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Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Capecitabine in the routine first-line treatment of elderly patients with advanced colorectal cancer - results from a non-interventional observation study

Authors: Alexander Stein, Julia Quidde, Jan Klaus Schröder, Thomas Göhler, Barbara Tschechne, Annette-Rosel Valdix, Heinz-Gert Höffkes, Silke Schirrmacher-Memmel, Tim Wohlfarth, Axel Hinke, Andreas Engelen, Dirk Arnold

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

The purpose of this observational study was to evaluate feasibility, efficacy results and toxicity observations of capecitabine in routine first line treatment of patients with metastatic colorectal cancer, with particular regard of elderly patients (>75 years of age).

Methods

Patients with colorectal cancer receiving capecitabine as part of their first-line treatment were recorded until detection of disease progression or up to a maximum of 12 cycles on standardized evaluation forms. Additional information on long-term outcomes, progression-free survival, and overall survival were retrieved at two follow-up time points. Obtained data were analyzed with regard to age up to 75 and >75 years of age. There were no specific requirements for patient selection and conduct of therapy, corresponding to the non-interventional nature of the study.

Results

In total, 1249 evaluable patients were enrolled in Germany. The median age of the study population was 74 years (range: 21–99). Capecitabine-based combination was administered in 56 % of patients in the overall population. The median treatment duration was about 5 months. Severe toxicities occurred rarely without any difference regarding age groups. The most common hematological toxicity was anemia. Gastrointestinal side effects and hand-food-syndrome (HFS) were the most frequent non-hematologic toxicities. Overall response rate (ORR) was significantly higher in the patient group <=75 years compared to patients >75 years of age (38 vs. 32 %, p=0.019). Median progression free survival (PFS 9.7 vs. 8.2 months, p=0.00021) and overall survival (OS 31.0 vs. 22.6 months, p<0.0001) was decreased in elderly patients.

