Annals of Oncology Advance Access originally published online on May 2, 2006
Annals of Oncology 2006 17(7):1128-1133; doi:10.1093/annonc/mdl084
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© 2006 European Society for Medical Oncology
A multicentre randomised phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer
1 Cancer Therapeutics Research Group, Department of Haematology-Oncology; 2 Department of Pharmacology, National University Hospital, Singapore; 3 Cancer Therapeutics Research Group, Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; 4 Clinical Trials & Epidemiology Research Unit, Ministry of Health, Singapore
* Correspondence to: Dr B. C. Goh, Department of Haematology-Oncology, 5 Lower Kent Ridge Road, National University Hospital, Singapore, 119074. Tel: +65 6772 4621; Fax: +65 6777 5545; E-mail: gohbc{at}nuh.com.sg
Background: Intracellular gemcitabine triphosphate (dFdCTP) levels can be optimised by administering gemcitabine at a fixed dose rate infusion.
Patients and methods: Patients with chemonaive advanced non-small cell lung cancer (NSCLC) were randomised to receive gemcitabine at a fixed dose rate gemcitabine 750 mg/m2 over 75 min (arm A) or gemcitabine 1000 mg/m2 over 30 min (arm B) on days 1 and 8 every three week cycle. Carboplatin at AUC of 5 was administered in both treatment arms on day 1 of each cycle. End points were activity, tolerability and pharmacokinetics of plasma and intracellular gemcitabine.
Results: 76 patients were randomised. Response rate was 34% in arm A and 42% in arm B. Toxicity and quality of life scores were similar for both treatment arms. Mean plasma Cmaxgemcitabine and mean dFdCTP AUC in arm A was 20.8 µM ± 17.2 µM and 35 079 ± 18 216 µM*min respectively and in arm B, 41.2 ± 13.9 µM and 32 249 ± 11 267 µM*min respectively. dFdCTP saturation was reached in Arm B but not in Arm A.
Conclusion: The saturability of dFdCTP accumulation in Arm A suggests optimal delivery of gemcitabine is achieved using fixed rate infusion compared to 30-min infusion. Fixed dose rate gemcitabine is active and feasible, supporting the concept of fixed dosing rate of gemcitabine in advanced NSCLC. However, this entails a longer infusion time with associated higher costs involved.
Key words: gemcitabine, non-small cell lung cancer, pharmacokinetics
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