Randomized Phase III Trial of Neoadjuvant Chemotherapy in Head and Neck Cancer: 10-Year Follow-Up

Abstract

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.

Induction Chemotherapy for Head and Neck Cancer: Recent Data

“…The type of locoregional treatment did not influence the clinical benefits of induction chemotherapy. In a phase III trial conducted by the Gruppo di Studio sui Tumori della Testa e del Collo, patients received locoregional treatment with radiotherapy with or without surgery, either alone or preceded by four 21-day cycles of induction chemotherapy with cisplatin (100 mg/m 2 on day 1) and 5-FU (1,000 mg/m 2 per day, continuous infusion on days 1-5) [6,7]. There was no significant difference in the overall survival rate at 5 years and 10 years between the treatment arms for operable patients.…”

Sequential induction chemotherapy followed by radical chemo-radiation in the treatment of locoregionally advanced head-and-neck cancer

“…In contrast, the role of induction chemotherapy is not yet clear. Although not the standard of care, induction chemotherapy is used in clinical practice and is thought to be beneficial for reducing the rate of distant metastases (Paccagnella et al, 1994;Lefebvre et al, 1996), increasing organ preservation (Group, 1991;Lefebvre et al, 1996) and survival rates (Paccagnella et al, 1994;Zorat et al, 2004). Combining induction and concomitant chemotherapy with radiation, that is, in a sequential treatment approach, has the potential for improving disease outcomes.…”

The effect of induction chemotherapy followed by chemoradiotherapy in advanced head and neck cancer: a prospective study

“…These results are quite similar with a study by Paccagella et.al. 10 a randomized phase 2 Italian study. Two groups were compared: TPF followed by chemoradiotherapy versus chemo radiotherapy alone.…”