title: Paclitaxel, cisplatin, and 5-fluorouracil in patients with advanced or recurrent squamous cell carcinoma of the head and neck: a preliminary report.
abstract: 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.
authors.affiliation: Department of Surgery, Veterans Administration Medical Center, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hussain
authors.forename: W
authors.initials: W
authors.lastname: Salwen
authors.forename: O
authors.initials: O
authors.lastname: Kucuk
authors.forename: J
authors.initials: J
authors.lastname: Ensley
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity; D010865:Pilot Projects
chemical_list: D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil