High-dose chemotherapy with the alkylating agent combination CTC appears to add significantly to the efficacy of conventional dose chemotherapy in patients with high-risk breast cancer, provided that the HER-2/neu gene is not amplified in the tumor. As a high-dose chemotherapy regimen, CTC is associated with significant toxicity \[31,32\]. Although high-dose alkylating therapy seems to be effective, there is virtually nothing known about the dose-response curve for this combination (for a detailed discussion see the classical paper by E. Frei III \[32\]. If one assumes that the efficacy increase levels off with increasing dose, the efficacy of tCTC might be almost as great as that of CTC, but with considerably less toxicity. In addition, two closely spaced courses of tCTC might further increase the efficacy of the regimen. There are some suggestions that a double transplant may be more effective than a single one, in multiple myeloma and in Ewing sarcoma. A similar suggestion has also been made for breast cancer (study of Nitz et al ref 4, table 1).