title: 13-cis retinoic acid in head and neck cancer chemoprevention: results of a randomized trial from the Italian Head and Neck Chemoprevention Study Group.
abstract: Patients with squamous cell carcinoma of the head and neck (HNSCC) after being treated radically remain at high risk for both recurrent and second primary tumours. 13-cis retinoic acid (13-cRA) was demonstrated to reverse pre-malignant lesions of the oral cavity and to reduce the incidence of second primary tumours in patients treated radically for HNSCC. Synergism between retinoids and interferon in tumoural cell lines have been demonstrated. Based on these data, the Italian Head and Neck Chemoprevention Study Group started a randomized chemoprevention study in patients radically treated for stage III and IV HNSCC. From February 1992 to January 1996, 267 patients were randomized: 126 were allocated to the control group, 126 were randomized to receive 13-cRA at a dose of 0.5 mg/kg per day per os and 15 patients have been assigned to the group of 13-cRA plus interferon alpha2a (IFN-alpha2a) at a dose of 3,000,000 UI 3 times a week (randomization in this arm interrupted due to administrative financial problems). The mean follow-up was 39 months. The 5-year actuarial survival was 58.9% for patients of the 13-cRA group and 57.2% for those of the control group (P=0.94). Among evaluable patients, disease progression was observed in 45 of 123 patients (36.6%) of the 13-cRA group and in 42 of 124 (33.9%) of the control group. The 5-year actuarial relapse-free survival was 48.9% for the 13-cRA group and 55.6% for the control group (P=0.62). Adverse effects, mostly of grade I were reported in 69.4% of treated patients (haematologic disorders, mucositis, conjunctivitis, cutaneous toxicity, hypertriglyceridemia and hypercholesterolemia). Only 5 patients (4.1%) reported grade III-IV toxicity. Low-dose of 13-cRA given for 1 year is ineffective as chemoprevention in patients with radically treated HNSCC.
authors.affiliation: Division of Oncology, Ospedale Casa Sollievo della Sofferenza, I-71013 San Giovanni Rotondo (FG), Italy. s.toma@operapadrepio.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Toma
authors.forename: Luigina
authors.initials: L
authors.lastname: Bonelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Sartoris
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mira
authors.forename: Antonio
authors.initials: A
authors.lastname: Antonelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Beatrice
authors.forename: Carlo
authors.initials: C
authors.lastname: Giordano
authors.forename: Marco
authors.initials: M
authors.lastname: Benazzo
authors.forename: Angelo
authors.initials: A
authors.lastname: Caroggio
authors.forename: Andrea Luigi
authors.initials: AL
authors.lastname: Cavalot
authors.forename: Sergio
authors.initials: S
authors.lastname: Gandolfo
authors.forename: Aldo
authors.initials: A
authors.lastname: Garozzo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Margarino
authors.forename: Guido
authors.initials: G
authors.lastname: Schenone
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Spadini
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sirotovà
authors.forename: Francesco
authors.initials: F
authors.lastname: Zibordi
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Balzarini
authors.forename: Italo
authors.initials: I
authors.lastname: Serafini
authors.forename: Piero
authors.initials: P
authors.lastname: Miani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cortesina
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D018890:Chemoprevention; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015474:Isotretinoin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015474:Isotretinoin