Conclusion

Efficacy and tolerability of capecitabine treatment either as single drug or in various combination regimens, as proven in randomized studies, could be confirmed in a clinical routine setting. Patients older than 75 years may derive a relevant benefit by first line capecitabine-based treatment with good tolerability.
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Literature
1.
Schmoll HJ, Stein A. Colorectal cancer in 2013: Towards improved drugs, combinations and patient selection. Nat Rev Clin Oncol. 2014;11(2):79–80.CrossRefPubMed
2.
Van Cutsem E, Cervantes A, Nordlinger B, Arnold D, on behalf of the EGWG. Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-updagger. Ann Oncol. 2014;25 Suppl 3:iii1–9.CrossRefPubMed
3.
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(8):2282–92.PubMed
4.
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(21):4097–106.PubMed
5.
Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007;25(30):4779–86.CrossRefPubMed
6.
Arkenau HT, Arnold D, Cassidy J, Diaz-Rubio E, Douillard JY, Hochster H, et al. Efficacy of oxaliplatin plus capecitabine or infusional fluorouracil/leucovorin in patients with metastatic colorectal cancer: a pooled analysis of randomized trials. J Clin Oncol. 2008;26(36):5910–7.CrossRefPubMed
7.
Koopman M, Antonini NF, Douma J, Wals J, Honkoop AH, Erdkamp FL, et al. Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial. Lancet. 2007;370(9582):135–42.CrossRefPubMed
8.
Pectasides D, Papaxoinis G, Kalogeras K, Eleftheraki A, Xanthakis I, Makatsoris T, et al. XELIRI-bevacizumab versus FOLFIRI-bevacizumab as first-line treatment in patients with metastatic colorectal cancer: a Hellenic Cooperative Oncology Group phase III trial with collateral biomarker analysis. BMC Cancer. 2012;12(1):271.PubMedCentralCrossRefPubMed
9.
Tebbutt NC, Wilson K, Gebski VJ, Cummins MM, Zannino D, van Hazel GA, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol. 2010;28(19):3191–8.CrossRefPubMed
10.
Saltz LB, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008;26(12):2013–9.CrossRefPubMed
11.
Vasile E, Masi G, Fornaro L, Cupini S, Loupakis F, Bursi S, et al. A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer. Br J Cancer. 2009;100(11):1720–4.PubMedCentralCrossRefPubMed
12.
Di Bartolomeo M, Ciarlo A, Bertolini A, Barni S, Verusio C, Aitini E, et al. Capecitabine, oxaliplatin and irinotecan in combination, with bevacizumab (COI-B regimen) as first-line treatment of patients with advanced colorectal cancer. An Italian Trials of Medical Oncology phase II study. Eur J Cancer. 2015;51:473–81.CrossRefPubMed
13.
Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. OJ. 2001;L121:34–44.
14.
Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Ass. 1958;53:457–81.CrossRef
15.
Peto R, Peto J. Asymptotically efficient rank invariation test procedures (with discussion). J R Stat Soc A. 1972;135:185–206.CrossRef
16.
Cunningham D, Lang I, Marcuello E, Lorusso V, Ocvirk J, Shin DB, et al. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(11):1077–85.CrossRefPubMed
17.
Van Cutsem E, Hoff PM, Harper P, Bukowski RM, Cunningham D, Dufour P, et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from two large, randomised, phase III trials. Br J Cancer. 2004;90(6):1190–7.PubMedCentralCrossRefPubMed
18.
Heinemann V, von Weikersthal LF, Decker T, Kiani A, Vehling-Kaiser U, Al-Batran SE, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15(10):1065–75.CrossRefPubMed
19.
Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609–18.CrossRefPubMed
20.
Van Cutsem E, Rivera F, Berry S, Kretzschmar A, Michael M, DiBartolomeo M, et al. Safety and efficacy of first-line bevacizumab with FOLFOX, XELOX, FOLFIRI and fluoropyrimidines in metastatic colorectal cancer: the BEAT study. Ann Oncol. 2009;20(11):1842–7.CrossRefPubMed
21.
Kozloff M, Yood MU, Berlin J, Flynn PJ, Kabbinavar FF, Purdie DM, et al. Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer: the BRiTE observational cohort study. Oncologist. 2009;14(9):862–70.CrossRefPubMed
22.
Faron M, Pignon JP, Malka D, Bourredjem A, Douillard JY, Adenis A, et al. Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomised trials. Eur J Cancer. 2015;51(2):166–76.CrossRefPubMed
23.
Aparicio T. Bevacizumab + chemotherapy (BEV-CT) versus chemotherapy alone (CT) in elderly patients (pts) with untreated metastatic colorectal cancer (mCRC)—A randomized phase II trial. J Clin Oncol. 2015;33(15S):abstr. 3541.
24.
Yoshida M, Muro K, Tsuji A, Hamamoto Y, Yoshino T, Yoshida K, et al. Combination chemotherapy with bevacizumab and S-1 for elderly patients with metastatic colorectal cancer (BASIC trial). Eur J Cancer. 2015;51(8):935–41.CrossRefPubMed
25.
