Hussain M, Salwen W, Kucuk O, Ensley J
Department of Surgery, Veterans Administration Medical Center, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-43-S19-45.
The combination of 5-fluorouracil (5-FU) and cisplatin is considered the most active chemotherapy for patients with recurrent squamous cell carcinoma of the head and neck (SCCHN), with an overall response rate of 30%. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated activity in SCCHN and synergy with cisplatin. To augment the activity of the combination of 5-FU and cisplatin, a pilot study was designed to determine the feasibility of combining 3-hour infusional paclitaxel with 5-FU and cisplatin. To be eligible, patients had to have recurrent or advanced SCCHN with measurable or evaluable disease and no prior chemotherapy. A minimum of three courses had to be delivered to determine cumulative toxicity. The starting dose level consisted of paclitaxel 135 mg/m2 on day 1, cisplatin 75 mg/m2 on day 2, and 5-FU 1 g/m2 on days 2 through 6. The first treated patient developed grade 4 mucositis, which resulted in reducing dose level 1 of 5-FU to 800 mg/m2/d on days 2 through 6 (seven patients); subsequently, the 5-FU dose was adjusted to 1 g/m2/d on days 2 through 5 (nine patients). To date, 17 patients have been enrolled, with a median age of 62 years (range, 48 to 75 years). Of the 17 patients, nine had recurrent disease following prior surgery and/or radiotherapy and eight had previously untreated advanced SCCHN. Major toxicities were neutropenia and mucositis. There were four early deaths (two treatment-related and two cancer-related). Forty-seven courses of therapy were delivered, with a median of two (range, one to five). The overall response rate in 14 response-evaluable patients was 71% (10 of 14 patients; eight partial and two complete responses). Five of seven response-evaluable patients with recurrent disease had major responses (one complete and four partial responses). At the current dose, the combination of paclitaxel/5-FU/cisplatin is feasible and shows very encouraging activity, particularly in patients with recurrent SCCHN.
5-氟尿嘧啶（5-FU）和顺铂联合用药被认为是复发性头颈部鳞状细胞癌（SCCHN）患者最有效的化疗方案，总体缓解率为30%。紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）已证明对SCCHN有活性且与顺铂有协同作用。为增强5-FU和顺铂联合用药的活性，设计了一项初步研究以确定3小时输注紫杉醇与5-FU和顺铂联合使用的可行性。符合条件的患者必须患有复发性或晚期SCCHN且疾病可测量或可评估，并且未曾接受过化疗。必须至少给予三个疗程以确定累积毒性。起始剂量水平为第1天给予紫杉醇135mg/m²，第2天给予顺铂75mg/m²，第2至6天给予5-FU 1g/m²。首位接受治疗的患者出现4级粘膜炎，这导致第2至6天5-FU的剂量水平1降至800mg/m²/天（7例患者）；随后，5-FU剂量在第2至5天调整为1g/m²/天（9例患者）。迄今为止，已纳入17例患者，中位年龄为62岁（范围48至75岁）。在这17例患者中，9例在先前手术和/或放疗后患有复发性疾病，8例先前未接受治疗的晚期SCCHN。主要毒性为中性粒细胞减少和粘膜炎。有4例早期死亡（2例与治疗相关，2例与癌症相关）。共进行了47个疗程的治疗，中位疗程数为2个（范围1至5个）。14例可评估缓解的患者总体缓解率为71%（14例患者中的10例；8例部分缓解和2例完全缓解）。7例可评估缓解的复发性疾病患者中有5例有主要缓解（1例完全缓解和4例部分缓解）。在当前剂量下，紫杉醇/5-FU/顺铂联合用药是可行的，并且显示出非常令人鼓舞的活性，特别是在复发性SCCHN患者中。
