A phase II study of fotemustine plus dacarbazine with dendritic cell vaccines as first-line therapy for Chinese patients with advanced acral lentiginous melanoma

作者：Si Lu; Chi Zhi hong; Yuan Xiang qing; Cui Chuan liang; Sheng Xi nan; Guo Jun^*

来源：Chinese Journal of Cancer Research, 2009, 21(1): 13-19.

DOI：10.1007/s11670-009-0013-z

• Fotemustine
• Dacarbazine
• Dendritic cell
• Melanoma

To investigate fotemustine plus dacarbazine (DTIC) with dendritic cell (DC) vaccines on patients with advanced acral lentiginous melanoma (ALM). Fotemustine is a cytotoxic alkylating agent with a remarkable antitumor activity as single agent but also in association with (DTIC). DC is the strongest antigen presenting cell which could induce durable clinical responses.
This was a single-center study. Between July 2003 and June 2006, twenty-eight chemotherapy-naive patients of advanced ALM received fotemustine 100 mg/m(2), d(1, 12), DTIC 400 mg/d d(2-6), DC vaccines subcutaneously d(7, 9, 13) repeated every 28 days. Ten HLA-A02+24+ patients received vaccines pulsed with melanoma antigen derived peptides, melanoma antigen recognized by T-cells 1 (Mart-1) and S-100. Eighteen patients received DC loaded with allogeneic melanoma lysate. The primary end-point was progression free survival (PFS). Secondary end-points were overall survival (OS), overall response rate (ORR) and toxicity. Tumor assessment was performed every 8 weeks and evaluated according to response evaluation criteria in solid tumors (RECIST).
The 15 men and 13 women had a median age of 51 years. 16 patients had stage M1c disease and 11/16 had liver metastasis. Patients received an average of 3.82 +/- 1.25 cycles. Follow-up for the 18 surviving patients ranged from 7-41 months with a median of 12 months. Median PFS was 8.5 months (95% CI: 7.86-15.21) with 12 patients remaining progression free. Only 10 patients died. Median OS was 12 months (95% CI: 10.33-18.24). ORR (CR+PR) was 35.7% including 3 complete response (CR) and 7 partial response (PR). Six patients had disease stable. A total of 19 Grade III/IV toxicities were observed including thrombocytopenia (n=8), neutropenia (n=5), fatigue (n=6) and hypersensitivity reaction (n=1). One patient died of Grade IV thrombocytopenia.
Fotemustine and dacarbazine plus DC vaccines are safe and tolerable to Chinese ALM patients. The regimen brings clinical benefit with a higher ORR and may provide a survival advantage. Updated survival data will be presented.

• 出版日期2009-3
• 单位北京大学; 北京市肿瘤防治研究所