title: Phase 2 study of intratumoral cisplatin and epinephrine treatment for locally recurrent head and neck tumors.
abstract: Local relapses of head and neck tumors are not often eligible for surgical and/or radiotherapy retreatment, and the efficacy of systemic chemotherapy is poor. A greater accumulation and efficacy of anticancer drugs with lower systemic toxicity is theoretically obtained with intratumoral chemotherapy. In experimental studies, epinephrine has been shown to increase the concentration and antitumor effect of intratumoral cisplatin. Fourteen patients with locally recurrent head and neck tumors (median age, 58.7 years) were included in this phase 2 trial. Recurrent tumors (squamous cell carcinomas) were located on the tongue, oral pharynx, or cervical nodes. Prior therapy was surgery and/or radiotherapy with or without intravenous chemotherapy. Inclusion criteria included an Eastern Cooperative Oncology Group/World Health Organization performance status of 0, 1, or 2, an anticipated survival of >3 months, adequate cardiac, kidney, liver, and bone marrow function, and no coagulopathy or carotid invasion. Fifty intratumoral injections of cisplatin-epinephrine (average, 3.6 injections per patient; range, 1 to 5 injections) were given to the 14 patients from November 1998 to July 2000. Patients were treated with cisplatin (1 mg/mL; maximum dose, 50 mg) at an injection volume corresponding to the tumor volume (1 mL/cm3 of tumor; maximum volume, 50 mL). Epinephrine was added at a concentration of 0.02 mg/mL. Intratumoral injections were repeated every 2 to 3 weeks at different locations in the tumors to obtain a homogeneous distribution. Tumor response was evaluated by clinical examination and computed tomography. Eight objective responses were registered among the 14 patients. Four were complete responses, and 4 were partial responses. The average time to disease progression was 11.5 +/- 8.9 weeks. Local adverse effects were transient pain, swelling, and erythema at the site of the injection. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Intratumoral injection of cisplatin and epinephrine in an aqueous solution has a definite antitumor activity in recurrent head and neck cancer with acceptable local tolerance and no major systemic toxic effects except for transient tachycardia and high blood pressure at the time of injection.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hôpital Général, Dijon, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Duvillard
authors.forename: Philippe
authors.initials: P
authors.lastname: Romanet
authors.forename: Alain
authors.initials: A
authors.lastname: Cosmidis
authors.forename: Nathalie
authors.initials: N
authors.lastname: Beaudouin
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000627:therapeutic use*; D004357:Drug Synergism; D004837:Epinephrine / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015552:Injections, Intralesional; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014662:Vasoconstrictor Agents; D002945:Cisplatin; D004837:Epinephrine