Temozolomide plus thalidomide in patients with advanced melanoma: results of a dose-finding trial.
OBJECTIVE
To establish a safe and tolerated regimen of an oral cytotoxic agent, temozolomide, and a cytostatic agent, thalidomide, in patients with unresectable stage III or IV malignant melanoma.


METHODS
Patients with unresectable stage III or IV melanoma without brain metastases were entered successively onto four treatment cohorts: level 1, temozolomide 50 mg/m(2)/d for 6 weeks followed by a 4-week break; levels 2, 3, and 4, temozolomide 75 mg/m(2)/d for 6 weeks followed, respectively, by breaks of 4, 3, and 2 weeks. Thalidomide was started at 200 mg/d, and escalated to a maximum dose of 400 mg/d. Safety was assessed at weeks 2 and 4 and every 4 weeks thereafter; tumor response was evaluated every 8 to 10 weeks.


RESULTS
Twelve patients were enrolled, three on each cohort. Therapy was generally well tolerated on all of the treatment schedules. Thalidomide at a dose of 400 mg/d was well tolerated in patients younger than 70, and 200 mg/d was well tolerated in older patients. The most common adverse events were grade 2 or 3 constipation and neuropathy, which were attributed to thalidomide. Five major responses (one complete, four partial) were documented, all at dose levels 2 to 4. Three of the five responding patients were in the over-70 age group. The median duration of response was 6 months (range, 4 to 17+ months), and the median overall survival was 12.3 months (range, 4 to 19+ months).


CONCLUSIONS
The combination of temozolomide and thalidomide was well tolerated and had antitumor activity in patients with advanced melanoma, including elderly patients over 70 years old.
Hwu
Wen-Jen
WJ
Departments of Medicine, Epidemiology and Biostatistics, and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. hwuw@mskcc.org
Krown
Susan E
SE
Panageas
Katherine S
KS
Menell
Jennifer H
JH
Chapman
Paul B
PB
Livingston
Philip O
PO
Williams
Linda J
LJ
Quinn
Carolyn J
CJ
Houghton
Alan N
AN
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D015996:Survival Rate; D000077204:Temozolomide; D013792:Thalidomide / Q000008:administration & dosage / Q000494:pharmacology
D013792:Thalidomide; D003606:Dacarbazine; D000077204:Temozolomide