Conventional stroke risks are thought responsible for most cerebral ischemic events (CIE) in adult cancer patients. Also suspected as a risk is cisplatin chemotherapy, alone or in combination with tumor angiogenesis inhibitor. We investigated whether treatment or tumor characteristics, independently of conventional stroke risks, are associated with CIE in a retrospective cohort study of 1,559 patients with advanced non-small cell lung cancer or hormone-refractory prostate cancer followed during 3 clinical trials of matrix metalloprotease inhibitor (prinomastat) versus placebo, with chemotherapy (gemcitabine/cisplatin, paclitaxel/carboplatin or mitoxantrone/prednisone). During 11,907 patient-months, 28 CIE (17 cerebral infarction, 11 transient ischemic attack) were diagnosed in 24 patients, all but 1 over 55 years. Neither prinomastat, platinum-based chemotherapy nor their combination was associated with CIE after age 55. However, such events were predicted by the presence of distant metastases in the liver or lungs and not in distant lymph nodes (hazard estimate 4.6, 95% CI 2.0-10.5, adjusted for conventional stroke risks). Further studies are needed to verify this preliminary finding and determine its generalizability to advanced tumors other than lung or prostate cancer.