Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery infusion and intravenous infusion

Abeer F. Alharbi, Robert A Kratzke, Jonathan D’Cunha, Michael A Maddaus, Kinjal J Sanghavi, Mark N Kirstein

Research output: Contribution to journalArticle

Abstract

Purpose: We investigated the safety, pharmacokinetics, and efficacy of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients. Methods: Patients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600 mg/m 2 on day one of cycle one, followed by IV as 1000 mg/m 2 on day eight of cycle one, and IV on days one and eight of all subsequent cycles. Pharmacokinetics for gemcitabine and dFdU metabolite in plasma, and dFdCTP active metabolite in peripheral blood mononuclear cells (PBMC) were evaluated. Intensive pharmacokinetic sampling was performed after BAI and IV infusions during cycle one. Results: Three male patients (age range 59–68 years) were evaluated. All patients responded with stable disease or better. One PR was observed after cycle three, and the remaining had SD. C max (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 7.71 ± 0.13, 66.5 ± 40.6, and 38 ± 6.27 µM and following IV infusion, 17 ± 2.36, 50.8 ± 3.61, and 83.2 ± 12.3 µM, respectively. The AUCinf (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 6.89 ± 1.2, 791.1 ± 551.2, and 829.9 ± 217.8 µM h and following IV infusion, 12.5 ± 3.13, 584 ± 86.6, and 1394.64 ± 682.2 µM h, respectively. The AUC and Cmax of dFdCTP after BAI were higher than IV. The median OS was 6.27 months. No grade 3 or 4 toxicity was observed. The most common side effects were all grade ≤ 2 involving nausea, vomiting, rigor, thrombocytopenia, and anemia. Conclusions: Systemic exposure to dFdCTP was higher after BAI than IV in two out of three patients.

Original languageEnglish (US)
Pages (from-to)387-391
Number of pages5
JournalCancer chemotherapy and pharmacology
Volume83
Issue number2
DOIs
StatePublished - Feb 5 2019

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gemcitabine
Bronchial Arteries
Pharmacokinetics
Metabolites
Intravenous Infusions
Chemotherapy
Toxicity
Blood
Sampling
Thrombocytopenia
Nausea
Plasmas
Area Under Curve
Vomiting
Anemia
Blood Cells

Keywords

  • BAI
  • Gemcitabine
  • IV infusion
  • NSCLC
  • PK

PubMed: MeSH publication types

  • Journal Article

Cite this

Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery infusion and intravenous infusion. / Alharbi, Abeer F.; Kratzke, Robert A; D’Cunha, Jonathan; Maddaus, Michael A; Sanghavi, Kinjal J; Kirstein, Mark N.

In: Cancer chemotherapy and pharmacology, Vol. 83, No. 2, 05.02.2019, p. 387-391.

Research output: Contribution to journalArticle

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AU - Alharbi, Abeer F.

AU - Kratzke, Robert A

AU - D’Cunha, Jonathan

AU - Maddaus, Michael A

AU - Sanghavi, Kinjal J

AU - Kirstein, Mark N

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N2 - Purpose: We investigated the safety, pharmacokinetics, and efficacy of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients. Methods: Patients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600 mg/m 2 on day one of cycle one, followed by IV as 1000 mg/m 2 on day eight of cycle one, and IV on days one and eight of all subsequent cycles. Pharmacokinetics for gemcitabine and dFdU metabolite in plasma, and dFdCTP active metabolite in peripheral blood mononuclear cells (PBMC) were evaluated. Intensive pharmacokinetic sampling was performed after BAI and IV infusions during cycle one. Results: Three male patients (age range 59–68 years) were evaluated. All patients responded with stable disease or better. One PR was observed after cycle three, and the remaining had SD. C max (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 7.71 ± 0.13, 66.5 ± 40.6, and 38 ± 6.27 µM and following IV infusion, 17 ± 2.36, 50.8 ± 3.61, and 83.2 ± 12.3 µM, respectively. The AUCinf (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 6.89 ± 1.2, 791.1 ± 551.2, and 829.9 ± 217.8 µM h and following IV infusion, 12.5 ± 3.13, 584 ± 86.6, and 1394.64 ± 682.2 µM h, respectively. The AUC and Cmax of dFdCTP after BAI were higher than IV. The median OS was 6.27 months. No grade 3 or 4 toxicity was observed. The most common side effects were all grade ≤ 2 involving nausea, vomiting, rigor, thrombocytopenia, and anemia. Conclusions: Systemic exposure to dFdCTP was higher after BAI than IV in two out of three patients.

AB - Purpose: We investigated the safety, pharmacokinetics, and efficacy of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients. Methods: Patients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600 mg/m 2 on day one of cycle one, followed by IV as 1000 mg/m 2 on day eight of cycle one, and IV on days one and eight of all subsequent cycles. Pharmacokinetics for gemcitabine and dFdU metabolite in plasma, and dFdCTP active metabolite in peripheral blood mononuclear cells (PBMC) were evaluated. Intensive pharmacokinetic sampling was performed after BAI and IV infusions during cycle one. Results: Three male patients (age range 59–68 years) were evaluated. All patients responded with stable disease or better. One PR was observed after cycle three, and the remaining had SD. C max (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 7.71 ± 0.13, 66.5 ± 40.6, and 38 ± 6.27 µM and following IV infusion, 17 ± 2.36, 50.8 ± 3.61, and 83.2 ± 12.3 µM, respectively. The AUCinf (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 6.89 ± 1.2, 791.1 ± 551.2, and 829.9 ± 217.8 µM h and following IV infusion, 12.5 ± 3.13, 584 ± 86.6, and 1394.64 ± 682.2 µM h, respectively. The AUC and Cmax of dFdCTP after BAI were higher than IV. The median OS was 6.27 months. No grade 3 or 4 toxicity was observed. The most common side effects were all grade ≤ 2 involving nausea, vomiting, rigor, thrombocytopenia, and anemia. Conclusions: Systemic exposure to dFdCTP was higher after BAI than IV in two out of three patients.

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