title: Combined chemoimmunotherapy of metastatic melanoma: a single institution experience.
abstract: The addition of cytokines, such as interferon alpha-2b and interleukin-2, to chemotherapy in metastatic melanoma has produced conflicting results in phase II and III trials. We report our experience with a chemoimmunotherapeutic regimen using subcutaneous cytokines. Twenty-eight patients with advanced melanoma (median age, 45 years; male to female ratio, 19 : 9) were treated. Doses were as follows: cisplatin, 20 mg/m intravenously (iv) days 1-4; vinblastine, 1.6 mg/m iv days 1-4; dacarbazine, 800 mg/m iv day 1; interferon alpha-2b, 5 MIU/m subcutaneously (sc) days 1-5; interleukin-2, 9 MIU/m sc days 1-5 and 8-12. Treatment was repeated every 3 weeks for a maximum of six cycles. The response was assessed after two cycles and toxicity at every cycle, according to World Health Organization (WHO) and National Cancer Institute (NCI) criteria, respectively. At a median follow-up of 8 months, only four patients (14%) were still alive. The overall response rate was 33%, with three (11%) complete responses lasting for 17, 14 and >24 months. There were six (22%) partial responses and three stable disease. Amongst the responders, three patients progressed at the level of the central nervous system. The median time to progression and overall survival were 3.5 and 9 months, respectively. The most common grade 3-4 toxicity was neutropenia, reported in 25 of the 28 patients (92%). Only two patients (7%) experienced neutropenic fever. Thrombocytopenia grade 3-4 occurred in seven of the 28 patients (25%), with only one patient needing transfusional support. One toxic death due to neutropenic fever occurred. It can be concluded that the chemoimmunotherapy schedule evaluated is active and may be considered for patients with metastatic melanoma who have a good performance status and a limited disease burden.
authors.affiliation: Division of Medical Oncology C, Centro di Riferimento Oncologico, Aviano, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Lauro
authors.forename: Simona
authors.initials: S
authors.lastname: Scalone
authors.forename: Nicoletta
authors.initials: N
authors.lastname: La Mura
authors.forename: Martina
authors.initials: M
authors.lastname: Zanetti
authors.forename: Paola
authors.initials: P
authors.lastname: Nigri
authors.forename: Andrea
authors.initials: A
authors.lastname: Freschi
authors.forename: Andrea
authors.initials: A
authors.lastname: Veronesi
mesh_terms: 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 / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D014747:Vinblastine / Q000008:administration & dosage; D014839:Vomiting / Q000139:chemically induced
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D014747:Vinblastine; D003606:Dacarbazine; D002945:Cisplatin