Temozolomide plus thalidomide in patients with brain metastases from melanoma

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 ≥ 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 ≥ 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. Cancer 2005. © 2005 American Cancer Society. In the current Phase II study examining the efficacy and safety of temozolomide plus thalidomide in chemotherapy‐naive patients with brain metastases, 3 patients had a complete or partial response (12% intent to treat), and 7 patients had a minor response or stable disease in the brain. However, 5 of these 10 patients had disease progression at extracranial sites. The current study suggested that temozolomide plus thalidomide is a promising oral regimen for brain metastases from malignant melanoma.