Phase I multicenter trial of interleukin 6 therapy after autologous bone marrow transplantation in advanced breast cancer

Our purpose was to determine the maximum tolerated dosage of rhIL-6 after high-dose cytotoxic chemotherapy and autologous BMT in patients with advanced breast cancer. Twenty patients (median age 43.5 years) received either CY and thiotepa (n=3) or CY, thiotepa and carboplatin (n=17) for 4 days. Unpurged autologous BM was reinfused 72 h later. Daily rhIL-6 therapy began the day of marrow infusion and continued until recovery of neutrophils (≥1.5 x 10⁹/l) and platelets (≥50 x 10⁹/l) or for a maximum of 28 days at a dosage of 0.3 μg/kg/day (n=7), 1 μg/kg/day (n=6) or 3 μg/kg/day (n=7). Two of the initial 4 patients given rhIL-6 at 0.3 μg/kg i.v. experienced grade 4 hyperbilirubinemia, so subsequent patients received s.c. rhIL-6. Most toxicities attributable to rhIL-6 were reversible or mild constitutional symptoms, but dose-limiting grade 4 hyperbilirubinemia also occurred in 3 of the 7 patients receiving the 3 μg/kg dose. At the 0.3 and 1 μg/kg/day doses, 8 of 13 patients completed the study vs, only 2 of 7 at the 3 μg/kg/day dose. During rhIL-6 treatment, neutrophil recovery (≥500 x 10⁶/l) occurred in 12 patients and platelet recovery (≥20 x 10⁹/l) occurred in 6 patients, 5 of whom received the 0.3 or 1 μg/kg/day s.c. dose. The maximal tolerated dose of rhIL-6 after autologous BMT appeared to be 1 μg/kg/day s.c., a dose appreciably lower than the maximal tolerated dose after conventional cytotoxic therapy.