Abstract
Purpose
Metastatic colorectal cancer (MCRC) remains a significant public health concern. The objectives of present study are to investigate the efficacy and safety profile of capecitabine-based chemotherapy in the treatment of MCRC.
Materials and methods
We performed a computerized search using combinations of the following keywords: “metastatic colorectal cancer,” “Xeloda,” “chemotherapy,” “capecitabine,” or “5-fluorouracil.”
Results
Treatment with capecitabine chemotherapy was associated with a significantly prolonged progression-free survival (WMD = 1.24; 95% CI, 0.04–2.44; P = 0.04), whereas overall survival was not statistically significant (WMD [random] = 0.29; P = 0.75). Patients in both capecitabine and 5-fluorouracil groups had equal 1-, 2-, and 3-year survival (OR = 0.82, 95% CI: 0.59–1.12, P = 0.21; OR = 0.84, 95% CI: 0.61–1.15, P = 0.27; OR = 1.26, 95% CI: 0.78–2.05, P = 0.34; respectively). The analysis also demonstrates that the response rate of capecitabine-based chemotherapy was comparable to 5-fluorouracil-based chemotherapy (OR = 1.02, 95% CI, 0.90–1.14; P = 0.80). When comparing single-agent capecitabine against 5-fluorouracil/leucovorin, our results showed an overall OR of 1.56 (95% CI, 1.16–2.09) in favor of the capecitabine arm. When toxicity was evaluated, a statistically significant benefit with capecitabine-based therapy was seen, especially for grade 3/4 neutropenia (OR, 0.80; 95% CI, 0.71–0.91; P = 0.00005).
Conclusions
Capecitabine-based chemotherapy demonstrated a significantly superior progression-free survival, equivalent overall survival, and comparable response rate with 5-fluorouracil-based chemotherapy. These observations support the use of capecitabine-based chemotherapy in the treatment of MCRC as a first-line or as a neoadjuvant modality.
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References
Arkenau HT, Arnold D, Cassidy J, Diaz-Rubio E, Douillard JY, Hochster H, Martoni A, Grothey A, Hinke A, Schmiegel W, Schmoll HJ, Porschen R (2008) Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: a pooled analysis of randomized trials. J Clin Oncol 26:5910–5917
Cao Y, Liao C, Tan A, Liu L, Mo Z, Gao F (2010) Capecitabine plus oxaliplatin versus fluorouracil plus oxaliplatin as first line treatment for metastatic colorectal caner—meta-analysis of six randomized trials. Colorectal Dis 12:16–23
Cassidy J, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Saltz L (2008) Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol 26:2006–2012
Comella P, Massidda B, Filippelli G, Farris A, Natale D, Barberis G, Maiorino L, Palmeri S, Cannone M, Condemi G (2009) Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401. J Cancer Res Clin Oncol 135:217–226
Diaz-Rubio E, Tabernero J, Gomez-Espana A, Massuti B, Sastre J, Chaves M, Abad A, Carrato A, Queralt B, Reina JJ, Maurel J, Gonzalez-Flores E, Aparicio J, Rivera F, Losa F, Aranda E (2007) Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol 25:4224–4230
Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R (2001) 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 19:2282–2292
Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ (2005) Cancer statistics, 2005. CA Cancer J Clin 55:10–30
Kohne CH, De Greve J, Hartmann JT, Lang I, Vergauwe P, Becker K, Braumann D, Joosens E, Muller L, Janssens J, Bokemeyer C, Reimer P, Link H, Spath-Schwalbe E, Wilke HJ, Bleiberg H, Van Den Brande J, Debois M, Bethe U, Van Cutsem E (2008) Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol 19:920–926
Martoni AA, Pinto C, Di Fabio F, Lelli G, Rojas Llimpe FL, Gentile AL, Mutri V, Ballardini P, Giaquinta S, Piana E (2006) Capecitabine plus oxaliplatin (xelox) versus protracted 5-fluorouracil venous infusion plus oxaliplatin (pvifox) as first-line treatment in advanced colorectal cancer: a GOAM phase II randomised study (FOCA trial). Eur J Cancer 42:3161–3168
Narasimhan P, Narasimhan S, Hitti IF, Rachita M (2004) Serious hand-and-foot syndrome in black patients treated with capecitabine: report of 3 cases and review of the literature. Cutis 73:101–106
