THE TOXICITY OF RADIOTHERAPY FOLLOWING HIGH-DOSE CHEMOTHERAPY WITH PERIPHERAL-BLOOD STEM-CELL SUPPORT IN HIGH-RISK BREAST-CANCER - A PRELIMINARY-ANALYSIS

High-dose chemotherapy with autologous bone marrow and/or peripheral b lood stem cell (PBSC) support is increasingly employed in the adjuvant treatment of high-risk breast cancer. Subsequent radiotherapy has bee n reported to be associated with morbidity and mortality resulting fro m pulmonary toxicity. In addition, the course of radiation therapy may be hampered by excess myelosuppression. The aim of this study was to investigate the contribution to radiation-induced toxicity of a high-d ose chemotherapy regimen (CTC) that incorporates cyclophosphamide, thi otepa and carboplatin, in patients with high-risk breast cancer. In tw o randomised single institution studies, 70 consecutive patients recei ved anthracycline-containing adjuvant chemotherapy (FEC: 5-fluorouraci l, epirubicin and cyclophosphamide) followed by radiotherapy to achiev e maximal local control. Of these patients, 34 received high-dose CTC with autologous PBSC support. All patients tolerated the full radiatio n dose in the planned time schedule. Radiation pneumonitis was observe d in 5 patients (7%), 4 of whom had undergone high-dose chemotherapy ( P = 0.38). All 5 responded favourably to prednisone. Fatal toxicities were not observed. Myelosuppression did not require interruption or un timely discontinuation of the radiotherapy, although significant reduc tions in median nadir platelet counts and haemoglobin levels were obse rved in patients who had received high-dose chemotherapy (P = 0.0001). The median nadir of WBC counts was mildly but significantly decreased during radiotherapy (P = 0.01). Red blood cell or platelet transfusio ns were rarely indicated. Adequate radiotherapy for breast cancer can be safely administered after high-dose CTC with autologous PBSC suppor t. Radiation-induced myelotoxicity is clearly enhanced following CTC, but this is of little clinical significance. Radiation pneumonitis aft er high-dose therapy may occur more often in patients with a history o f lung disease or after a relatively high radiation dose to the chest wall. Other high-dose regimens, particularly those incorporating drugs with known pulmonary toxicity (such as BCNU), may predispose patients to radiation pneumonitis. Copyright (C) 1996 Published by Elsevier Sc ience Ltd