A perspective on dose-intensive therapy with autologous bone marrow transplantation for solid tumors

The poor results seen in patients with advanced solid tumors treated with conventional-dose therapy have stimulated interest in alternative approaches, including higher than standard doses of chemotherapy. Most chemotherapeutic agents exhibit a steep dose-response curve in laboratory models that is log linear in nature. Autologous bone marrow transplantation applies this concept by employing dose-intensive therapy with chemotherapeutic agents whose dose-limiting toxicity is myelosuppression. Alkylating agents are logical choices for high-dose chemotherapy because they have a steep dose-response curve both in vitro and in vivo, and this response is maintained through multiple logs of tumor cell kill. Although at conventional doses myelosuppression is dose-limiting, at transplant doses each agent has its particular dose-limiting organ toxicity which allows alkylating agents to be employed in combination.