奈达铂治疗恶性肿瘤的临床研究

目的 观察奈达铂（NDP）单药治疗头颈部鳞癌、非小细胞肺癌、食管癌、卵巢上皮癌的临床疗效及安全性;比较NDP与顺铂（DDP）联合化疗治疗上述肿瘤的疗效和安全性。方法 NDP单药组：NDP100mg,／m^2,第1天,每3周为1个周期,至少2个周期。联合化疗组：NDP80mg,／m^2,第1天,或DDP30mg,／m^2,第1～3天,分别联合5-氟尿嘧啶（5-Fu）、长春瑞滨（NVB）、长春花碱酰胺（VDS）＋5-Fu、紫杉醇（PTX）或环磷酰胺（CTX）,每3周为1个周期,至少2个周期。结果 NDP单药组37例,NDP联合化疗组139例,DDP联合化疗对照组61例。NDP单药对晚期非小细胞肺癌的有效率为10．5％（2／19）。1例卵巢癌和1例头颈部鳞癌取得PR。对既往铂类药物治疗失败的非小细胞肺癌和卵巢癌患者,NDP单药仍有一定疗效。NDP联合化疗对非小细胞肺癌、卵巢癌、头颈鳞癌和食管癌的有效率分别为33．9％（21／62）、44．8％（13／29）、20．0％（3／15）和18．2％（4／22）,与DDP联合化疗对照组的结果相似。对初治的非小细胞肺癌患者,NDP联合化疗组的有效率（35．7％）优于DDP联合化疗对照组（17．1％,P=0．045）。单药NDP的不良反应主要为骨髓抑制（白细胞和血小板减少、贫血）、恶心和呕吐。NDP联合化疗组患者骨髓抑制、肾功能损害与DDP联合化疗对照组相似,呕吐反应明显轻于DDP联合化疗对照组,但肝功能损害比DDP联合化疗对照组明显。结论 NDP单药对头颈鳞癌、非小细胞肺癌和卵巢癌有一定疗效。NDP联合化疗对头颈鳞癌、非小细胞肺癌、卵巢癌和食管癌疗效肯定,胃肠反应较DDP联合化疗轻,治疗中应注意监测肝功能。

Phase II multicenter clinical trial of nedaplatin in the treatment of malignant tumors

OBJECTIVE: To evaluate and compare the efficacy and safety of Nedaplatin (NDP)-based regimen and cisplatin (DDP)-based regimen for head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), esophageal cancer and ovary epithelial cell carcinoma. METHODS: Single agent group: NDP was administered at a dose of 100 mg/m(2) on D1, every 3 weeks for at least 2 cycles. Combination chemotherapy group: combined with 5-Fu, NVB, VDS + 5-Fu, PTX or CTX respectively, NDP 80 mg/m(2) on D1 or DDP 30 mg/m(2) on D1-3, every 3 weeks for at least 2 cycles was given. RESULTS: Of 237 patients in this trial, 37 were treated by single Nedaplatin, 139 by NDP-based regimen, 61 by DDP-based regimen in the control group. The response rate of single Nedaplatin chemotherapy for advanced NSCLC was 10.5% (2/19), for ovary carcinoma (1/3) and HNSCC (1/1). For NSCLC and ovary carcinoma patients who had failed in the previous DDP-based chemotherapy, the response rates by single NDP chemotherapy were still 9.1% and 33.3%. The response rate of NDP-based combination regimen for NSCLC, ovary carcinoma, HNSCC and esophageal cancer was 33.9% (21/62), 44.8% (13/29), 20.0% (3/15) and 18.2% (4/22), respectively, which was not statistically different from the rate of controlled group treated by DDP-based regimen. For chemonaive NSCLC, the effect of NDP-based combination regimen (35.7%) was significantly superior to the effect of DDP-based regimen (17.1%) (P = 0.045). The most common adverse events of nedaplatin were myelosuppression (leukopenia, thrombocytopenia, anemia), nausea and vomiting. The myelosuppression and renal toxicity of NDP-based regimen were similar to that of DDP-based regimen, but vomiting was milder than that of DDP-based regimen (54% vs. 75.4%), and grade I/II liver toxicity was more common in the NDP-based regimen than in DDP-based regimen (10.8% vs. 0). CONCLUSION: Nedaplatin is effective in the treatment for HNSCC, NSCLC and ovary carcinoma. Compared with the control group treated by DDP-based regimen, nedaplatin-based combination chemotherapy has similar effect on HNSCC, NSCLC, ovary carcinoma and esophageal cancer. Gastrointestinal reaction of nedaplatin is milder than that of cisplatin but the liver function during chemotherapy must be monitored closely.