Legha S S, Ring S, Papadopoulos N, Plager C, Chawla S, Benjamin R
Department of Medical Oncology, M.D. Anderson Cancer Center, Houston, Texas 77030.
Cancer. 1989 Nov 15;64(10):2024-9. doi: 10.1002/1097-0142(19891115)64:10<2024::aid-cncr2820641010>3.0.co;2-v.
Based on the independent activity of cisplatin, vinblastine, and dimethyl-triazeno-imidazole-carboxamide (DTIC) (CVD), a combination of these agents was used in the treatment of patients with advanced melanoma. Vinblastine was used in a dose of 1.6 mg/m2/d for 5 days, DTIC was used in a dose of 800 mg/m2 intravenously (IV) on day 1, and cisplatin was used in a dose of 20 mg/m2/d for 4 days starting on day 2 of chemotherapy. The courses of chemotherapy were repeated at 3-week intervals. All patients were premedicated with antiemetics, and IV hydration was used before cisplatin. Fifty-two consecutive patients were registered and 50 were evaluable for response. Two patients achieved a complete response (CR) and 18 patients had a partial response (PR) for an overall response rate of 40% (95% confidence interval, 27% to 55%). The median duration of response was 9 months and the median survival time of the responders was 12 months. The overall median survival time of patients treated on this protocol was 9 months. The treatment was associated with significant toxicity consisting of nausea, vomiting, diarrhea, and partial hair loss. Additionally, neutropenia with a median nadir granulocyte count of 500/microliters was observed, and significant anemia required blood transfusions in a majority of the patients after three to four courses of chemotherapy. The dose-limiting toxicity was peripheral neuropathy which required discontinuation of cisplatin after six to eight courses of chemotherapy. We believe that this triple-drug regimen has significant activity that appears to be superior to the single-agent activity of these drugs, both in terms of increased response rate and duration of response.
基于顺铂、长春碱和二甲基三氮烯咪唑甲酰胺（DTIC）（CVD）的独立活性，将这些药物联合用于治疗晚期黑色素瘤患者。长春碱的使用剂量为1.6mg/m²/天，连用5天；DTIC在化疗第1天静脉注射（IV），剂量为800mg/m²；顺铂从化疗第2天开始使用，剂量为20mg/m²/天，连用4天。化疗疗程每3周重复一次。所有患者均预先使用止吐药，在使用顺铂前进行静脉补液。连续登记了52例患者，其中50例可评估疗效。2例患者达到完全缓解（CR），18例患者部分缓解（PR），总缓解率为40%（95%置信区间，27%至55%）。缓解的中位持续时间为9个月，缓解患者的中位生存时间为12个月。按照该方案治疗的患者总体中位生存时间为9个月。该治疗伴有显著毒性，包括恶心、呕吐、腹泻和部分脱发。此外，观察到中性粒细胞减少，中位最低点粒细胞计数为500/微升，在三到四个化疗疗程后，大多数患者出现严重贫血需要输血。剂量限制性毒性是周围神经病变，在六到八个化疗疗程后需要停用顺铂。我们认为，这种三联药物方案具有显著活性，无论是在缓解率还是缓解持续时间方面，似乎都优于这些药物的单药活性。
