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A phase 1b trial of the combination of an all-oral regimen of capecitabine and erlotinib in advanced non-small cell lung cancer in Caucasian patients.

Authors :
Kumar R
Lu SK
Minchom A
Sharp A
Davidson M
Gunapala R
Yap TA
Bhosle J
Popat S
O'Brien ME
Source :
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2016 Feb; Vol. 77 (2), pp. 375-83. Date of Electronic Publication: 2015 Dec 26.
Publication Year :
2016

Abstract

Purpose: Erlotinib is active in advanced non-small cell lung cancer (aNSCLC) particularly in patients with EGFR-sensitizing mutations. The thymidylate synthase inhibitors are active in NSCLC, but capecitabine is not well studied. This study explored the safety and activity of this oral combination.<br />Methods: This phase Ib trial used a 3 + 3 escalation design with a combination of erlotinib (100 mg daily) with increasing doses of capecitabine (500, 750 and 1000 mg/m(2) BD, 14/21 days), in first- and second-line aNSCLC of adenocarcinoma histology. The DLT was any drug-induced toxicity ≥grade (G)2 causing dose interruption or dose delay during the first 2 cycles.<br />Results: Forty patients were recruited, and 1 patient had an EGFR mutation. Dose escalation stopped at capecitabine 1000 mg/m(2) with expansion to 6 patients due to unpredicted DLTs in 2/6 patients: G2 creatinine rise, G2 anaemia, G3 atrial fibrillation and G3 pneumonia. MTD was capecitabine 750 mg/m(2). First-line dose escalation at the MTD led to unpredicted DLTs in 3/4 patients (G3 troponin rise, G2 rash and G2 hyperbilirubinaemia). MTD expansion in the second-line setting was well tolerated. The most common drug toxicities were gastrointestinal (35 %), followed by skin disorders (28 %). The response rate was 3 % with a disease control rate of 34 %. Median progressive-free survival was 1.6 months (95 % CI 1.4-3.5), and median overall survival was 6.1 months (95 % CI 5.1-10.1).<br />Conclusion: The MTD for the combination of capecitabine and erlotinib is 750 mg/m(2) BD, 14/21 days, and 100 mg daily, respectively, which is lower than predicted. Capecitabine did not improve the efficacy of erlotinib in aNSCLC unselected for EGFR mutation.

Details

Language :
English
ISSN :
1432-0843
Volume :
77
Issue :
2
Database :
MEDLINE
Journal :
Cancer chemotherapy and pharmacology
Publication Type :
Academic Journal
Accession number :
26706729
Full Text :
https://doi.org/10.1007/s00280-015-2950-1