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

对于晚期、持续性或复发的宫颈鳞状细胞癌患者，不再接受手术切除或放射治疗，预后黯淡。在这种临床环境下，对有效化疗的需求是有组织的，最佳治疗尚未确定。多年来，顺铂一直被认为是治疗宫颈癌最有效的药物，初步有效率高达50%。GOG在三种剂量方案下对顺铂进行了一项研究，以确定是否可以通过增加剂量强度来改善结果。尽管每三周剂量从50 mg/m2增加到100 mg/m2，有效率从21%增加到31%，但在完全应答率、无进展间期或生存期方面没有相关的改善。单药顺铂化疗对总存活率的影响尚有争议。紫杉醇是从太平洋红豆杉树皮中提取的一种二萜类化合物，其细胞毒性被认为是通过稳定微管聚合束，从而干扰微管组装和细胞复制而发挥的。它对许多实体肿瘤显示出广泛的活性，包括卵巢癌、乳腺癌和子宫内膜癌。GOG报告紫杉醇对晚期宫颈鳞癌的有效率为17%。顺铂和紫杉醇的组合已经有效地用于治疗一些恶性肿瘤，目前正在进行各种鳞状细胞癌的研究，包括宫颈癌。本研究将确定与单独使用顺铂相比，顺铂联合紫杉醇是否能改善晚期宫颈鳞癌的有效率、无进展间期和/或生存率。此外，在标准治疗可能被视为姑息性治疗的临床环境中，这项研究将评估两种药物在毒性和/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.