Induction chemotherapy in head and neck cancer: Results of a phase III trial

Abstract

Between December 1982 and October 1986, 131 patients with stage II-III-IV squamous cell carcinoma of the oropharynx or oral cavity were randomized to induction chemotherapy, consisting of bleomycin (10 mg/m2/day in continuous infusion from day 1 to day 5), methotrexate (120 mg/m2 on day 2) followed by folinic acid, 5-fluorouracil (5 FU) (600 mg/m2 on day 2), and cisplatin (120 mg/m2 on day 4) every 4 weeks for a total of three cycles followed by definitive locoregional treatment versus locoregional treatment alone. The modalities of definitive treatment (radiotherapy +/- surgery) were chosen prior to randomization. A total of 116 patients were evaluable. Of 55 patients in the chemotherapy arm, four (7%) had a complete response (CR) and 23 (42%) a partial response (PR) following the induction regimen. At the completion of locoregional treatment, 76% (42 of 55) of patients in the experimental group were in CR compared to 89% (54 of 61) in the control group. There was no difference in survival, cause-specific survival, and pattern of relapse between both groups. The median survival was 22 months in the chemotherapy group and 29 months in the control group. Responders to chemotherapy did not fare better than nonresponders. Chemotherapy-related toxicities were few and most of them related to cisplatin which was reduced to 100 mg/m2 for 35 patients. There were no treatment-related deaths and, in the experimental arm of the trial, no increased morbidity from locoregional treatment. This induction regimen does not offer any advantages over standard treatment.

Induction chemotherapy and radiation therapy for T4 oropharyngeal carcinoma

“…The response of the primary lesion to induction chemotherapy in this study (29% CR, 52% PR) agrees with previously published studies [1,2,13,14,29]. As reported by others [14], there was no difference in local control for patients who had CR at the primary site compared with those who had PR.…”

“…Therefore, patients with neck stage N2-N3 may be more likely to benefit from induction chemotherapy than are patients with neck stage N0 − N1. Most patients (48%-78%) in the prospective randomized studies had N0-N1 neck stage and were at relatively low risk for developing distant metastases [11,[13][14][15]. Patients most likely to benefit from induction chemotherapy may be those with AJCC stage IV tumors (T4 and/or N2-N3), but most studies evaluating induction chemotherapy have included stage III tumors.…”

“…Therefore, it may be beneficial to treat stage T4 oropharyngeal lesions with induction chemotherapy because they have a < 50% local control rate when treated with radiation alone; and it may not be beneficial to treat stage T3 oropharyngeal lesions with induction chemotherapy because they have a 65%-70% local control rate when treated with radiation therapy alone [20]. Most patients (62%-95%) in the prospective randomized studies evaluating induction chemotherapy had stage T3 or smaller primary lesions and therefore were at relatively low risk for local-regional failure [11,[13][14][15], which would make it more difficult to detect a potential benefit from induction chemotherapy. Patients with stage N0 − N1 neck disease have a distant metastasis rate of Յ 10%, whereas patients with stage N2-N3 disease have a distant metastasis rate of 20%-30% [21].…”

Survival Impact of Planned Restaging and Early Surgical Salvage Following Definitive Chemoradiation for Locally Advanced Squamous Cell Carcinomas of the Oropharynx and Hypopharynx

“…Despite repeated evaluation, since the 1970s, studies of induction chemotherapy have failed to demonstrate a significant LC or survival benefit. [7][8][9][10][11][12][13][14][15] In contradistinction, recent studies clearly demonstrate a survival benefit for concurrent chemoradiation therapy in comparison with RT alone. 16 -20 Many nonsurgical organ preservation protocols have also justified the use of induction chemotherapy to reduce distant metastases, in addition to selecting patients for nonsurgical therapy as described earlier, but this strategy may be of questionable benefit based on the results of RTOG 91-11, which indicate a reduced survivorship in patients experiencing initial local failure and no benefit from induction therapy.…”

Chemotherapy and Biologic Therapy for Squamous Cell Cancers of the Head and Neck

“…[4][5][6][7][8][9][10][11] Chemotherapy regimens were mainly cisplatin based combinations with cisplatin and 5-FU dominating the literature in the 1990s. In spite of high antitumor activity of the induction chemotherapy, all but two trials did not show a benefit of induction chemotherapy for locoregional control or overall survival.…”