title: Biochemotherapy with temozolomide, cisplatin, vinblastine, subcutaneous interleukin-2 and interferon-alpha in patients with metastatic melanoma.
abstract: The aim of this study was to determine the efficacy and tolerability of a biochemotherapy regimen, including low-dose subcutaneous interleukin-2 and temozolomide, in patients with metastatic melanoma. Treatment consisted of temozolomide (150 mg/m per day on days 1-5), cisplatin (20 mg/m per day intravenously on days 1-4), vinblastine (1.5 mg/m per day on days 1-4), interleukin-2 (4.5 MU/m per day subcutaneously on days 5-8) and interferon-alpha2b (5 MU subcutaneously on days 5-9, 11, 13, 15, every 28 days). Thirty-six patients were included. Patients with poor prognostic factors were not excluded. Seventeen patients (47%) had been treated previously in an adjuvant setting with interferon-alpha. Four patients (11%) had been treated previously with chemotherapy and six (17%) had been treated with other biochemotherapy regimens. The distribution by American Joint Committee on Cancer staging was as follows: M1a in two patients (6%), M1b in 11 patients (31%) and M1c in 23 patients (64%). At inclusion, seven patients (19.4%) had cerebral metastases that had previously been treated with whole brain radiotherapy. For thirty-four evaluable patients, seven (20.5%) achieved an objective response. Overall, metastatic disease was substantially decreased or temporarily stabilized in 11 patients (32.4%; 95% confidence interval, 17.4-50.5). Responses were observed for all locations. The central nervous system was the initial site of relapse in two responding patients. The median survival was 10 months. The main toxicities noted were haematological (grades 3-4): neutropenia (1.8%), thrombocytopenia (1.8%) and anaemia (1.2%). It can be concluded that this regimen is well tolerated and has a modest activity despite the poor prognosis of our patient population. The low haematological toxicity rate obtained suggests that higher doses could be tried.
authors.affiliation: Medical Oncology Department, Clinic Institute of Hematologic and Oncologic Diseases (ICHMO), Clinic Hospital, Barcelona, Spain. mgocao@unav.es
authors.forename: María
authors.initials: M
authors.lastname: González Cao
authors.forename: Joseph
authors.initials: J
authors.lastname: Malvehy
authors.forename: Rosa
authors.initials: R
authors.lastname: Martí
authors.forename: Carlos
authors.initials: C
authors.lastname: Conill
authors.forename: Marcelo
authors.initials: M
authors.lastname: Sánchez
authors.forename: Marta
authors.initials: M
authors.lastname: Martín
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrera
authors.forename: Joseph
authors.initials: J
authors.lastname: Herrero
authors.forename: Pere
authors.initials: P
authors.lastname: Gascón
authors.forename: Begona
authors.initials: B
authors.lastname: Mellado
authors.forename: Teresa
authors.initials: T
authors.lastname: Castel
authors.forename: Susana
authors.initials: S
authors.lastname: Puig
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy / Q000473:pathology; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin; D000077204:Temozolomide