THE IMPACT OF CONVENTIONAL PLUS HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION ON HEMATOLOGIC TOXICITY DURING SUBSEQUENT LOCAL-REGIONAL RADIOTHERAPY FOR BREAST-CANCER

Background. Forty patients with Stage II-III breast cancer with 10 or more positive axillary nodes were treated with mastectomy followed by four cycles of standard dose CAF (cytoxan, Adriamycin, 5-FU), followed by high dose cytoxan, cisplatin, carmustine (HDCT) with autologous bo ne marrow transplant support (ABMT), and local-regional radiotherapy ( LR XRT). During LR XRT, the hematologic toxicity experienced by these patients appeared more severe than that usually seen in patients not h eavily pretreated with chemotherapy. Radiation therapy was interrupted in four patients (10%) because of thrombocytopenia and leukopenia. Th is observation prompted a comparison of the hematologic changes seen i n this group with those seen in patients not treated previously with c hemotherapy. Methods. A detailed analysis of changes in hematologic pa rameters during LR XRT was performed in 33 evaluable patients who rece ived CAF-HDCT/ABMT and compared with a ''control'' group of 17 women w ho did not receive prior chemotherapy. Results. The mean pretreatment leukocyte, platelet, and hematocrit counts were lower in the CAF-HDCT/ ABMT group than in the control group, with the differences indicating statistical significance for the latter two (P = 0.17, P < 0.001, and P = 0.001, respectively). None of the control patients required a tre atment interruption because of hematologic toxicity, whereas four of t he CAF-HDCT/ABMT patients did. Among the CAF-HDCT/ABMT patients, a leu kocyte count nadir of less than 2.0, a platelet nadir of less than 50, 000, and a hematocrit nadir of less than 25 occurred in 12%, 19%, and 9%, respectively. The corresponding rates of control patients were 6%, 0%, and 0%, respectively. Relative to their pretreatment levels, howe ver, both groups experienced similar declines in platelet and leukocyt e counts. Conclusion. The higher rate of hematologic toxicity observed in the patients who previously received conventional chemotherapy plu s HDCT/ABMT appears to have been due primarily to lower preradiotherap y blood counts.