 mg/m² d1-5 andEndostar CIV (Baxter infusion pump 2ml/h, 7.5mg/m²/dor 15mg/m²/d d1-14, with10 pts respectively ) were evaluated. It was continued in a 28-day cycle until disease progression (PD) or toxicity intolerable. Primary endpoint was progression free survival (PFS),Secondary endpoints included disease control rate (DCR) and safety. Result: From Dec 2013 to Oct 2014,13pxs were enrolled in Endostar 7.5mg/m²/d group (group A), after that another 10 pts in 15mg/m²/d group (group B). In group AM1a disease was 30%, M1b50% and M1c 20%; In group B M1a 20%, M1b30% and M1c 50%. Mean treatment cycle was 3.1 (1-6) in group A and 2.6 (1-6) in group B. Until last follow-up of Jan. 2015, 12pxs got PD. The estimated mPFS was 3.0 mo (95%CI 0.86~5.14 mo) in group A and6.0 mo in group B (95%CI 1.69~10.31 mo, P=0.178,log-ranktest). It has a higher DCR in group B (80%,8SD, 2PD) than in group A (50%, 5SD, 5PD) without statistical significance. This combination was well tolerated without grade 3-4 toxicity, the most common side effect was intermittent palpitation in group B (2/10) which ECG monitoring showed sinus tachycardia without ST-T change. Conclusion: Endostarwas safely administered by continuous infusion, and 15mg/m²/d combined with DTIC might get better estimated PFS and DCR than 7.5mg/m²/d for metastatic acral melanoma. But it still needs a controlled study with a larger sample size and longer follow up time to betested.

Key Words: melanoma