Pulmonary toxicity of induction chemotherapy prior to standard or high-dose chemotherapy with autologous hematopoietic support

We closely followed the pulmonary function of 150 consecutive high-risk bre ast cancer patients who underwent standard induction CAF (cyclophosphamide, doxorubicin, 5-fluorouracil) chemotherapy, followed by randomization to ei ther standard-dose CPB (cyclophosphamide, cisplatin, bischloroethylnitrosou rea [BCNU]) chemotherapy (SDC) or to high-dose CPB chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) and peripheral blood progenit or cell support (PBPCS). Previously, we have described a delayed pulmonary toxicity syndrome (DPTS) which characterizes the pulmonary dysfunction afte r HDC and ABMT in this patient population. However, little is known concern ing the role induction chemotherapy plays in its development. We found that after three cycles of induction CAF, the mean diffusing capacity of the lu ngs for carbon monoxide (DLCO) significantly decreased by 12.6%. Additional ly, in patients receiving HDC, the mean DLCO further decreased to a nadir o f 55.2 +/- 14.1% which was significantly lower than those receiving SDC (na dir: 80.7 +/- 12.3%). DPTS occurred in 72% of patients receiving HDC as com pared with only 4% of patients receiving SDC. All individuals diagnosed wit h DPTS were treated with prednisone and the 2-yr follow-up of pulmonary fun ction revealed a gradual improvement in mean DLCO such that there were no d ifferences between HDC and SDC groups at the end of the study. No mortality was attributable to pulmonary toxicity in either group. After induction ch emotherapy, but before HDC, bronchoalveolar lavage (BAL) demonstrated signi ficant elevations in interleukin-6 (IL-6), IL-8, neutrophils, and lymphocyt es. We conclude that induction CAF produces asymptomatic pulmonary dysfunct ion and inflammation which may prime the lungs for further injury by HDC an d predispose to the development of DPTS. Fortunately, in this specific ABMT patient population, the early and judicious use of prednisone appears to i mprove pulmonary function in patients who develop DPTS.