High-Dose Combination Alkylating Agent Therapy With Autologous Bone Marrow Rescue for Refractory Solid Tumors

Twenty-six adults, ages 27 to 60, with refractory met-astatic solid tumors were treated with high-dose cy-clophosphamide (Cy) + carmustine (BCNU) at one of three escalating dose schedules followed by autolo-gous bone marrow transplantation (ABMT). Toxicity was severe and dose-related, with the maximum tol-erated dose for the combination determined to be Cy 160 mg/kg and BCNU 900 mg/m 2. Median time to WBC recovery (! 1,000//L) was 13 days post-ABMT (range, nine to 22 days) and to a platelet count of- 50,000/OpL, 22 days (range, 13 to 83 days). Sixteen of 20 evaluable patients (80%) responded to therapy with at least 50 % reduction in measurable tumor, T HE COMMON nonhematologic neoplasms in adults are rarely curable with standard dose cytotoxic chemotherapy. In fact, with the possible exception of small-cell lung carcinoma and breast cancer, meaningful extension of sur-vival is unlikely once metastases are clinically apparent. Possible reasons for treatment failure include both intrinsic tumor cell drug resistance and dose-limiting drug toxicities. Until new and more effective agents are introduced, attention must be directed at maximizing the efficacy of available drugs and, when possible, circumvent-ing dose-limiting side effects. Experimental evidence, reviewed by Frei et al, ' supports a dose-response relationship for most antitumor agents against many tumor types. Preliminary clinical studies designed to explore the dose-responsiveness of human malignancies to cytotoxic drugs have been initiated at several centers. These investigations have been aided by the development of techniques for harvesting an