Phase II study of paclitaxel, ifosfamide, and carboplatin in patients withrecurrent or metastatic head and neck squamous cell carcinoma

BACKGROUND, In the current study the authors assessed the antitumor activit y (including response rate, duration of response, and survival) and toxicit y profile (including anorexia, fatigue, emesis, and peripheral neuropathy) of a combination of paclitaxel, ifosfamide, and carboplatin (TIC) in patien ts with recurrent or metastatic squamous cell carcinoma of the head and nec k (SCCHN). The trial hypothesis was that the TIC therapeutic index would be as high as that of paclitaxel, ifosfamide, and cisplatin (TIP) in this set ting, but with less toxicity, METHODS. Patients with recurrent or metastatic SCCHN were treated with 175 mg/m(2) of paclitaxel as a 3-hour infusion on Day 1, 1000 mg/m(2) of ifosfa mide as a 2-hour infusion on Days 1-3, 600 mg/m(2) of mesna on Days 1-3, an d carboplatin (area under the concentration-time curve of 6) as a 30-minute infusion on Day 1; the regimen was repeated every 3-4 weeks. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine befor e paclitaxel infusion. Prophylactic hematopoietic growth factors were not g iven. RESULTS. Among 56 patients entered onto the study, 55 patients were analyze d for survival rates (locoregional recurrence alone in 56% of patients and distant metastasis with Or without locoregional recurrence in 44% of patien ts). Fifty-four patients were evaluable for tumor response and toxicity. A total of 32 patients (59%) had disease that responded to treatment; the com plete response rate was 17% (9 of 54 patients). The median duration of the responses was 3.7 months (95% confidence interval [95% CI], 3.4-7.8 months) and that of complete responses was 9.7 months (95% CI, 7.4 months to date of last follow-up). The median duration of follow-up care in all patients w as 13.5 months. The median survival time for all patients was 9.1 months (9 5% Ct, 7.9-12.2 months). The regimen was well tolerated. Neutropenic fever developed in 30% of the patients; 1 patient died of neutropenia and sepsis. Other toxic effects included Grade 2-3 anorexia in 13% of patients, Grade 2-3 weight loss in 11% of patients, Grade 2-3 fatigue in 27% of patients, G rade 2-3 nausea/emesis in 13% of patients, and Grade 2-3 peripheral neuropa thy in 9% of patients (toxicity grading based on the National Cancer Instit ute's Common Toxicity Criteria). Red blood cell and platelet transfusions w ere required in 13% and 7% of patients, respectively. CONCLUSIONS, The TIC regimen had high antitumor activity in patients with r ecurrent or metastatic SCCHN, with a 59% major response rate (17% complete response rate with relatively durable complete responses). Neutropenic feve r developed in 30% of the patients, the incidence of which might have been decreased by prophylactic antibiotics or hematopoietic growth factor suppor t. Other toxic effects included significantly lower rates and less severe i nstances of anorexia, emesis, fatigue, and peripheral neuropathy than those reported with the previously studied TIP regimen. The TIC regimen currentl y is being studied as an induction chemotherapy regimen in previously untre ated patients with locally advanced SCCHN. The activity of TIC (a novel pac litaxel and ifosfamide-based regimen) in patients with recurrent or metasta tic SCCHN should be confirmed in a Phase III randomized trial. (C) 2000 Ame rican Cancer Society.