A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer

Stephen J. Clarke; Michael J. Boyer; Michael Millward; Craig Underhill; Eugene Moylan; Desmond Yip; Shane White; Annabel Childs; Phillip Beale; Jane Latz; Ajit Suri; Jose L. Iglesias

doi:10.1016/j.lungcan.2005.04.003

A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer

Stephen J. Clarke^*, Michael J. Boyer, Michael Millward, Craig Underhill, Eugene Moylan, Desmond Yip, Shane White, Annabel Childs, Phillip Beale, Jane Latz, Ajit Suri, Jose L. Iglesias

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Purpose: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. Experimental design: Phase I pts received pemetrexed (day 1, 300-700 mg/m²) and vinorelbine (days 1 and 8, 15-30 mg/m²) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B₁₂ supplementation were given. Results: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m² and vinorelbine 30 mg/m²; and recommended phase II dose was pemetrexed 500 mg/m ² and vinorelbine 30 mg/m². When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). Conclusion: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.

Original language	English
Pages (from-to)	401-412
Number of pages	12
Journal	Lung Cancer
Volume	49
Issue number	3
DOIs	https://doi.org/10.1016/j.lungcan.2005.04.003
Publication status	Published - Sept 2005
Externally published	Yes

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10.1016/j.lungcan.2005.04.003

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@article{03921a9421fd4dbc8889757021b5d1ba,

title = "A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer",

abstract = "Purpose: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. Experimental design: Phase I pts received pemetrexed (day 1, 300-700 mg/m2) and vinorelbine (days 1 and 8, 15-30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given. Results: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m 2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). Conclusion: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.",

keywords = "First-line treatment, MTD, Non-small cell lung cancer, Pemetrexed, Pharmacokinetics, Tumor response, Vinorelbine",

author = "Clarke, {Stephen J.} and Boyer, {Michael J.} and Michael Millward and Craig Underhill and Eugene Moylan and Desmond Yip and Shane White and Annabel Childs and Phillip Beale and Jane Latz and Ajit Suri and Iglesias, {Jose L.}",

year = "2005",

month = sep,

doi = "10.1016/j.lungcan.2005.04.003",

language = "English",

volume = "49",

pages = "401--412",

journal = "Lung Cancer",

issn = "0169-5002",

publisher = "Elsevier Ireland Ltd",

number = "3",

}

TY - JOUR

T1 - A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer

AU - Clarke, Stephen J.

AU - Boyer, Michael J.

AU - Millward, Michael

AU - Underhill, Craig

AU - Moylan, Eugene

AU - Yip, Desmond

AU - White, Shane

AU - Childs, Annabel

AU - Beale, Phillip

AU - Latz, Jane

AU - Suri, Ajit

AU - Iglesias, Jose L.

PY - 2005/9

Y1 - 2005/9

N2 - Purpose: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. Experimental design: Phase I pts received pemetrexed (day 1, 300-700 mg/m2) and vinorelbine (days 1 and 8, 15-30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given. Results: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m 2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). Conclusion: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.

AB - Purpose: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. Experimental design: Phase I pts received pemetrexed (day 1, 300-700 mg/m2) and vinorelbine (days 1 and 8, 15-30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given. Results: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m 2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). Conclusion: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.

KW - First-line treatment

KW - MTD

KW - Non-small cell lung cancer

KW - Pemetrexed

KW - Pharmacokinetics

KW - Tumor response

KW - Vinorelbine

UR - http://www.scopus.com/inward/record.url?scp=23744482948&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2005.04.003

DO - 10.1016/j.lungcan.2005.04.003

M3 - Article

SN - 0169-5002

VL - 49

SP - 401

EP - 412

JO - Lung Cancer

JF - Lung Cancer

IS - 3

ER -

A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer

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