Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: a randomized phase II study

Su Jin Lee, Sungmin Kim, Moonjin Kim, Jeeyun Lee, Yeon Hee Park, Young-Hyuck Im, Se Hoon Park, Su Jin Lee, Sungmin Kim, Moonjin Kim, Jeeyun Lee, Yeon Hee Park, Young-Hyuck Im, Se Hoon Park

Abstract

Background: The aim of this study was to assess the efficacy and safety of a combination regimen of capecitabine plus cisplatin (CC) or capecitabine plus paclitaxel (CP) as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma.

Methods: Patients with recurrent or metastatic esophageal squamous cell carcinoma were enrolled in this open-label, phase II, randomized trial. Patients were assigned to either the CC arm (days [D]1-14 capecitabine 1000 mg/m(2) twice daily + D1 cisplatin 75 mg/m(2), every 3 weeks) or the CP arm (D1-14 capecitabine 1000 mg/m(2) twice daily + D1, 8 paclitaxel 80 mg/m(2), every 3 weeks). The primary endpoint of the study was response rate and secondary endpoints were progression-free survival (PFS), overall survival (OS), toxicity and quality of life.

Results: A total of 94 patients were entered into this study between October 2008 and October 2012, 46 patients in the CC arm and 48 in the CP arm. Patients in both arms received a median of six cycles of treatment (range, 1-14) and the response rates were 57 and 58 % in the cisplatin and paclitaxel arm, respectively. With a median follow-up of 23 months, the median PFS was 5.1 months (95 % CI 4.0-6.2 months) in the cisplatin arm and 6.7 months (95 % CI 4.9-8.5 months) in the paclitaxel arm, whereas the median OS was 10.5 months (95 % CI 9.2-11.9 months) in the cisplatin arm and 13.2 months (95 % CI 9.4-17.0 months) in the paclitaxel arm. Patients in the cisplatin arm were more likely to experience neutropenia and thrombocytopenia, whereas patients in the paclitaxel arm had a higher frequency of neuropathy and alopecia. Quality of life was similar between treatment arms.

Conclusions: Both CC and CP regimens were effective and well tolerated as a first-line treatment in patients with metastatic esophageal squamous cell carcinoma.

Figures

Fig. 1
Fig. 1
Flow diagram of all registered patients
Fig. 2
Fig. 2
Progression-free survival for the capecitabine plus paclitaxel arm (CP, solid line) and capecitabine plus cisplatin arm (CC, dotted line)
Fig. 3
Fig. 3
Overall survival for the capecitabine plus paclitaxel arm (CP, solid line) and capecitabine plus cisplatin arm (CC, dotted line)

References

    1. Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24:2137–50. doi: 10.1200/JCO.2005.05.2308.
    1. Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Cancer statistics in Korea: incidence, mortality, survival and prevalence in 2010. Cancer Res Treat. 2013;45:1–14. doi: 10.4143/crt.2013.45.1.1.
    1. Enzinger PC, Ilson DH, Kelsen DP. Chemotherapy in esophageal cancer. Semin Oncol. 1999;26:12–20.
    1. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358:36–46. doi: 10.1056/NEJMoa073149.
    1. Bleiberg H, Conroy T, Paillot B, Lacave AJ, Blijham G, Jacob JH, et al. Randomised phase II study of cisplatin and 5-fluorouracil (5-FU) versus cisplatin alone in advanced squamous cell oesophageal cancer. Eur J Cancer. 1997;33:1216–20. doi: 10.1016/S0959-8049(97)00088-9.
    1. Levard H, Pouliquen X, Hay JM, Fingerhut A, Langlois-Zantain O, Huguier M, et al. 5-Fluorouracil and cisplatin as palliative treatment of advanced oesophageal squamous cell carcinoma. A multicentre randomised controlled trial. The French Associations for Surgical Research. Eur J Surg. 1998;164:849–57. doi: 10.1080/110241598750005273.
    1. Lee J, Im YH, Cho EY, Hong YS, Lee HR, Kim HS, et al. A phase II study of capecitabine and cisplatin (XP) as first-line chemotherapy in patients with advanced esophageal squamous cell carcinoma. Cancer Chemother Pharmacol. 2008;62:77–84. doi: 10.1007/s00280-007-0577-6.
    1. Polee MB, Eskens FA, van der Burg ME, Splinter TA, Siersema PD, Tilanus HW, et al. Phase II study of bi-weekly administration of paclitaxel and cisplatin in patients with advanced oesophageal cancer. Br J Cancer. 2002;86:669–73. doi: 10.1038/sj.bjc.6600166.
    1. Zhang X, Shen L, Li J, Li Y, Li J, Jin M. A phase II trial of paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus. Am J Clin Oncol. 2008;31:29–33. doi: 10.1097/COC.0b013e3181131ca9.
    1. Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res. 1998;4:1013–9.
    1. Uhlmann C, Ballabeni P, Rijken N, Brauchli P, Mingrone W, Rauch D, et al. Capecitabine with weekly paclitaxel for advanced breast cancer: a phase I dose-finding trial. Oncology. 2004;67:117–22. doi: 10.1159/000080997.
    1. Blum JL, Dees EC, Chacko A, Doane L, Ethirajan S, Hopkins J, et al. Phase II trial of capecitabine and weekly paclitaxel as first-line therapy for metastatic breast cancer. J Clin Oncol. 2006;24:4384–90. doi: 10.1200/JCO.2005.05.1383.
    1. Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989;10:1–10. doi: 10.1016/0197-2456(89)90015-9.
    1. Yun T, Han JY, Lee JS, Choi HL, Kim HY, Nam BH, et al. Phase II study of weekly paclitaxel and capecitabine in patients with metastatic or recurrent esophageal squamous cell carcinoma. BMC Cancer. 2011;11:385. doi: 10.1186/1471-2407-11-385.
    1. Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001;19:4097–106.
    1. Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001;19:2282–92.
    1. Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, et al. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009;20:666–73. doi: 10.1093/annonc/mdn717.
    1. Lee SS, Kim SB, Park SI, Kim YH, Ryu JS, Song HY, et al. Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer. Jpn J Clin Oncol. 2007;37:829–35. doi: 10.1093/jjco/hym117.
    1. Qin TJ, An GL, Zhao XH, Tian F, Li XH, Lian JW, et al. Combined treatment of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer. World J Gastroenterol. 2009;15:871–6. doi: 10.3748/wjg.15.871.
    1. van Meerten E, Eskens FA, van Gameren EC, Doorn L, van der Gaast A. First-line treatment with oxaliplatin and capecitabine in patients with advanced or metastatic oesophageal cancer: a phase II study. Br J Cancer. 2007;96:1348–52.
    1. Lorenzen S, Duyster J, Lersch C, von Delius S, Hennig M, Bredenkamp R, et al. Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial. Br J Cancer. 2005;92:2129–33. doi: 10.1038/sj.bjc.6602645.
    1. Dimopoulou I, Bamias A, Lyberopoulos P, Dimopoulos MA. Pulmonary toxicity from novel antineoplastic agents. Ann Oncol. 2006;17:372–9. doi: 10.1093/annonc/mdj057.

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