title: Cyclosporine A, alpha-lnterferon and interleukin-2 following chemotherapy with BCNU, DTIC, cisplatin, and tamoxifen: a phase II study in advanced melanoma.
abstract: Preclinical data suggest that one method of inducing autoimmunity to tumor is the administration and subsequent withdrawal of cyclosporine A following chemotherapy and that this effect may be enhanced with interferon and interleukin-2. Consequently, we performed a phase II trial in patients with advanced melanoma to explore this approach. Thirty-three patients were treated with BCNU (150 mg/m2 iv every 8 weeks), cisplatin (25 mg/m2 iv days 1-3) every 4 weeks, DTIC (220 mg/m2 iv days 1-3 every 4 weeks) along with tamoxifen (10 mg po BID days 1-4). Cyclosporine A at 3 mg/kg/day in two divided doses was given on days 4-21, alpha-interferon 1 million units/m2 subcutaneously every other day on days 4-21 and interleukin-2 1 million units/m2 BID subcutaneously days 21-28 were also given. Of the 33 patients, 3 patients (9%) had complete response and 8 patients (24%) had a partial response for a total response rate of 33% (95% confidence interval 18-52%). Median duration of response was 17 months (range 3+ to 24+ months). Six patients continue to show no signs of tumor progression for 3+, 5+, 10+, 24+, 60+, and 72+ months. Toxicity was generally well tolerated and included myelosuppression and fatigue. This regimen is feasible and generally tolerable and has produced an antitumor response rate comparable with inpatient biochemotherapy regimens.
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA. lfeun@med.miami.edu
authors.forename: Lynn
authors.initials: L
authors.lastname: Feun
authors.forename: Angela
authors.initials: A
authors.lastname: Marini
authors.forename: Frederick
authors.initials: F
authors.lastname: Moffat
authors.forename: Niramol
authors.initials: N
authors.lastname: Savaraj
authors.forename: Judith
authors.initials: J
authors.lastname: Hurley
authors.forename: Amitabha
authors.initials: A
authors.lastname: Mazumder
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002330:Carmustine / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use; D016572:Cyclosporine / Q000009:adverse effects*; D003606:Dacarbazine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016898:Interferon-alpha / Q000009:adverse effects; D007376:Interleukin-2 / Q000009:adverse effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D012878:Skin Neoplasms / Q000188:drug therapy*; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D013629:Tamoxifen; D003606:Dacarbazine; D016572:Cyclosporine; D002945:Cisplatin; D002330:Carmustine