Isaacs, C., Robert, N.J., Bailey, F.A., Schuster, M.W., Overmoyer, B., Graham, M., . . . Kaye, J.A. (1997). Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. Journal of Clinical Oncology, 15, 3368–3377.

Intervention Characteristics/Basic Study Process

Patients were assigned randomly to receive either placebo or interleukin-11 (IL-11) 50 mcg/kg/day subcutaneous (SC). The study drug was blinded. Randomization was stratified by investigative site and also by whether patients had received any prior chemotherapy. SC administration began on day two and was given for a minimum of 10 days after the first cycle of chemotherapy.

Sample Characteristics

  • N = 77     
  • AGE: Older than 18 years of age
  • WOMEN: 100%
  • KEY DISEASE CHARACTERISTICS: Stage 2, 3, or 4 breast cancer and Eastern Cooperative Oncology Group (ECOG) status of 0–2
  • OTHER KEY SAMPLE CHARACTERISTICS: Patients treated with cyclophosphamide (3200 mg/m2) and doxorubicin (75 mg/m2) IV on same day; chemotherapy repeated every 21–28 days

Study Design

  • Randomized, blind study

Measurement Instruments/Methods

  • The primary endpoint was whether a patient required platelet transfusions during two cycles of chemotherapy.
  • Time to platelet recovery, open-label treatment, tumor response, time to neutrophil recovery, antibody development, safety, and efficacy








 

Results

Sixty-seven patients were assessable. Sixty-eight percent of patients in the IL-11 group did not receive transfusions, versus 41% in the placebo group (p = .04). The IL-11 group had a decreased total number of platelet transfusions (p = .03) and time to platelet recovery to greater than 50K in the second cycle (p = .01). Side effects in the IL-11 group (p < .05) were peripheral edema (68%), dyspnea (48%), pleural effusion (18%), and conjunctival infection (25%).

Limitations

  • All female patients
  • Only high-risk and advanced
  • Well-controlled
  • Did not demonstrate for dose intensity, maintenance of planned schedules
  • Open-label so everyone could crossover
  • Did not address how people stayed on track for schedule
  • IL-11 for first two cycles
  • How many women went on to get planned schedules?
  • Where was the science in 1997?