title: Radiotherapy with concomitant continuous cisplatin infusion for unresectable tumors of the upper aerodigestive tract: results of a phase I study.
abstract: A phase I-II study was initiated in February 1991 of concomitant radiation and cisplatin (CDDP) in the treatment of unresectable head and neck squamous cell carcinomas (n = 12). The first patient was treated palliatively for a cervical recurrence of laryngeal cancer. The 11 other patients had locally advanced (stage IV) previously untreated carcinomas of the oropharynx (n = 9), hypopharynx (n = 1), or cervical node with unknown primary site (n = 1). Standard external radiation was carried out up to a total dose of 60 Gy/6 weeks (7 MeV electron beam) for the first patient and 72 Gy/8 weeks (Co60 beam) for the other 11 patients. CDDP was infused continuously during the entire radiation treatment, 5 days/week. The starting dose was 4 mg/m2/day and was escalated by increments of 1 mg/m2/day; dose-limiting toxicity was observed at 7 mg/m2/day. Neutropenia (grade 4, one patient; grade 3, three patients) and thrombocytopenia (grade 3, one patient; grade 2, one patient) were the limiting factors. Therefore, the recommended dose of CDDP is 6 mg/m2/day. All patients but one completed the scheduled radiation. For the entire group, mucositis was not more severe than that observed with radiotherapy alone. There was no nephro-, oto-, or neurotoxicity. A complete response was obtained in eight (66%) patients. Of these, four were free of disease 12-34 months after completion of treatment and one had a total glossectomy for a tongue necrosis. For the whole series, the mean overall survival was 16 months posttreatment. Pharmacokinetic analysis indicated the total cisplatin accumulation at the end of treatment to be 743-1551 ng/ml. Accumulation of ultrafilterable platin was noted in only one patient (137 ng/ml at the end of treatment).
authors.affiliation: Department of Radiotherapy, C.H.U. Rangueil, Toulouse, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Bachaud
authors.forename: E
authors.initials: E
authors.lastname: Chatelut
authors.forename: P
authors.initials: P
authors.lastname: Canal
authors.forename: N
authors.initials: N
authors.lastname: Albin
authors.forename: E
authors.initials: E
authors.lastname: Yardeni
authors.forename: J M
authors.initials: JM
authors.lastname: David
authors.forename: E
authors.initials: E
authors.lastname: Serrano
authors.forename: N
authors.initials: N
authors.lastname: Daly-Schveitzer
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D002945:Cisplatin