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 < 0.07 nmol/min/mg protein were considered ineligible for the study. Treatment included a 28-day cycle of docetaxel 36 mg/m(2) on days 1, 8, 15 and capecitabine 1250 mg/m(2)/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.
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 NSCLCpatients. 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 < 0.07 nmol/min/mg protein were considered ineligible for the study. Treatment included a 28-day cycle of docetaxel 36 mg/m(2) on days 1, 8, 15 and capecitabine 1250 mg/m(2)/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.
Authors: J Saito; Y Nakai; Y Saijo; T Nukiwa; S Koinumaru; Y Matsuura; N Aso; Y Yamane; T Tsukamoto; T Sayama; T Nakabayashi Journal: Lung Cancer Date: 2001 Feb-Mar Impact factor: 5.705
Authors: Joan H Schiller; David Harrington; Chandra P Belani; Corey Langer; Alan Sandler; James Krook; Junming Zhu; David H Johnson Journal: N Engl J Med Date: 2002-01-10 Impact factor: 91.245
Authors: Su Jin Shin; Hawk Kim; Jin Ho Baek; Jong-Joon Ahn; Yangjin Jegal; Kwang Won Seo; Chang Ryul Park; Je Kyoun Shin; Jong Pil Jung; Jeong Won Kim; Hee Jeong Cha; Woon Jung Kwon; Ae Kyung Jeong; Young Ju Noh; Jae-Hoo Park; Young Joo Min Journal: Lung Cancer Date: 2007-11-14 Impact factor: 5.705