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.
Ayash
L J
LJ
Dana-Farber Cancer Institute.
Antman
K
K
Cheson
B D
BD
D000477:Alkylating Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D016026:Bone Marrow Transplantation / Q000379:methods; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000601:surgery*
D000477:Alkylating Agents; D000970:Antineoplastic Agents