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 af ter high-dose cytotoxic chemotherapy and autologous BMT in patients wi th advanced breast cancer, Twenty patients (median age 43.5 years) rec eived either CY and thiotepa (n = 3) or CY, thiotepa and carboplatin ( n = 17) for 4 days. Unpurged autologous BM was reinfused 72 h later. D aily rhIL-6 therapy began the day of marrow infusion and continued unt il recovery of neutrophils (greater than or equal to 1.5 x 10(9)/l) an d platelets (greater than or equal to 50 x 10(9)/l) or for a maximum o f 28 days at a dosage of 0.3 mu g/kg/day (n = 7), 1 mu g/kg/day (n = 6 ) or 3 mu g/kg/day (n = 7). Two of the initial 4 patients given rhlL-6 at 0.3 mu/kg i.v. experienced grade 4 hyperbilirubinemia, so subseque nt 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 receiv ing the 3 mu g/kg dose. At the 0.3 and 1 mu g/kg/day doses, 8 of 13 pa tients completed the study vs. only 2 of 7 at the 3 mu g/kg/day dose. During rhIL-6 treatment, neutrophil recovery (greater than or equal to 500 x 10(6)/l) occurred in 12 patients and platelet recovery (greater than or equal to 20 x 10(9)/l) occurred in 6 patients, 5 of whom rece ived the 0.3 or 1 mu g/kg/day s.c. dose. The maximal tolerated dose of rhIL-6 after autologous BMT appeared to be 1 mu g/kg/day s.c., a dose appreciably lower than the maximal tolerated dose after conventional cytotoxic therapy.