Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours

Br J Cancer. 1993 Nov;68(5):996-1003. doi: 10.1038/bjc.1993.468.

Abstract

Two clinical studies were undertaken to study the toxicity profile and effects of interleukin-3 (rhIL-3) on chemotherapy-induced myelosuppression. Fifteen patients with recurrent ovarian carcinoma were treated with high dose carboplatin (800 mg m-2). All patients received 5.0 micrograms/kg/d rhIL-3 subcutaneously but timing and duration of rhIL-3 treatment differed. Constitutional symptoms were the major toxicity and in addition to the carboplatin-induced nausea and vomiting the combination was poorly tolerated. In 5/15 patients receiving high dose carboplatin rhIL-3 administration was discontinued due to nephrotoxicity (2 x), hypotension, severe malaise and bone pain. In this study, rhIL-3 ameliorated chemotherapy-induced neutropenia as well as thrombocytopenia and reduced the requirement for platelet transfusions in the second cycle of chemotherapy. However, rhIL-3 failed to prevent cumulative platelet toxicity. In the second study 12 patients with small cell undifferentiated cancers were treated with carboplatin, etoposide and ifosfamide. Three dose levels of rhIL-3 were explored (0.125, 5.0 and 7.5 micrograms/kg/d). In this study, toxicity of the treatment was mild, however, no beneficial haematologic effects of rhIL-3 could be demonstrated. In conclusion, the haematological effects of rhIL-3 were modest and dependent on the chemotherapeutic regimen, timing and duration of rhIL-3 treatment (in relation to the expected nadir). In general rhIL-3-induced toxicity was mild, but combination with high dose carboplatin could be hazardous if rhIL-3 is initiated at 24 h after the cytostatic agent.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / analysis
  • Antigens, CD34
  • Antineoplastic Agents / adverse effects*
  • Bone Marrow / drug effects*
  • Carcinoma, Small Cell / drug therapy*
  • Female
  • Humans
  • Interleukin-3 / adverse effects
  • Interleukin-3 / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Middle Aged
  • Neutrophils / drug effects
  • Ovarian Neoplasms / drug therapy*
  • Platelet Count / drug effects
  • Recombinant Proteins / therapeutic use

Substances

  • Antigens, CD
  • Antigens, CD34
  • Antineoplastic Agents
  • Interleukin-3
  • Recombinant Proteins