Intensive therapy with cisplatin, interleukin-2 and interferon-alpha-2a in patients with metastatic melanoma. A phase II Study.
OBJECTIVE
Based upon their individual clinical activity and combined effects in animal models or in vitro, we wished to evaluate a regimen of cisplatin, interferon-alpha, and IL-2 in patients with metastatic melanoma.


METHODS
Phase II pilot study.


METHODS
Referral-based US Government clinical research unit.


METHODS
Nine patients with metastatic malignant melanoma.


METHODS
Cisplatin 75-100 mg/m2 was administered intravenously over 30 minutes on days 1 and 8. Interferon-alpha 2a 5 Mu/m2 body surface area (BSA) was given subcutaneously for 4 days beginning 1 day before each dose of cisplatin. Beginning on day 15 and day 22, IL-2 was administered by intravenous continuous infusion at 3 Mu/m2 BSA/d for 96 hours and by daily intravenous bolus concurrent with daily subcutaneous doses of interferon-alpha 2a.


METHODS
Antitumor response and toxicities.


RESULTS
The study was stopped due to renal and hematopoietic toxicity and severe, delayed nausea and vomiting associated with the cisplatin-interferon treatment. Three of 9 patients achieved a partial response (duration 2.5, 4, 14+ months), and an additional patient had a 50% reduction in measurable tumor volume before undergoing resection of residual disease. Overall response rate was 45%.


CONCLUSIONS
This regimen was associated with excessive toxicity, and the lack of complete responses in a patient cohort with favorable characteristics for response (good performance status, predominance of skin and lymph node metastatic sites) suggests that it had no advantage over less toxic treatment regimens.


BACKGROUND
National Cancer Institute/Cancer Therapy Evaluation Program T89-0137.
Sznol
M
M
Clinical Research Branch, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21701.
Steis
R G
RG
Smith
J W
JW
Janik
J E
JE
Sharfman
W H
WH
Urba
W J
WJ
Fenton
R G
RG
Creekmore
S P
SP
Beveridge
J
J
Longo
D L
DL
D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D011994:Recombinant Proteins; D014839:Vomiting / Q000139:chemically induced
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins; D002945:Cisplatin