Forastiere A A, Urba S G
Department of Medical Oncology, Johns Hopkins Oncology Center, Baltimore, MD 21287-8936, USA.
Semin Oncol. 1995 Jun;22(3 Suppl 6):24-7.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and ifosfamide both have activity when evaluated as single agents in patients with advanced squamous cell carcinoma of the head and neck. The Eastern Cooperative Oncology Group completed the first phase II trial of paclitaxel in this population, observing a 40% response rate. Confirmatory trials are in progress in the United States and Europe. The Eastern Cooperative Oncology Group is currently evaluating high-dose (200 mg/m2) and low-dose (135 mg/m2) paclitaxel in combination with cisplatin to assess dose-response effects, toxicity, and efficacy. In an effort to identify an alternate to the cisplatin/5-fluorouracil regimen, investigators at Johns Hopkins and the University of Michigan are evaluating the combination of paclitaxel/ifosfamide. The regimen is paclitaxel 170 mg/m2 followed by ifosfamide 5 g/m2 divided over 3 days with mesna. Granulocyte colony-stimulating factor is started 24 hours after completion of the ifosfamide infusion. To date, 13 patients with recurrent and metastatic squamous cell carcinoma of the head and neck have been enrolled in the study. Eight patients have had prior chemotherapy as part of initial curative treatment or for recurrent disease. The best response observed in II evaluable patients is five partial responses, five stable diseases, and one disease progression. On progression, patients who have not been treated with cisplatin/5-fluorouracil receive that combination as second-line therapy. The occurrence of severe, life-threatening toxicity, primarily myelosuppression, has caused this study to be terminated. However, the responses observed have prompted an evaluation of the reverse sequence (ifosfamide followed by paclitaxel), which is now accruing patients.
紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）和异环磷酰胺在作为单药用于晚期头颈部鳞状细胞癌患者时均具有活性。东部肿瘤协作组完成了在该人群中进行的第一项紫杉醇II期试验，观察到缓解率为40%。美国和欧洲正在进行验证性试验。东部肿瘤协作组目前正在评估高剂量（200mg/m²）和低剂量（135mg/m²）紫杉醇联合顺铂，以评估剂量反应效应、毒性和疗效。为了找到顺铂/5-氟尿嘧啶方案的替代方案，约翰霍普金斯大学和密歇根大学的研究人员正在评估紫杉醇/异环磷酰胺的联合方案。该方案为紫杉醇170mg/m²，随后是异环磷酰胺5g/m²，分3天给药并加用美司钠。在异环磷酰胺输注完成24小时后开始使用粒细胞集落刺激因子。迄今为止，13例头颈部复发性和转移性鳞状细胞癌患者已纳入该研究。8例患者曾接受过化疗，作为初始根治性治疗的一部分或用于复发性疾病。在11例可评估患者中观察到的最佳反应为5例部分缓解、5例病情稳定和1例病情进展。病情进展时，未接受过顺铂/5-氟尿嘧啶治疗的患者接受该联合方案作为二线治疗。严重的、危及生命的毒性反应，主要是骨髓抑制的发生导致该研究终止。然而，观察到的反应促使对相反顺序（异环磷酰胺后接紫杉醇）进行评估，目前正在招募患者。
