GOG 169:CISPLATIN VS CISPLATIN + PACLITAXEL IN SQUAMOUS CELL CARCINOM

对于晚期、持续性或复发性宫颈鳞状细胞癌患者，不再适合手术切除或放射治疗，预后很差。 在这种临床环境中，有效化疗的需求是有组织的，最佳治疗方法尚未确定。 多年来，顺铂一直被认为是治疗宫颈癌最有效的药物，初始反应率高达50%。 GOG在三种剂量方案下进行了一项顺铂研究，以观察是否可以通过增加剂量强度来改善结果。 虽然随着剂量从50 mg/m2增加到100 mg/m2，每3周一次，缓解率从21%增加到31%，但完全缓解率、无进展间期或生存率没有相关改善。 单药顺铂化疗对总生存率的影响是有争议的。 紫杉醇是一种从太平洋紫杉树皮中提取的二萜类化合物，其细胞毒性被认为是通过稳定微管蛋白聚合物束，从而干扰微管组装和细胞复制来发挥作用的。 它已被证明对许多实体瘤具有广泛的活性，包括卵巢癌、乳腺癌和子宫内膜癌。 GOG报告Paclitaxel治疗晚期宫颈鳞状细胞癌的有效率为17%。 顺铂和紫杉醇的组合已被有效地用于对抗许多恶性肿瘤，目前正在对包括宫颈癌在内的各种鳞状细胞癌进行研究。 本研究将确定与顺铂单药治疗相比，顺铂+紫杉醇联合治疗是否能改善晚期宫颈鳞癌的缓解率、无进展间期和/或生存率。 此外，在标准治疗本质上可能被视为姑息治疗的临床环境中，本研究将评估两组在毒性和/或生活质量方面的差异。

For patients with advanced, persistent or recurrent squamous cell carcinoma of the cervix no longer amenable to surgical resection or radiation therapy, the prognosis is bleak. The need for effective chemotherapy in this clinical setting is well-organized, and optimal treatment has yet to be defined. For a number of years, cisplatin has been considered the most active drug against cervical cancer with initial response rates as high as 50%. The GOG conducted a study of cisplatin at three dose schedules to see if improved results could be achieved through increased dose intensity. Although the response rate increased from 21% to 31% with an increase in dose from 50 mg/m2 to 100 mg/m2 every three weeks, there was no associated improvement in the complete response rate, progression-free interval, or survival. The impact of single-agent cisplatin chemotherapy on overall survival is debatable. Paclitaxel is a diterpenoid compound extracted from the bark of the Pacific yew and its cytotoxicity is believed to be exerted via stabilization of tubulin polymer bundles, thus interfering with microtubular assembly and cell replication. It has demonstrated broad activity against a number of solid tumors, including cancers of the ovary, breast and endometrium. The GOG reported a 17% response rate for Paclitaxel against advanced squamous cell carcinoma of the cervix. The combination of cisplatin and Paclitaxel has been effectively used against a number of malignancies and is presently undergoing investigation against various squamous cell cancers, including cervical cancer. The present study will determine if the combination of cisplatin plus Paclitaxel improves the response rate, progression-free interval, and/or survival in advanced squamous cervical cancer compared to treatment with cisplatin alone. Furthermore, in a clinical setting where standard treatment may be viewed as palliative in nature, the study will assess differences in the two arms with respect to toxicity and/or quality of life.