[Effect of recombinant human granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with lung cancer].
In an attempt to evaluate rG-CSF for preventing and reducing the period of chemotherapy-induced neutropenia, phase II studies of the agent, KRN 8601, have been conducted in patients receiving chemotherapy for lung cancer. In the cooperative study, 53 patients with lung cancer were fully evaluated. The chemotherapy regimen for the patients enrolled in the study was not specified, but an identical regimen with an identical dose and schedule was mandatory for the first cycle in which the patients did not receive the rG-CSF, and for the following cycles in which they received it after completion of chemotherapy for 14 days consecutively. Patients were allocated to receive the agents either at a dose of 100, 200 or 400 micrograms/m2 via intravenous drip infusion; or at as ub cutaneous dose of 25, 75, or 125 micrograms. In the author's study, all the 9 patients with non-small cell lung cancer received a 3-drug combination of vindesine, ifosfamide, and cisplatin(VIP) at an identical dose throughout the cycles. The rG-CSF was administered on the second and the following cycles at a dose of 100 micrograms/m2, subcutaneously, in the same manner as the above. Myelogram and neutrophil functions, i.e., superoxide anion production, chemotactic, and phagocytic activity, were serially determined in these patients. With intravenous dose of 100 micrograms/m2, the rG-CSF considerably elevated the nadir count of neutrophils and significantly reduced the duration of neutropenia. Subcutaneously administered rhG-CSF at 75 micrograms doses did as with intravenous infusion. The optimal dose of the agent in conventional chemotherapy was estimated to be 100 micrograms/m2 when infused intravenously, and 75-125 micrograms subcutaneously. Subcutaneously administered rG-CSF at a dose of 100 micrograms/m2 did not contribute to spare the nadir count of neutrophils, but contributed toward reducing the period of neutropenia induced by the 3-drug combination which was much more myelosuppressive than conventional regimens. Thus, the optimal dose of the agent should be determined according to the dose-intensity of chemotherapy. Peripheral neutrophils obtained after recovery from VIP-induced neutropenia showed a normal activity in superoxide anion production and mobility when combined with rG-CSF, although the activity showed a trend to remain subnormal in the recovered neutrophils without rG-CSF. In conclusion, rG-CSF considerably reduces the neutropenia and possibly reduces infections caused by intensive chemotherapy. Hereafter, clinical trials must determine whether rG-CSF improve the therapeutic outcomes of patients receiving chemotherapy in terms of response rate and patient survival.
Dept. of Medicine, Okayama University Medical School.
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Ohnoshi
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Ueoka
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Kodani
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Kamei
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Kimura
D000230:Adenocarcinoma / Q000188:drug therapy / Q000628:therapy; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000628:therapy; D002945:Cisplatin / Q000008:administration & dosage; D003115:Colony-Stimulating Factors / Q000627:therapeutic use*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000628:therapy; D011994:Recombinant Proteins / Q000627:therapeutic use*; D014751:Vindesine / Q000008:administration & dosage
D003115:Colony-Stimulating Factors; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D002945:Cisplatin; D014751:Vindesine; D007069:Ifosfamide