Randomized phase III trial of neoadjuvant chemotherapy in head and neck cancer: 10-year follow-up.

In 1986, we initiated a multicenter, randomized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) with locoregional treatment alone in patients with head and neck squamous cell carcinoma. Here we report the long-term results of the trial. A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were randomly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment (group A) or locoregional treatment alone (group B). Among all patients, overall survival at 5 and 10 years was 23% (95% confidence interval [CI] = 15.3% to 30.9%) and 19% (95% CI = 11.6% to 26.4%), respectively, for those in group A and 16% (95% CI = 9.6% to 23.4%) and 9% (95% CI = 3.5% to 14.7%), respectively, for those in group B (P = .13). Among operable patients, we observed no difference between group A and group B in overall survival at 5 and 10 years (group A, 31% [95% CI = 14.9% to 47.3%] and 22.7% [95% CI = 7.1% to 38.3%], respectively; group B, 43.3% [95% CI = 25.6% to 61.0%] and 14.2% [95% CI = 0.1% to 28.3%], respectively; P = .73). Among inoperable patients, overall survival at 5 and 10 years was 21% (95% CI = 12.3% to 30.1%) and 16% (95% CI = 7.7% to 23.9%), respectively, for group A and 8% (95% CI = 1.5% to 12.3%) and 6% (95% CI = 0.1% to 9.1%), respectively, for group B (log-rank P = .04). Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease.

Neoadjuvant docetaxel, cisplatin, 5-fluorouracil before concurrent chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck versus concomitant chemoradiotherapy: a phase II feasibility study.

PURPOSE: To determine the feasibility of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CHT-RT) compared with the same CHT-RT regimen alone in locally advanced head-and-neck squamous cell carcinoma. METHODS AND MATERIALS: We treated 24 patients (20 men and 4 women) who had Stage III-IVM0 squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, or hypopharynx. The median patient age was 59 years (range, 41-73 years). The stage distribution was as follows: Stage II, 1 patient; Stage III, 6 patients; and Stage IV, 17; 18 patients had a performance status of 0 and 6 had a performance status of 1. None had undergone previous CHT or RT. Group 1 underwent three cycles of CHT (carboplatin area under the curve 1.5 on Days 1-4 and 5-fluorouracil 600 mg/m(2)/d continuous infusion for 96 h) starting on Days 1, 22, and 43 during RT (one daily fraction, 66-70 Gy within 33-35 fractions). Group 2 underwent three cycles of neoadjuvant TPF (docetaxel 75 mg/m(2), cisplatin 80 mg/m(2), 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) followed by the same CHT-RT regimen. RESULTS: After the first 16 patients, 8 in Group 1 and 8 in Group 2, the concomitant CHT-RT schedule was modified. The limiting toxicity observed during concomitant CHT-RT was similar in Groups 1 and 2, independent of neoadjuvant TPF administration. An excess of G3-G4 mucositis and other relevant toxicity that did not allowing completion of CHT-RT without interruption occurred in 44% of the patients. A reduction of at least one cycle of concurrent CHT was required in 31% of patients. On the basis of these data, the next 8 patients (Group 3) received three cycles of neoadjuvant TPF followed by two cycles only of CHT (cisplatin 20 mg/m(2) on Days 1-4 and 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) (PF) during Weeks 1 and 6 of the planned 7 weeks of RT. In Group 3, 25% of the patients developed World Health Organization G3-G4 mucositis. No World Health Organization hematologic G3-G4 toxicity was seen. RT interruption was required for 2 patients (25%). In 1 patient (12%), one cycle of CHT was omitted. During neoadjuvant TPF (Groups 2 and 3), the principal toxicities were G3-G4 neutropenia (37.5%) and G2 mucositis (44%). At the end of therapy, the CR rate was 62.5% for CHT-RT alone (Group 1) and 80% for neoadjuvant TPF followed by CHT-RT (Groups 2 and 3). CONCLUSION: Three cycles of neoadjuvant TPF followed by two cycles of PF during RT are feasible without limiting toxicity. Three cycles of TPF were well tolerated and did not compromise subsequent concomitant CHT-RT. A randomized multicenter Phase III study has been started with the aim of comparing two cycles of PF during RT as standard treatment vs. the experimental arm with three cycles of neoadjuvant TPF followed by two cycles of PF during RT.