Okines AF, Norman AR, McCloud P, Kang YK, Cunningham D (2009) Meta-analysis of the REAL-2 and ML17032 trials: evaluating capecitabine-based combination chemotherapy and infused 5-fluorouracil-based combination chemotherapy for the treatment of advanced oesophago-gastric cancer. Ann Oncol 20:1529–1534
Porschen R, Arkenau HT, Kubicka S, Greil R, Seufferlein T, Freier W, Kretzschmar A, Graeven U, Grothey A, Hinke A, Schmiegel W, Schmoll HJ (2007) Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol 25:4217–4223
Reigner B, Watanabe T, Schuller J, Lucraft H, Sasaki Y, Bridgewater J, Saeki T, McAleer J, Kuranami M, Poole C, Kimura M, Monkhouse J, Yorulmaz C, Weidekamm E, Grange S (2003) Pharmacokinetics of capecitabine (Xeloda) in Japanese and Caucasian patients with breast cancer. Cancer Chemother Pharmacol 52:193–201
Rothenberg ML, Cox JV, Butts C, Navarro M, Bang YJ, Goel R, Gollins S, Siu LL, Laguerre S, Cunningham D (2008) Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol 19:1720–1726
Saif MW, Sandoval A (2008) Atypical hand-and-foot syndrome in an African American patient treated with capecitabine with normal DPD activity: is there an ethnic disparity? Cutan Ocul Toxicol 27:311–315
Sastre J, Aranda E, Massuti B, Tabernero J, Chaves M, Abad A, Carrato A, Reina JJ, Queralt B, Gomez-Espana A, Gonzalez-Flores E, Rivera F, Losa F, Garcia T, Sanchez-Rovira P, Maestu I, Diaz-Rubio E (2009) Elderly patients with advanced colorectal cancer derive similar benefit without excessive toxicity after first-line chemotherapy with oxaliplatin-based combinations: comparative outcomes from the 03-TTD-01 phase III study. Crit Rev Oncol Hematol 70:134–144
Skof E, Rebersek M, Hlebanja Z, Ocvirk J (2009) Capecitabine plus Irinotecan (XELIRI regimen) compared to 5-FU/LV plus Irinotecan (FOLFIRI regimen) as neoadjuvant treatment for patients with unresectable liver-only metastases of metastatic colorectal cancer: a randomised prospective phase II trial. BMC Cancer 9:120
Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J (2005) Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer 92:1976–1983
Tyagi P, Grothey A (2006) Commentary on a phase III trial of bevacizumab plus XELOX or FOLFOX4 for first-line treatment of metastatic colorectal cancer: the NO16966 trial. Clin Colorectal Cancer 6:261–264
Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P (2001) Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol 19:4097–4106
Wagner AD, Grothe W, Behl S (2005) Chemotherapy for advanced gastric cancer. Cochrane Library, issue 2, Oxford, England
Acknowledgments
The study was supported by Leading Academic Discipline Project of Shanghai Municipal Education Committee (J50208) and Shanghai Municipal Natural Science Foundation (No. 09ZR1417900). We thank the following investigators for supporting this meta-analysis by providing updated information on their studies (in alphabetical order): Dr Kohne CH, Klinikum Oldenburg, Germany; Dr Eduardo DR, Hospital Clínico San Carlos, Spain; Dr Cutsem EV, University Hospital Gasthuisberg, Belgium; Dr Skof E, Institute of Oncology, Slovenia; Dr Cassidy J, Glasgow University, Scotland; Dr Rothenberg ML, Vanderbilt-Ingram Cancer Center, USA; Dr Martoni AA, S. Orsola-Malpighi Hospital, Italy; Dr Comella P, National Tumour Institute, Italy; Dr Hoff PM, M.D. Anderson Cancer Center, USA; Dr Porschen R, Hospital Bremen, Germany.
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The authors declare that they have no competing interests.
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W. Ling and J. Fan are treated as co-first authors.
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Ling, W., Fan, J., Ma, Y. et al. Capecitabine-based chemotherapy for metastatic colorectal cancer. J Cancer Res Clin Oncol 137, 927–938 (2011). https://doi.org/10.1007/s00432-010-0954-0
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DOI: https://doi.org/10.1007/s00432-010-0954-0