TY - JOUR
T1 - A phase II study of modulated-capecitabine and docetaxel in chemonaive patients with advanced non-small cell lung cancer (NSCLC)
AU - Bertino, Erin M.
AU - Bekaii-Saab, Tanios
AU - Fernandez, Soledad
AU - Diasio, Robert B.
AU - Karim, Nagla A.
AU - Otterson, Gregory A.
AU - Villalona-Calero, Miguel A.
N1 - Funding Information:
Clinical trial financial support was provided by National Institute of Health Exploratory/Developmental Research Grant Award (R21 - CA108157). Additional financial support provided by Hoffmann-La Roche Inc and Sanofi-Aventis . The study sponsors were involved in study design but were not involved in data analysis/interpretation or manuscript preparation and submission.
PY - 2013/1
Y1 - 2013/1
N2 - Introduction: This phase II single-arm trial of docetaxel and capecitabine in previously untreated non-small cell lung cancer (NSCLC) patients was designed to evaluate response rate of this regimen based on promising efficacy data from phase II testing in pre-treated NSCLC patients. The trial also evaluated the correlation between peripheral blood dihydropyrimidine dehydrogenase (DPD) expression and efficacy/toxicity. Methods: Patients with advanced NSCLC (metastatic, including malignant pleural effusion) without prior chemotherapy were enrolled. Baseline DPD screening was performed; patients with baseline DPD level <0.07nmol/min/mg protein were considered ineligible for the study. Treatment included a 28-day cycle of docetaxel 36mg/m2 on days 1, 8, 15 and capecitabine 1250mg/m2/day in divided doses on days 5-18. Overall response rate (RR) was the primary endpoint with a target RR of 50%. Correlative studies included evaluation of DPD activity levels in peripheral blood and correlation with clinical responses. Results: Twenty-eight patients received 86 cycles of treatment (median 3 cycles) and were evaluable for response. The RR was 18% (5 patients); RR did not meet the pre-specified efficacy endpoint and the trial was stopped. 14 patients had stable disease (SD - 50%) and 4 patients had SD > 12 weeks. Median time to progression was 3.3 months (95% CI 1.5-4.6 months). Median overall survival was 10.5 months (95% CI: 3.2-15 months). Main toxicities included fatigue, stomatitis and leukopenia. DPD levels ranged from 0.06 to 0.26. nmol/min/mg. The majority of responders (4/5) had DPD levels ≤0.1. nmol/min/mg. Most of the responders (4/5) experienced grade 3 toxicities including leukopenia, dehydration, fatigue, and diarrhea. None of the patients (0/4) with higher DPD levels (>0.2. nmol/min/mg) had a response. Conclusion: The response rate for the regimen did not demonstrate sufficient activity and further study of this regimen in this setting is not indicated. Interestingly, the results suggest that low DPD expression may be associated with response to capecitabine but also with increased toxicity.
AB - Introduction: This phase II single-arm trial of docetaxel and capecitabine in previously untreated non-small cell lung cancer (NSCLC) patients was designed to evaluate response rate of this regimen based on promising efficacy data from phase II testing in pre-treated NSCLC patients. The trial also evaluated the correlation between peripheral blood dihydropyrimidine dehydrogenase (DPD) expression and efficacy/toxicity. Methods: Patients with advanced NSCLC (metastatic, including malignant pleural effusion) without prior chemotherapy were enrolled. Baseline DPD screening was performed; patients with baseline DPD level <0.07nmol/min/mg protein were considered ineligible for the study. Treatment included a 28-day cycle of docetaxel 36mg/m2 on days 1, 8, 15 and capecitabine 1250mg/m2/day in divided doses on days 5-18. Overall response rate (RR) was the primary endpoint with a target RR of 50%. Correlative studies included evaluation of DPD activity levels in peripheral blood and correlation with clinical responses. Results: Twenty-eight patients received 86 cycles of treatment (median 3 cycles) and were evaluable for response. The RR was 18% (5 patients); RR did not meet the pre-specified efficacy endpoint and the trial was stopped. 14 patients had stable disease (SD - 50%) and 4 patients had SD > 12 weeks. Median time to progression was 3.3 months (95% CI 1.5-4.6 months). Median overall survival was 10.5 months (95% CI: 3.2-15 months). Main toxicities included fatigue, stomatitis and leukopenia. DPD levels ranged from 0.06 to 0.26. nmol/min/mg. The majority of responders (4/5) had DPD levels ≤0.1. nmol/min/mg. Most of the responders (4/5) experienced grade 3 toxicities including leukopenia, dehydration, fatigue, and diarrhea. None of the patients (0/4) with higher DPD levels (>0.2. nmol/min/mg) had a response. Conclusion: The response rate for the regimen did not demonstrate sufficient activity and further study of this regimen in this setting is not indicated. Interestingly, the results suggest that low DPD expression may be associated with response to capecitabine but also with increased toxicity.
KW - Capecitabine
KW - Dihydropyrimidine deficiency
KW - Non-small cell lung cancer
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U2 - 10.1016/j.lungcan.2012.09.013
DO - 10.1016/j.lungcan.2012.09.013
M3 - Article
C2 - 23079156
AN - SCOPUS:84871052576
SN - 0169-5002
VL - 79
SP - 27
EP - 32
JO - Lung Cancer
JF - Lung Cancer
IS - 1
ER -
