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

Soo, Ross A.; Wang, L. Z.; Tham, Lai-San; Yong, Wei‐Peng; Boyer, Michael; Lim, Hui Jun; Lee, H. S.; Millward, Michael; Liang, Shinn-Jye; Beale, Philip; Lee, S. C.; Goh, Boon-Cher

doi:10.1093/annonc/mdl084

Cited by 38 publications

(51 citation statements)

References 16 publications

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“…There is very limited data exploring the relationship between the pharmacokinetics of intracellular GEM-TP and toxicity. No relationship was seen in combination with Carboplatin ( Soo et al, 2006) In our data GEM-TP cMax correlate with AUC and was used for pharmacodynamic correlations. Modelling GEM-TP concentrations to % reduction in white cells improved the fit of the model although the relationship remained modest (r 2 = 0.3739) (Grimison et al, 2007).…”

Section: Pharmacokinetic/pharmacodynamic Relationshipsmentioning

confidence: 64%

One Step Closer to the Target: Intracellular Pharmacokinetics of Gemcitabine

Links¹,

Galettis²

2012

Readings in Advanced Pharmacokinetics - Theory, Methods and Applications

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Section: Pharmacokinetic/pharmacodynamic Relationshipsmentioning

confidence: 64%

One Step Closer to the Target: Intracellular Pharmacokinetics of Gemcitabine

Links¹,

Galettis²

2012

Readings in Advanced Pharmacokinetics - Theory, Methods and Applications

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“…When a standard 30-min infusion was employed, gemcitabine doses ranged from 800 to 2,200 mg/m 2 [5,[13][14][15][16]. When gemcitabine was administered as a FDR infusion of 10 mg/m 2 /min, infusion times ranged from 75 to 150 min [5,16]. Although in our study FDR was the same, the infusion times were different, i.e.…”

Section: Discussionmentioning

confidence: 82%

“…Various studies have evaluated intracellular dFdCTP concentrations in PBMC after gemcitabine treatment in patients with solid tumors [5,[13][14][15][16]. However, it is difficult to compare our results with those of the literature because the published studies were performed administering gemcitabine at variable doses and with variable infusion times.…”

Section: Discussionmentioning

confidence: 98%

“…However, it is difficult to compare our results with those of the literature because the published studies were performed administering gemcitabine at variable doses and with variable infusion times. When a standard 30-min infusion was employed, gemcitabine doses ranged from 800 to 2,200 mg/m 2 [5,[13][14][15][16]. When gemcitabine was administered as a FDR infusion of 10 mg/m 2 /min, infusion times ranged from 75 to 150 min [5,16].…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer

Caffo

Fallani

Marangon

et al. 2010

Cancer Chemother Pharmacol

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Iris Cassetta, et al.. Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer. Cancer Chemotherapy and Pharmacology, Springer Verlag, 2010, 65 (6), pp.1197-1202. <10.1007/s00280-010-1255-7>. SHORT COMMUNICATIONPharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer Results The plasmatic pharmacokinetic parameters were clearly different when the patients received a higher gemcitabine dose in the second cycle compared to the lower dose of the first course; in the same time, the intracellular drug levels were not modified. Comparing the pharmacokinetic parameters of different patients treated at different dose levels, the results appeared to be quite similar. Conclusions A substantially higher accumulation of metabolites in peripheral blood mononuclear cells was observed when the longer infusion time was employed, suggesting a pharmacological advantage for this treatment schedule.

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“…Patients receiving FDR infusion experienced more hematological toxicities than patients treated with standard gemcitabine: grade 3 or 4 thrombocytopenia, 37.2% versus 10.2%; neutropenia, 48.8% versus 26.5%; and grade 4 anemia, 9.3% versus 2%. In summary, although the results have to be interpreted carefully, the [84]. The mean AUC of dFdCTP in blood mononuclear cells, however, was comparable between the two dosing schedules (Table 2).…”

Section: Phase Ii/iii Randomized Trials Comparing Fdr With Standard Dmentioning

confidence: 83%

Prolonged Versus Standard Gemcitabine Infusion: Translation of Molecular Pharmacology to New Treatment Strategy

2008

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After completing this course, the reader will be able to:1. Describe the molecular pharmacology of nucleoside analogues.2. Explain transport, metabolism, and elimination in relation to the activity of gemcitabine.3. Describe the clinical pharmacology of gemcitabine in relation to its rate of administration.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTGemcitabine is frequently used in the treatment of patients with solid tumors. Gemcitabine is taken up into the cell via human nucleoside transporters (hNTs) and is intracellularly phosphorylated by deoxycytidine kinase (dCK) to its monophosphate and subsequently into its main active triphosphate metabolite 2,2-difluorodeoxycytidine triphosphate (dFdCTP), which is incorporated into DNA and inhibits DNA synthesis. In addition, gemcitabine is extensively deaminated to 2,2-difluorodeoxyuridine, which is largely excreted into the urine. High expression levels of human equilibrative nucleoside transporter type 1 were associated with a significantly longer overall survival duration after gemcitabine treatment in patients with pancreatic cancer.Clinical studies in blood mononuclear and leukemic cells demonstrated that a lower infusion rate of gemcitabine was associated with higher intracellular dFdCTP levels. Prolonged infusion of gemcitabine at a fixed dose rate (FDR) of 10 mg/m 2 per minute was associated with a higher intracellular accumulation of dFdCTP, greater toxicity, and a higher response rate than with the standard 30-minute infusion of gemcitabine in patients with pancreatic cancer.In the current review, we discuss the molecular pharmacology of nucleoside analogues and the influence of hNTs and dCK on the activity and toxicity of gemcitabine, which is the basis for clinical studies on

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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

Cited by 38 publications

References 16 publications

One Step Closer to the Target: Intracellular Pharmacokinetics of Gemcitabine

One Step Closer to the Target: Intracellular Pharmacokinetics of Gemcitabine

Pharmacokinetic study of gemcitabine, given as prolonged infusion at fixed dose rate, in combination with cisplatin in patients with advanced non-small-cell lung cancer

Prolonged Versus Standard Gemcitabine Infusion: Translation of Molecular Pharmacology to New Treatment Strategy

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