AbstractStandard treatment of locally advanced laryngeal, hypopharyngeal, and some oropharyngeal cancers includes total laryngectomy. In an attempt to preserve the larynx through induction chemotherapy, we conducted two consecutive phase II studies. From March 1986 to February 1991, 64 patients with advanced untreated but resectable head and neck cancer who would require total laryngectomy were enrolled on one of two cisplatin‐based induction regimens: cisplatin‐bleomycin‐5‐fluorouracil (PBF) in 31 patients and cisplatin‐5‐fluorouracil (PF) in 33; all received definitive radiotherapy. Surgery was reserved for patients who achieved less than a partial response to chemotherapy and patients with residual or recurrent disease after sequential chemotherapy plus radiotherapy. Overall complete plus partial response rates to both cisplatin‐based regimens were comparable. The combined PF and PBF overall response rates were 75% for laryngeal cancer, 78% for hypopharyngeal cancer, and 75% for oropharyngeal cancer. Complete response rates after radiotherapy were 88%, 83%, and 50%, respectively. Neutropenia (<1,000 cells/mm3) was the most common hematologic toxic effect: it occurred in 44% of patients who received PF and 16% of those who received PBF. Grade ≥3 mucositis occurred in 50% of patients who received PF and 4% who received PBF. The data suggest that laryngeal preservation was feasible in all three primary‐site subgroups. With followup of 15+ to 54+ months, 44% of patients with laryngeal cancer, 28% with hypopharyngeal cancer, and 22% with oropharyngeal cancer are alive with laryngeal preservation. The overall 2‐year survival rates for patients with cancer of the larynx, hypopharynx, and oropharynx were 71%, 46%, and 38%, respectively. © 1994