The pharmacologic basis of high dose chemotherapy with haematopoietic stem cell support for solid tumours

The theoretical basis of high dose chemotherapy with haematopoietic stem cell support (HDT) for solid tumours is the presumption of a linear, steep dose-response relationship for chemotherapy conditioning agents. We review preclinical pharmacologic studies evaluating steep dose-response relationships for different chemotherapeutic agents, identified through a MED-LINE and CANCER-LIT search of the English medical literature from January 1966 to December 1999. Only BCNU, melphalan, nitrogen mustard, and the combination of thiotepa and cyclophosphamide demonstrated steep dose-response relationships over a wide dose-range. The pharmacologic evidence for the use of other antineoplastic agents for HDT in solid tumours is non-existent. More preclinical studies are needed for a rational development of this therapeutic approach for solid tumours.