Phase II Evaluation of Docetaxel-Modulated Capecitabine in Previously Treated Patients with Non–Small Cell Lung Cancer

Abstract

Purpose: Based on the preclinical observation of upregulation of thymidine phosphorylase, the last enzymatic step in the conversion of capecitabine to 5-fluorouracil, by docetaxel along with good clinical tolerability of the combination of docetaxel and capecitabine using an optimized schedule in a previous phase I trial, we conducted this phase II study of this combination in patients with refractory or relapsed non --small cell lung cancer (NSCLC).Patients and Methods: Patients with NSCLC previously treated with at least one platinum-or paclitaxel-based regimen received docetaxel 36 mg/m 2 on days 1, 8, and 15 and capecitabine 625 mg/m 2 twice daily on days 5 to 18, every 4 weeks. The primary objective of the study was evaluation of progression-free survival (PFS) 26 weeks from initiation of treatment.Results: Thirty-six evaluable patients received 104 cycles of the combination. Severe toxicities were infrequent with only one patient requiring toxicity-related hospitalization. The 26-week PFS rate was 25% (95% confidence interval, 12-42) with an intent to treat median survival and 1-year survival rate of 9.1 months and 37%, respectively. Among 31 patients with measurable disease (Response Evaluation Criteria in Solid Tumors criteria), eight (26%; 95% confidence interval, 12-45) achieved partial responses.Conclusion: The combination of capecitabine and weekly docetaxel is well tolerated in previously treated patients with NSCLC. The relatively high 26-week PFS and 1-year survival, as well as the high response rate observed, encourages further evaluation of this regimen in NSCLC, either in randomized trials for refractory patients or as a potential treatment option for chemotherapy naive patients.

Phase II trial of capecitabine combined with docetaxel in previously treated patients with non-small cell lung cancer: A randomized controlled study

“…No dose reduction was caused by HFS, suggesting that this combination regimen was well-tolerated and practical for clinical implementation. Compared with other similar studies, the incidence of HFS in our study was fairly low, and severe fatigue, neutropenia and anemia were milder (7,8).…”

“…Previous studies of human cancer xenografts showed that docetaxel upregulated thymidine phospharylase (TP) activity, and that docetaxel combined with capecitabine had a synergistic effect (6). Certain phase II trials have verified the preliminary efficacy and safety of capecitabine combined with docetaxel (7,8). As Chinese and Korean all belong to the Oriental population in Asia, our study adopted the recommended dose of the research on Koreans of a phase II trial (8).…”

“…The preclinical study indicated that the effect of docetaxel on the upregulation of TP activity was strongest between days 6 and 10 following administration, which was proven by clinical trials (6,7). Therefore, we adjusted the administration time of the Korean regimen; subsequently, capecitabine was orally administered initially on day 5 of treatment instead of day 1.…”

“…In breast cancer, capecitabine combined with docetaxel demonstrated a longer time to progression (TTP) and better overall survival (OS) than docetaxel alone (5). Both theoretical and clinical research prove that a combination of the two is effective in the treatment of NSCLC (6)(7)(8)(9). However, to the best of our knowledge, there is no study comparing the efficacy of capecitabine combined with docetaxel and docetaxel alone in previously treated patients with NSCLC.…”

Capecitabine in combination with docetaxel and mitomycin C in patients with pre-treated tumours: results of an extended phase-I trial

“…This randomised trial revealed that the combination of both drugs provided clear benefits over single-agent docetaxel in terms of objective tumour response rate (42 vs 30%), time to progression (median, 6.1 vs 4.2 months), and overall survival (median, 14.5 vs 11.5 months). Furthermore, several phase-II studies on the combination of capecitabine and docetaxel showed activity in patients with metastatic gastric cancer (Chun et al, 2005;Giordano et al, 2006), metastatic oesophageal cancer (Lorenzen et al, 2005), advanced non-small cell lung cancer (Han et al, 2003;Kindwall-Keller et al, 2005), and prostate cancer (Morant et al, 2004;Ferrero et al, 2006).…”