This invention relates to compositions comprising temozolomide and thalidomide which can be used in the treatment or prevention of cancer, in particular malignant melanoma, cancer of the skin, subcutaneous tissue, lymph nodes, brain, lung, liver, bone, intestine, colon, heart, pancreas, adrenals, kidney, prostate, breast, colorectal, or a combination thereof. A particular composition comprises temozolomide, or a pharmaceutically acceptable salt, solvate, or clathrate thereof, and thalidomide, or a pharmaceutically acceptable salt, solvate, or clathrate thereof. The invention also relates to methods of treating or preventing cancer, in particular malignant melanoma, cancer of the skin, subcutaneous tissue, lymph nodes, brain, lung, liver, bone, intestine, colon, heart, pancreas, adrenals, kidney, prostate, breast, colorectal, or a combination thereof, which comprise the administration of temozolomide and thalidomide and another anti-cancer drug to a patient in need of such treatment or prevention. The invention further relates to methods of reducing or avoiding adverse side effects associated with the administration of cancer chemotherapy or radiation therapy which comprise the administration of temozolomide and thalidomide to a patient in need of such reduction or avoidance.