Cyclosporine A, alpha-lnterferon and interleukin-2 following chemotherapy with BCNU, DTIC, cisplatin, and tamoxifen: a phase II study in advanced melanoma.
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.
Feun
Lynn
L
Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA. lfeun@med.miami.edu
Marini
Angela
A
Moffat
Frederick
F
Savaraj
Niramol
N
Hurley
Judith
J
Mazumder
Amitabha
A
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
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D016898:Interferon-alpha; D007376:Interleukin-2; D013629:Tamoxifen; D003606:Dacarbazine; D016572:Cyclosporine; D002945:Cisplatin; D002330:Carmustine