Comella P, Natale D, Farris A, Gambardella A, Maiorino L, Massidda B, et al. Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma: final results of the Southern Italy Cooperative Oncology Group Trial 0108. Cancer. 2005;104(2):282–9.CrossRefPubMed
26.
Feliu J, Escudero P, Llosa F, Bolanos M, Vicent JM, Yubero A, et al. Capecitabine as first-line treatment for patients older than 70 years with metastatic colorectal cancer: an oncopaz cooperative group study. J Clin Oncol. 2005;23(13):3104–11.CrossRefPubMed
27.
Feliu J, Salud A, Safont MJ, Garcia-Giron C, Aparicio J, Vera R, et al. First-line bevacizumab and capecitabine-oxaliplatin in elderly patients with mCRC: GEMCAD phase II BECOX study. Br J Cancer. 2014;111(2):241–8.PubMedCentralCrossRefPubMed
28.
McCleary NJ, Dotan E, Browner I. Refining the chemotherapy approach for older patients with colon cancer. J Clin Oncol. 2014;32(24):2570–80.CrossRefPubMed
29.
Seymour MT, Thompson LC, Wasan HS, Middleton G, Brewster AE, Shepherd SF, et al. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet. 2011;377(9779):1749–59.PubMedCentralCrossRefPubMed
30.
Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, Kohne CH, Rostoft S, Lemmens V, Mitry E et al: Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol 2015, 26(3):463-476.
31.
Twelves C, Scheithauer W, McKendrick J, Seitz JF, Van Hazel G, Wong A, et al. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012;23(5):1190–7.CrossRefPubMed
32.
Haller DG, O'Connell MJ, Cartwright TH, Twelves CJ, McKenna EF, Sun W, et al. Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials. Ann Oncol. 2015;26:715–24.CrossRefPubMed
33.
McCleary NJ, Meyerhardt JA, Green E, Yothers G, de Gramont A, Van Cutsem E, et al. Impact of Age on the Efficacy of Newer Adjuvant Therapies in Patients With Stage II/III Colon Cancer: Findings From the ACCENT Database. J Clin Oncol. 2013;31(20):2600–6.PubMedCentralCrossRefPubMed
34.
Haller D, O'Connell M. Impact of age and medical comorbidity (MC) on adjuvant treatment outcomes for stage III colon cancer (CC): A pooled analysis of individual patient data from four randomized controlled trials. J Clin Oncol. 2012;30:abstr. 3522.
35.
Kim ST, Hong YS, Lim HY, Lee J, Kim TW, Kim KP, et al. S-1 plus oxaliplatin versus capecitabine plus oxaliplatin for the first-line treatment of patients with metastatic colorectal cancer: updated results from a phase 3 trial. BMC Cancer. 2014;14:883.PubMedCentralCrossRefPubMed
36.
Yasui H, Muro K, Shimada Y, Tsuji A, Sameshima S, Baba H, et al. A phase 3 non-inferiority study of 5-FU/l-leucovorin/irinotecan (FOLFIRI) versus irinotecan/S-1 (IRIS) as second-line chemotherapy for metastatic colorectal cancer: updated results of the FIRIS study. J Cancer Res Clin Oncol. 2015;141(1):153–60.CrossRefPubMed
37.
Yoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, et al. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014;25(9):1743–9.PubMedCentralCrossRefPubMed
38.
Bajetta E, Di Bartolomeo M, Buzzoni R, Mariani L, Zilembo N, Ferrario E, et al. Uracil/ftorafur/leucovorin combined with irinotecan (TEGAFIRI) or oxaliplatin (TEGAFOX) as first-line treatment for metastatic colorectal cancer patients: results of randomised phase II study. Br J Cancer. 2007;96(3):439–44.PubMedCentralCrossRefPubMed
39.
Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH, Smith RE, et al. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006;24(13):2059–64.CrossRefPubMed
40.
Mizushima T, Tamagawa H, Matsuda C, Murata K, Fukunaga M, Ota H, et al. Phase II Study of Oral Tegafur/Uracil and Leucovorin plus Bevacizumab as a First-Line Therapy for Elderly Patients with Advanced or Metastatic Colorectal Cancer. Oncology. 2015;89(3):152–8.CrossRefPubMed
41.
Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909–19.CrossRefPubMed
42.
Cassidy J, Cox JV. Effective management of patients receiving XELOX: Evaluation of impact of dose modifications on outcome in patients from the NO16966, NO16967, and NO16968 trials. J Clin Oncol. 2011;29(supll 4):abstr. 497.
43.
Stintzing S, Fischer von Weikersthal L, Vehling-Kaiser U, Stauch M, Hass HG, Dietzfelbinger H, et al. Correlation of capecitabine-induced skin toxicity with treatment efficacy in patients with metastatic colorectal cancer: results from the German AIO KRK-0104 trial. Br J Cancer. 2011;105(2):206–11.PubMedCentralCrossRefPubMed
Metadata
Title
Capecitabine in the routine first-line treatment of elderly patients with advanced colorectal cancer - results from a non-interventional observation study
Authors
Alexander Stein
Julia Quidde
Jan Klaus Schröder
Thomas Göhler
Barbara Tschechne
Annette-Rosel Valdix
Heinz-Gert Höffkes
Silke Schirrmacher-Memmel
Tim Wohlfarth
Axel Hinke
Andreas Engelen
Dirk Arnold
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2113-8

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