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Our objective was to evaluate the toxicity and antitumor efficacy of concurrent biochemotherapy in metastatic melanoma patients and the effectiveness of adding temozolomide to protect the brain from metastases. Twenty-three patients with advanced inoperable melanoma were hospitalized for 5-6 days for the following treatment: cisplatin 20 mg/m daily for 4 days, vinblastine 1.6 mg/m daily for 4 days and oral temozolomide 250 mg/m daily for 5 days, with 18 x 10 IU/m intravenous interleukin-2 by continuous infusion for 4 days (the dose was cut daily by 50%) and 5 x 10 U/m interferon-alfa subcutaneously daily for 5 days, repeated at 28-day intervals for a maximum of nine courses. According to the standard World Health Organization response criterion, the objective response rate was 43.4% and the median survival was 18.6 months. All but one patient survived for more than 12 months, and no responding patient progressed first in the brain. Substituting dacarbazine by temozolomide in the MD Anderson melanoma section protocol appears to offer protection against dissemination of brain metastases, equal activity in the periphery and a possible lower incidence of toxicity due to the oral route.

Background: The precise genes involved in conferring prostate cancer risk in sporadic and familial cases are not fully known., Objectives: To evaluate the genetic profile within several candidate genes of unselected prostate cancer cases and to correlate this profile with disease parameters., Methods: Jewish Israeli prostate cancer patients (n = 224) were genotyped for polymorphisms within candidate genes: p53, ER, VDR, GSTT1, CYP1A1, GSTP1, GSTM1, EPHX and HPC2/ELAC2, followed by analysis of the genotype with relevant clinical and pathologic parameters., Results: The EPHX gene His113 allele was detected in 21.4% (33/154) of patients in whom disease was diagnosed above 61 years, compared with 5.7% (4/70) in earlier onset disease (P < 0.001). Within the group of late-onset disease, the same allele was noted in 5.5% (2/36) with grade I tumors compared with 18% (34/188) with grade II and up (P = 0.004). All other tested polymorphisms were not associated with a distinct clinical or pathologic feature in a statistically significant manner., Conclusions: In Israeli prostate cancer patients, the EPHX His113 allele is seemingly associated with a more advanced, late-onset disease. These preliminary data need to be confirmed by a larger and more ethnically diverse study.