Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy in patients with locally advanced squamous cell carcinoma of the head and neck: the Dana Farber Cancer Institute experience.

BACKGROUND: The authors conducted a series of four Phase I-II trials of high-dose and intermediate-dose docetaxel, cisplatin, and 5-fluorouracil (TPF)-based induction chemotherapy for patients with advanced squamous cell carcinoma of the head and neck (SCCHN). The chemotherapy regimens and response rates for each trial were published previously. In the current analysis, the authors report the data on long-term survival, patterns of failure, and morbidity among the patients who were treated at their institution. METHODS: A total of 101 patients with previously untreated, locally advanced, curable SCCHN were entered onto the studies. Overall, 68 patients (67%) had N2-N3 disease, and 86 patients (85%) had Stage IV disease. Patients were treated with combinations of TPF with or without leucovorin. Cycles were repeated every 21-28 days for a total of 3 cycles followed by hyperfractionated radiotherapy. RESULTS: After a median follow-up of 49 months, 65 patients (64%) remain alive with no evidence of disease (NED), and 3 patients remain alive with disease, for an overall survival rate of 67% (68 patients). Twenty-six patients had locoregional recurrences (LRR), and 5 patients had both LRR and distant metastasis (DM). Only five patients had DM as the sole site of failure. Four patients underwent salvage surgery at the primary site and remain alive with NED. Excluding 17 patients with nasopharyngeal carcinoma, of 84 patients, 55 patients remain alive with NED (65%). Notably, 43 of 84 patients (51%) had oropharyngeal primary tumors, and 30 of those patients remain alive with NED (70%). Significant morbidity was low, with two treatment-related deaths. All but two of the surviving patients are able to swallow and had their feeding tubes removed. CONCLUSIONS: These data suggest that docetaxel adds incrementally to the efficacy of cisplatin and fluorouracil. Local-regional failures continue to be the major impediment to cure in these patients. Given the increase in local-regional dose intensity with chemoradiation, sequential treatment plans that integrate induction chemotherapy and chemoradiotherapy seem to be the logical next step.

A Phase I/II trial of concurrent docetaxel and radiation after induction chemotherapy in patients with poor prognosis squamous cell carcinoma of the head and neck.

BACKGROUND: The authors conducted a Phase I/II study in patients with a poor prognosis who had locally advanced squamous cell carcinoma of the head and neck (SCCHN) and who were treated initially with induction chemotherapy. Patients were treated with weekly docetaxel and concurrent daily fractionated radiation therapy to determine the maximum tolerated dose (MTD) of docetaxel and the efficacy of the regimen. METHODS: Twenty-two patients were enrolled, and 21 patients were treated. Eight patients had Stage III SCCHN, and 13 patients had Stage IV SCCHN without distant metastases and were treated first with 2-3 cycles of induction chemotherapy, which consisted of cisplatin plus 5-fluorouracil with or without leucovorin. Patients with a poor prognosis were identified as those who achieved a partial response to induction treatment, achieved a complete response with a positive biopsy, or were at high risk for developing recurrent disease. Patients were treated subsequently with concurrent, escalating doses of docetaxel (given weekly x 6) and once daily 200-centigray radiation fractions. RESULTS: Three patients were treated with a weekly docetaxel dose of 20 mg/m(2) without dose-limiting toxicity (DLT). Both patients who were treated at the next dose level of 30 mg/m(2) experienced DLT. A dose of 25 mg/m(2) was studied without DLT in the 16 patients who were treated, establishing this as the MTD. Sixty-seven percent of the patients are alive without disease at a median follow-up of 35 months (range, 12-59 months) after the initiation of chemoradiotherapy. CONCLUSIONS: The MTD of weekly docetaxel with concurrent daily radiation therapy in the postinduction setting was 25 mg/m(2). Disease free survival data from this study were good and indicated that this regimen was effective in the treatment of patients with SCCHN who had a poor prognosis.