Temozolomide plus thalidomide in patients with brain metastases from melanoma: a phase II study.
BACKGROUND
Temozolomide plus thalidomide is a promising oral combination regimen for the treatment of metastatic melanoma. The current Phase II study examined the efficacy and safety of this combination in chemotherapy-naive patients with brain metastases.


METHODS
Patients with histologically confirmed metastatic melanoma and measurable brain metastases received temozolomide (75 mg/m2 per day for 6 weeks with a 2-week break between cycles) plus concomitant thalidomide (200 mg/day escalating to 400 mg/day for patients < 70 years or 100 mg/day escalating to 250 mg/day for patients > or = 70 years). The primary end point was tumor response in the brain assessed every 8 weeks.


RESULTS
Twenty-six patients with a median age of 60 years were treated. All patients had progressive brain metastases: 16 were symptomatic and 25 had extensive extracranial metastases. Eight patients had received whole-brain radiotherapy, 4 had received stereotactic radiotherapy, and 8 had received craniotomy with resection of hemorrhagic lesions. Fifteen patients completed > or = 1 cycle (median, 1 cycle; range, 0-4 cycles), and 11 discontinued treatment before completing 1 cycle (7 for intracranial hemorrhage, 2 for pulmonary embolism, 1 for deep vein thrombosis, and 1 for Grade 3 rash). Of 15 patients assessable for response, 3 had a complete or partial response (12% intent to treat) and 7 had minor response or stable disease in the brain. However, 5 of these 10 patients had disease progression at extracranial sites. The median survival period was 5 months for all 26 patients and 6 months for the 15 assessable patients.


CONCLUSIONS
Temozolomide plus thalidomide was an active oral regimen for patients with brain metastases from malignant melanoma.
Hwu
Wen-Jen
WJ
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. wenjhwu@mdanderson.org
Lis
Eric
E
Menell
Jennifer H
JH
Panageas
Katherine S
KS
Lamb
Lynne A
LA
Merrell
Janene
J
Williams
Linda J
LJ
Krown
Susan E
SE
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 / Q000188:drug therapy* / Q000556:secondary; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D000077204:Temozolomide; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
D013792:Thalidomide; D003606:Dacarbazine; D000077204:Temozolomide