Phase II study of temozolomide plus thalidomide for the treatment of metastatic melanoma.
OBJECTIVE
To further investigate the efficacy and safety of temozolomide plus thalidomide in patients with metastatic melanoma without brain metastases.


METHODS
Patients with histologically confirmed advanced-stage metastatic melanoma were enrolled in an open-label, phase II study. The primary end point was response rate. Patients received temozolomide (75 mg/m2/d x 6 weeks with a 2-week rest between cycles) plus concomitant thalidomide (200 mg/d with dose escalation to 400 mg/d for patients < 70 years old, or 100 mg/d with dose escalation to 250 mg/d for patients >/= 70 years old). Treatment was continued until unacceptable toxicity or disease progression occurred.


RESULTS
Thirty-eight patients (median age, 62 years) with stage IV (three patients with M1a, eight with M1b, and 26 with M1c) or stage IIIc (one patient) melanoma and a median of four metastatic sites were enrolled, and received a median of two cycles of therapy. Twelve patients (32%) had an objective tumor response, including one with an ongoing complete response of 25+ months' duration and 11 with partial responses. Five patients achieving partial response with a more than 90% reduction of disease were converted to a complete response with surgery. Treatment was generally well tolerated. Median survival was 9.5 months (95% confidence interval, 6.05 to 19.38 months), with a median follow-up among survivors of 24.3 months.


CONCLUSIONS
The combination of temozolomide plus thalidomide seems to be a promising and well-tolerated oral regimen for metastatic melanoma that merits further study.
Hwu
Wen-Jen
WJ
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. hwuw@mskcc.org.
Krown
Susan E
SE
Menell
Jennifer H
JH
Panageas
Katherine S
KS
Merrell
Janene
J
Lamb
Lynne A
LA
Williams
Linda J
LJ
Quinn
Carolyn J
CJ
Foster
Theresa
T
Chapman
Paul B
PB
Livingston
Philip O
PO
Wolchok
Jedd D
JD
Houghton
Alan N
AN
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D016019:Survival Analysis; D000077204:Temozolomide; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
D013792:Thalidomide; D003606:Dacarbazine; D000077204:Temozolomide