Larynx Preservation in Pyriform Sinus Cancer: Preliminary Results of a European Organization for Research and Treatment of Cancer Phase III Trial

• Published in: JNCI : Journal of the National Cancer Institute 1996-07, Vol.88 (13), p.890-899
• Main Authors: Lefebvre, Jean-Louis, Chevalier, Dominique, Luboinski, Bernard, Kirkpatrick, Anne, Collette, Laurence, Sahmoud, Tarek
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Cancer; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Medical sciences; Pharmacology. Drug treatments; Throat
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/88.13.890

Background: As a general rule, surgery whenever possible, followed by irradiation is considered to be the standard treatment for cancer of the hypopharynx, thus sacrificing natural speech. In most patients, surgery includes removal of the larynx. Purpose: A prospective, randomized phase III study was conducted by the European Organization for Research and Treatment of Cancer (EORTC) starting in 1990 to compare a larynx-preserving treatment (induction chemotherapy plus definitive, radiation therapy in patients who showed a complete response or surgery in those who did not respond) with conventional treatment (total laryngectomy with partial pharyngectomy, radical neck dissection, and postoperative irradiation) in previously untreated and operable patients with histologically proven squamous cell carcinomas of the pyriform sinus or aryepiglottic fold, but free of other cancers. Methods: Patients were randomly assigned to one of two treatment arms: 1) immediate surgery with postoperative radiotherapy (50–70 Gy) or 2) induction chemotherapy (cisplatin [100 mg/m2] given as a bolus intravenous injection on day 1, followed by infusion of fluorouracil [1000 mg/m2 per day] on days 1–5). An endoscopic evaluation was performed after each cycle of chemotherapy. After two cycles, only partial and complete responders received a third cycle. Patients with a complete response after two or three cycles of chemotherapy were treated thereafter by irradiation (70 Gy); nonresponding patients underwent conventional surgery with postoperative radiation (50–70 Gy). Salvage surgery was also performed when patients relapsed after chemotherapy and irradiation. The trial was designed to test the equivalence of the two treatment arms; i.e., the induction chemotherapy treatment would be judged equivalent to immediate surgery if the relative risk of death for induction chemotherapy compared with immediate surgery was significantly less than 1.43 using a one-sided hypothesis test at the.05 level of significance. Results: Two hundred two patients entered the trial and were randomly assigned; only 194 were eligible for treatment (94 in the immediate-surgery arm and 100 in the induction-chemotherapy arm). In the induction-chemotherapy arm, complete response was seen in 52 (54%) of 97 patients with local disease (primary tumor) and in 31 (51%) of 61 patients with regional disease (involvement of the neck). Treatment failures at local, regional, and second primary sites occurred at approximat