Effects of interleukin-3 on myelosuppression induced by chemotherapy for ovarian cancer and small cell undifferentiated tumours.
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.
Dercksen
M W
MW
Department of Medical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam.
Hoekman
K
K
ten Bokkel Huinink
W W
WW
Rankin
E M
EM
Dubbelman
R
R
van Tinteren
H
H
Wagstaff
J
J
Pinedo
H M
HM
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007377:Interleukin-3 / Q000009:adverse effects / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use
D015703:Antigens, CD; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D007377:Interleukin-3; D011994:Recombinant Proteins