Bone marrow autotransplantation for solid tumors--prospects

Autologous bone marrow transplantation (AuBMT) is in clinical trial for patients with metastatic solid tumors, particularly breast cancer. This review deals with the potential of this approach. AuBMT is curative for the leukemias and lymphomas. Curative cancer chemotherapy has, almost without exception, required combinations of agents wherein dose was well maintained. However, curative chemotherapy strategies for the hematologic neoplasms have not proven successful for the common solid tumors. An important exception is that standard adjuvant chemotherapy can "cure" some micrometastatic tumors. Preclinical studies indicate the effectiveness of alkylating agents in terms of maintained dose effect through multiple logs of tumor cell kill; difficulty in developing drug resistance; general lack of cross resistance; and synergy for alkylating agents used in combination. There is an increasingly effective experimental basis for the construct of intensification regimens employing combinations of alkylating agents. Differing nonmyelosuppressive toxicity for alkylating agents provides a basis for maintaining dose when employed in combination in the autologous marrow situation. The aforementioned studies and cytokinetic analyses of combined intensive alkylating agent therapy for breast cancer support the potential of this approach. Clinical trials indicate a high response rate in refractory breast cancer. Trials involving induction chemotherapy followed by combined alkylating agent intensification have produced substantial complete remission rates. The duration of response has, in most studies, been short. This approach is associated with major toxicity, including mortality, and is expensive. Experimental and preliminary clinical evidence as marshalled in this review indicate that this is a promising area for therapeutic research.