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 (> or = 1.5 x 10(9)/l) and platelets (> or = 50 x 10(9)/l) or for a maximum of 28 days at a dosage of 0.3 microgram/kg/day (n = 7), 1 microgram/kg/day (n = 6) or 3 micrograms/kg/day (n = 7). Two of the initial 4 patients given rhIL-6 at 0.3 mu/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 micrograms/kg dose. At the 0.3 and 1 microgram/kg/day doses, 8 of 13 patients completed the study vs. only 2 of 7 at the 3 micrograms/kg/day dose. During rhIL-6 treatment, neutrophil recovery (> or = 500 x 10(6)/l) occurred in 12 patients and platelet recovery (> or = 20 x 10(9)/l) occurred in 6 patients, 5 of whom received the 0.3 or 1 microgram/kg/day s.c. dose. The maximal tolerated dose of rhIL-6 after autologous BMT appeared to be 1 microgram/kg/day s.c., a dose appreciably lower than the maximal tolerated dose after conventional cytotoxic therapy.
Lazarus
H M
HM
Department of Medicine, Ireland Cancer Center of University Hospitals of Cleveland, Case Western Reserve University, OH 44106, USA.
Winton
E F
EF
Williams
S F
SF
Grinblatt
D
D
Campion
M
M
Cooper
B W
BW
Gunn
H
H
Manfreda
S
S
Isaacs
R E
RE
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D015850:Interleukin-6 / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D015993:Life Tables; D008875:Middle Aged; D009504:Neutrophils; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome
D016298:Hematopoietic Cell Growth Factors; D015850:Interleukin-6; D011994:Recombinant Proteins