TY - JOUR
T1 - A phase I/II study of pemetrexed vinorelbine in patients with non-small cell lung cancer
AU - Clarke, S.J.
AU - Boyer, M.J.
AU - Millward, Michael
AU - Underhill, C.
AU - Moyland, E.
AU - Yip, D.
AU - White, S.
AU - Childs, A.
AU - Beale, P.
AU - Latz, J.
AU - Suri, A.
AU - Iglesias, J.L.
PY - 2005
Y1 - 2005
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/ m(2)) and vinorelbine (days 1 and 8, 15-30 mg/m(2)) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B-12 supplementation were given. Results: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700mg/m(2) and vinorelbine 30mg/m(2); and recommended phase II dose was pemetrexed 500mg/m(2) and vinorelbine 30 mg/m(2). 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%), white 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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/ m(2)) and vinorelbine (days 1 and 8, 15-30 mg/m(2)) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B-12 supplementation were given. Results: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700mg/m(2) and vinorelbine 30mg/m(2); and recommended phase II dose was pemetrexed 500mg/m(2) and vinorelbine 30 mg/m(2). 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%), white 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
U2 - 10.1016/j.lungcan.2005.04.003
DO - 10.1016/j.lungcan.2005.04.003
M3 - Article
C2 - 15923057
VL - 49
SP - online - approx 5-20pp
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
IS - 3
ER -
