Phase I study of interleukin-6 in children with solid tumours in relapse

Eur J Cancer. 1997 Sep;33(10):1620-6. doi: 10.1016/s0959-8049(97)00181-0.

Abstract

The aim of this study was to evaluate the feasibility, toxicity and efficacy of escalating doses of subcutaneous recombinant interleukin-6 (IL-6) in children with solid tumours in relapse. Recombinant IL-6 was administered subcutaneously once daily for 14 consecutive days, with a 14 day follow-up period. The starting dose for IL-6 was 1 microgram/kg/day and was escalated in subsequent patients groups until 10 micrograms/kg. Doses were escalated every 3 patients, provided that grade III or IV organ toxicity did not occur at the preceding dose level. Twelve patients were treated, three at each dose level. No grade 3-4 major organ toxicity was observed. Flu-like symptoms and fatigue were the most common side effects. All these symptoms resolved after the end of IL-6 administration. Significant increases in acute-phase proteins (CRP [C reactive protein], fibrinogen) and ESR (Erthrocyte sedimentation rate) were observed in all patients. Stimulatory effects on thrombocytopoiesis were observed at every dose level, and were maximal at 5 micrograms/kg and 10 microgram/kg. There was no tumour response observed during IL-6 administration. Pharmacokinetic profiles performed in 3 patients are consistent with previous reports in adults. IL-6 is a promising new cytokine for paediatric oncology, in particular to increase thrombocyte counts. We recommend that further studies in children proceed at a dose of 5-10 micrograms/kg/day in a once or, better, twice daily administration.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Adolescent
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Immunologic
  • Feasibility Studies
  • Female
  • Humans
  • Interleukin-6 / adverse effects
  • Interleukin-6 / blood
  • Interleukin-6 / therapeutic use*
  • Male
  • Neoplasms / blood
  • Neoplasms / therapy*
  • Platelet Count / drug effects
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / blood
  • Recombinant Proteins / therapeutic use

Substances

  • Acute-Phase Proteins
  • Interleukin-6
  • Recombinant Proteins