Prophylactic G-CSF and antibiotics enable a significant dose-escalation of triplet-chemotherapy in non-small cell lung cancer

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• 作者：J.N.H. Timmer-Bonte ; C.J.A. Punt ; H.F.M. vd Heijden ; C.E. van Die ; J. Bussink ; J.H. Beijnen ; A.D.R. Huitema ; V.C.G. Tjan-Heijnen
• 关键词：Dose-finding study ; G-CSF ; Antibiotics ; Prophylaxis ; NSCLC ; Chemotherapy-combinations ; Paclitaxel ; Cisplatin ; Teniposide ; Etoposide
• 刊名：Lung Cancer
• 出版年：2008
• 期刊代码：187_01695002
• 类别：med
• 出版时间：May 2008
• 卷：60
• 期：2
• 页码：222-230
• 文件大小：281 K

摘要

In advanced non-small cell lung cancer (NSCLC) the clinical benefit of a platinum-based doublet is only modest, therefore, attenuated dosed three-drug combinations are investigated. We hypothesized that with adequate support a full dosed chemotherapy triplet is feasible. The study was designed as a dose finding study of paclitaxel in chemotherapy-naive patients. Paclitaxel was given as a 3-h infusion on day 1, followed by fixed doses of teniposide (or etoposide) 100 mg/m² days 1, 3, 5 and cisplatin 80 mg/m² day 1 every 3 weeks. As myelotoxicity was expected to be the dose-limiting toxicity, prophylactic G-CSF and antibiotic support was evaluated. Indeed, paclitaxel 120 mg/m² resulted in dose-limiting neutropenia, despite G-CSF support. Teniposide/etoposide day 1, 3, 5 was less myelotoxic compared to day 1, 2, 3. G-CSF support allowed paclitaxel dose-escalation to 250 mg/m². The addition of prophylactic antibiotics enabled dose-escalation to 275 mg/m² without reaching MTD. In conclusion, G-CSF and antibiotics prophylaxis enables the delivery of a full dosed chemotherapy triplet in previously untreated NSCLC patients.