CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium.
BACKGROUND
CCI-779 is an analog of the immunosuppressive agent, rapamycin, that has demonstrated activity against melanoma in preclinical models and shown clinical benefit in patients with breast and renal carcinoma. CCI-779 is not immunosuppressive when administered on an intermittent schedule, and its toxicity is modest, consisting of nausea, diarrhea, hypertriglyceridemia, thrombocytopenia, asthenia, and follicular dermatitis.


METHODS
The current trial was designed to detect a median time to disease progression of >18 weeks in patients with metastatic melanoma treated with a 250-mg weekly dose of CCI-779 administered intravenously after diphenhydramine premedication. Patients with measurable disease, no more than one previous chemotherapy regimen for metastatic disease, and normal organ function were eligible, and patients with central nervous system involvement, P450-inducing or P450-suppressing drugs, or hypertriglyceridemia were excluded.


RESULTS
Thirty-three patients (21 males) were treated, 21 of whom had been treated previously with chemotherapy and/or biologic agents for advanced-stage disease. One patient had a partial response lasting 2 months. The median time to disease progression and overall survival were 10 weeks and 5 months, respectively. Toxicity was mild and predominantly mucocutaneous (stomatitis, diarrhea, and rash). Hyperlipidemia was cumulative and was managed with lipid-lowering agents.


CONCLUSIONS
CCI-779 was not sufficiently active in melanoma to warrant further testing as a single agent.
Margolin
Kim
K
Division of Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, California 91010, USA. kmargolin@coh.org
Longmate
Jeffrey
J
Baratta
Tracey
T
Synold
Tim
T
Christensen
Scott
S
Weber
Jeffrey
J
Gajewski
Thomas
T
Quirt
Ian
I
Doroshow
James H
JH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; C401859:temsirolimus; D020123:Sirolimus