Brain metastases (BM) are among the most devastating and debilitating complications of melanoma. This retrospective study was conducted to gain a better understanding of patient and disease characteristics that have the greatest impact on overall survival in melanoma patients with BM; therapeutic interventions were also assessed. The records of all patients diagnosed with cutaneous melanoma and BM who were seen at Memorial Sloan-Kettering Cancer Center between 1991 and 2001 were retrospectively reviewed. A variety of factors, including age at diagnosis of stage IV disease, gender, race, disease stage at diagnosis, presence of BM at diagnosis of stage IV disease, neurologic symptoms, radiographic findings, number of BM, status and site(s) of extracranial metastasis, and treatment modalities, were analyzed for correlation with overall survival using univariate and multivariate Cox regression models. The records of 355 patients with BM were included in the analysis. On univariate analysis, seven patient and disease characteristics were significantly associated with poorer survival: age > 65 years, extracranial metastases, BM at stage IV diagnosis, neurologic symptoms, four or more BM, hydrocephalus, and leptomeningeal metastases. Of these, age, extracranial metastasis, neurologic symptoms, and number of BM were significantly associated with poorer survival in a multivariate analysis. Multivariate analysis of treatment modalities suggested that patients who had surgery, radiosurgery, or chemotherapy with temozolomide had improved survival outcomes, although this analysis has limitations. The prognostic factors identified in this retrospective study should be considered when making treatment decisions for patients with BM and used as stratification factors in future clinical trials.

The combination of temozolomide plus thalidomide seems to be a promising and well-tolerated oral regimen for metastatic melanoma that merits further study.

BACKGROUNDTemozolomide 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.METHODSPatients 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.RESULTSTwenty‐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.CONCLUSIONSTemozolomide plus thalidomide was an active oral regimen for patients with brain metastases from malignant melanoma. Cancer 2005. © 2005 American Cancer Society.

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