Emergence of progressive or recurrent disease is a consequence of selection and overgrowth of pre-existent, drug resistant cells during treatment. Based on the mechanism of somatic cell mutation, Goldie and Coldman (5,6) proposed a model for the emergence of drug resistant cells in tumors. Their model proposed that alternating non-cross-resistant combinations would prevent the overgrowth of resistant cancer cells and improve the probability of tumor control or cure. Their recommendation assumed that the two non-cross-resistant regimens were of equal or similar efficacy and that the drugs contained in the two combinations could not be administered together in one single regimen.