nartograstim and Leukopenia

A phase I study was conducted in patients with stage IIIB or IV non-small cell lung cancer to determine the maximum tolerated dose (MTD) of irinotecan combined with a fixed schedule of docetaxel and carboplatin with recombinant human granulocyte colony stimulating factor (rhG-CSF) (nartograstim) support. Docetaxel was given at 60 mg/m2 on day 1 with carboplatin. The dose of carboplatin was calculated using the Calvert formula to achieve an estimated AUC of 5.0 mg/ml x min. Irinotecan was administered at a starting dose of 40 mg/m2 on day 1 and increased in increments of 10 mg/m2. rhG-CSF was given at 1 microg/kg on days 5-15. Cycles were repeated every 3 weeks. Between February 1998 and March 1999, 22 patients were enrolled in this phase I study. Five patients were chemotherapy naive. The MTD of irinotecan was 60 mg/m2. Diarrhea was considered to be the dose-limiting toxicity. The irinotecan dose intensity of 16.7 mg/m2/week was low compared with other irinotecan-containing regimens. The overall response rate was 38.1% and median survival was 278 days. Irinotecan 50 mg/m2 in combination with 60 mg/m2 docetaxel and carboplatin on day 1 with rhG-CSF support is recommended for phase II study. The response rate and survival data in this phase I study are encouraging.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carboplatin; Carcinoma, Non-Small-Cell Lung; Docetaxel; Dose-Response Relationship, Drug; Female; Granulocyte Colony-Stimulating Factor; Humans; Irinotecan; Leukopenia; Lung Neoplasms; Male; Middle Aged; Paclitaxel; Taxoids

The present study was designed to evaluate the effects of a recombinant human G-CSF (rhG-CSF) and a mutein G-CSF (KW-2228) on leucopenia and tumor growth in mice treated with 5-fluorouracil (5-FU). In normal mice, the number of leucocytes (white blood cell, WBC) reached the peak 12 hours after a single injection of either type of G-CSF and decreased to the normal level after 24 hours. Daily administration induced a continuous increase in the WBC count, however, administrations at intervals did not. Meth-A fibrosarcoma was subcutaneously inoculated into the backs of syngeneic BALB/c mice. The mice were treated with 5-FU alone or with G-CSFs. Chemotherapy with 5-FU alone resulted in leucopenia and an insignificant inhibition of tumor growth. The conjunctive administration of G-CSFs with 5-FU resulted in a significantly augmented inhibition of tumour growth, and leukopenia was not seen. This augmenting effect was more prominent with KW-2228. These results suggest that in 5-FU chemotherapy G-CSFs may be beneficial in restoring the number of leucocytes from leucopenic state and in augmenting the tumor inhibitory effect. Furthermore, KW-2228 may be more beneficial than the natural type rhG-CSF.

Topics: Amino Acid Sequence; Animals; Combined Modality Therapy; Drug Synergism; Fibrosarcoma; Fluorouracil; Granulocyte Colony-Stimulating Factor; Immunologic Factors; Leukocyte Count; Leukopenia; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Protein Engineering; Recombinant Proteins