Cytotoxic drugs, hormones, antihormones, and biologic agents have become increasingly effective means of treating cancer. Many
patients are treated on protocols to provide optimal therapy for refractory or poorly responsive malignancies. Treatment may be
inadequate or ineffective because of drug resistance of the tumor cells. This has been attributed to spontaneous genetic mutations in
subpopulations of cancer cells prior to exposure to chemotherapy. After chemotherapy has eliminated the sensitive cells, the
resistant subpopulation grows to become the predominant cell type (Goldie-Coldman hypothesis). This has been the basis of
alternating non-cross-resistant chemotherapy regimens.