title: Multicenter phase II study of chemoimmunotherapy in the treatment of metastatic melanoma.
abstract: Combining chemotherapy and immunotherapeutic agents such as interleukin-2 and interferon alpha-2b might improve treatment results in metastatic melanoma (MM) patients compared with chemotherapy alone. This prospective study evaluated the potential efficacy of a biochemotherapy regimen followed by maintenance biotherapy for the treatment of MM. Twenty-two patients with stage IV melanoma were treated for 5 consecutive days with cisplatin at 20 mg/m, vinblastine at 1.6 mg/m, and dacarbazine at 160 mg/m. Pegylated interferon alpha-2b at a dose of 50 microg every week, subcutaneous interleukin-2, 1.8 MIU, and oral 13-cis-retinoic acid (13-cis-RA) at 0.5 mg/kg were given 5 days/week for 3 weeks each month during the period of chemotherapy administration. Maintenance biotherapy was continued in patients who had a complete or partial response or disease stability (clinical benefit) after six courses of biochemotherapy. The primary endpoint was response; secondary endpoints were the evaluation of the immunologic parameters, toxicity, progression-free survival, and overall survival. Twelve patients (54.5%) achieved a response, and seven (31.8%) maintained stable disease for at least 6 months with maintenance biotherapy. The median progression-free survival and overall survival were 23.3 and 45.7 months, respectively. The most important toxicities from chemotherapy were grades 3 and 4 neutropenia and thrombocytopenia in 41 and 18% of patients, respectively, whereas grade 2 autoimmune reactions were observed in 21% of patients after maintenance biotherapy. A prolonged enhancement of immunologic function was observed in the 19 patients treated with maintenance therapy. A regimen of six cycles of biochemotherapy followed by maintenance immunotherapy is well tolerated, and shows significant activity in patients with MM.
authors.affiliation: ALS-1 Civilian Hospital, Avezzano, Oncology Division, Monterotondo, Roma. frecchia1946@libero.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Recchia
authors.forename: Giampiero
authors.initials: G
authors.lastname: Candeloro
authors.forename: Stefano
authors.initials: S
authors.lastname: Necozione
authors.forename: Luca
authors.initials: L
authors.lastname: Fumagalli
authors.forename: Massimo
authors.initials: M
authors.lastname: Bratta
authors.forename: Silvio
authors.initials: S
authors.lastname: Rea
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004358:Drug Therapy / Q000379:methods; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D015474:Isotretinoin / Q000008:administration & dosage; D008278:Magnesium Sulfate / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011446:Prospective Studies; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D014747:Vinblastine; D008278:Magnesium Sulfate; D003606:Dacarbazine; D003907:Dexamethasone; D015474:Isotretinoin; D002945:Cisplatin; C100416:peginterferon alfa-2a