ten Bokkel Huinink W, Veenhof C, Helmerhorst T, Bierhorst F, Dalesio O, Winograd B, Depauw L, Pinedo H M
European Cancer Center, Amsterdam, The Netherlands.
Semin Oncol. 1995 Jun;22(3 Suppl 6):97-100.
Second-line treatment with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) may achieve remissions in patients suffering from ovarian cancer who have failed primary chemotherapy with cisplatin- or carboplatin-based regimens. Introduction of paclitaxel in combination with cisplatin into the first-line treatment strategy was therefore the next logical step in the development of chemotherapy against ovarian cancer. Data already have shown that this may result in better survival. Since carboplatin may replace cisplatin, the combination of paclitaxel with carboplatin seemed a further necessary step. We therefore embarked on a dose-finding study of paclitaxel and carboplatin. Fourteen patients with International Federal of Gynecology and Obstetrics stage III and IV ovarian cancer with a median age of 55.5 years entered this study of escalating doses of either carboplatin or paclitaxel. Doses of carboplatin could be escalated from 300 to 450 mg/m2 and paclitaxel could be escalated from 125 to 175 mg/m2 without dose-limiting myelosuppression. At the highest dose level reported here, only transient short-lived leukopenia was observed. Other toxicities consisted of nausea and vomiting, peripheral neurotoxicity, and arthralgia, all mild. In the first 14 patients, 10 of whom are evaluable, complete remissions were seen in two patients and partial remissions in six. This study will escalate the doses of paclitaxel and carboplatin further. This treatment is well tolerated and yields satisfactory antitumor results.
对于接受以顺铂或卡铂为基础的一线化疗失败的卵巢癌患者，使用紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）进行二线治疗可能会实现缓解。因此，将紫杉醇与顺铂联合应用于一线治疗策略是卵巢癌化疗发展中的下一步合理举措。已有数据表明，这可能会带来更好的生存率。由于卡铂可替代顺铂，紫杉醇与卡铂联合似乎是进一步必要的步骤。因此，我们开展了一项紫杉醇和卡铂的剂量探索研究。14例国际妇产科联盟（FIGO）III期和IV期卵巢癌患者，中位年龄55.5岁，进入了这项关于递增卡铂或紫杉醇剂量的研究。卡铂剂量可从300mg/m²递增至450mg/m²，紫杉醇剂量可从125mg/m²递增至175mg/m²，且无剂量限制性骨髓抑制。在本文报道的最高剂量水平，仅观察到短暂的白细胞减少。其他毒性包括恶心、呕吐、外周神经毒性和关节痛，均较轻微。在最初的14例患者中，10例可评估，2例患者出现完全缓解，6例患者出现部分缓解。本研究将进一步递增紫杉醇和卡铂的剂量。这种治疗耐受性良好，且产生了令人满意的抗肿瘤效果。
