Observational study of adjuvant therapy with capecitabine in colon cancer

Abstract

Objective:

This observational study was conducted to document the safety of capecitabine-based adjuvant therapy in patients with resected colon cancer under routine clinical conditions.

Research and design methods:

ML20431 was a prospective, multicenter, non-interventional, observational study. It was designed to answer five research questions relating to safety, dosage and administration, and discontinuation from capecitabine-based adjuvant therapy. Patients were required to have R0 resected stage III colon cancer and have started treatment with capecitabine-based adjuvant therapy based on a decision by the investigator. Patients were followed over an observation period of ≤6 months after initiation of therapy. Investigators were required to complete the study case report form at study entry, each treatment cycle, and at the final examination.

Main outcome measures:

A total of 1485 patients were included in the study, and 1481 patients were treated with capecitabine and formed the analysis population. Most patients had colon cancer (78.3%), followed by rectal cancer (16.4%). Most patients had stage III disease (69.3%); the remaining patients had stage II disease (30.7%). The most common all-grade adverse reactions were hand–foot syndrome (46.9%), diarrhea (34.4%), and hemoglobin decreases (31.5%). Grade 3/4 adverse reactions were infrequent (<4%). Serious adverse events were reported in 96 patients (6.5%). Six or more cycles of treatment were completed by 77.9% of patients. Approximately two-thirds of patients (67.3%) received capecitabine monotherapy and the remainder (32.7%) received capecitabine in combination with ≥1 drugs, most commonly oxaliplatin (460 cases). Discontinuation of capecitabine was documented in 344 patients (23.2%). Study limitations: no efficacy data were collected; the questionnaires for patients’ expectations and satisfaction were not formally validated; and a few patients (<1.5%) had some retrospective data.

Conclusions:

The safety profile of capecitabine-based adjuvant therapy in a broad patient population with colon cancer is similar to that previously documented in phase III clinical trials.

Keywords: :

• Adjuvant chemotherapy
• Administration and dosage
• Capecitabine
• Colonic neoplasms
• Oxaliplatin
• Patient satisfaction
• Safety

Transparency

Declaration of funding

ML20431 was sponsored by Roche Pharma AG, Grenzach-Wyhlen, Germany.

Declaration of financial/other relationships

D.G. has disclosed that she has received grant funding and been on a speaker’s bureau for Roche Pharma AG. B.T. has disclosed that she has been a consultant/advisor for Roche, Amgen and Vifor Pharma. C.-C.S. has disclosed that he has been a consultant/advisor for Roche, Sanofi, Amgen, and GlaxoSmithKline. T.W. has disclosed that he is an employee of Roche and owns stock in the company. C.S., G.J., A.-R.V., P.S., R.H., and H.K. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

In addition to the investigators in the author list, we would like to acknowledge the following investigators who also participated in this study: U. Abt, Burladingen; K. Akrivakis, Hamburg; A. Ammon, Göttingen; H. Arzberger, Meiβen; M. Aβmann, Riesa; M. Becker, Porta Westfalica; M. Begemann, Hamburg; U. Behn, Haltern; R. Behrens, Halle (Saale); J. Behringer, Speyer; H. Berkermann, Eschwege; M. Bertram, Hamburg; M. Bischoff, Idar-Oberstein; K. Blumenstengel, Eisenach; B. Bohnsteen, Dessau; H. Bolouri, Kiel; D. Bosse, München; F. Breuer, Frechen; L. Brinkmann, Laatzen; U. Bückner, Bochum; K.-U. Däβler, Freital; L. Dietze, Köln; H. Dietzfelbinger, Herrsching; S. Dörfel, Dresden; H.-W. Dübbers, Ahaus; E. Eggers, Torgau; P. Ehscheidt, Neuwied; M. Eichstaedt, Düren; W. Elsel, Zwickau; H. Eschenburg, Güstrow; L. Fechner, Halle (Saale); H. Fiechtner, Stuttgart; T. Fietz, Singen; L. Fischer von Weikersthal, Amberg; U. Fleck, Luckenwalde; H. Forstbauer, Troisdorf; S. Frank-Gleich, Halle/Saale; S. Fries, Bamberg; S. Frühauf, Osnabrück; S. Fuxius, Heidelberg; S. Gebhard, Fulda; S. Gerhardt, Gera; J. Germeroth, Reichenbach; F. Gieseler, Kiel; T. Göhler, Dresden; M. Groschek, Würselen; M. Grundeis, Chemnitz; M. Grüner, Weiden; J. Haessner, Wolfsburg; L. Hahn, Herne; C. Hancken, Stade; D. Hartwigsen, Flensburg; H. Hass, Scheidegg; H. Hebart, Mutlangen; S. Hegewisch-Becker, Hamburg; P. Hegener-Tschochner, Düsseldorf; K. Heine, Wolfsburg; W. Heinz, Leonberg; M. Hensel, Mannheim; A. Herbrich, Dortmund; J. Heβling, Berlin; U. Hieber, Mannheim; C. Hinske, Würselen; M. Hoesl, Nürnberg; H.-G. Höffkes, Fulda; J. Hoffmann, Ludwigshafen; H.-J. Hurtz, Halle/Saale; U. Hutzschenreuter, Nordhorn; E. Höring, Stuttgart; H. Hülsheger, Peine; L. Jacobasch, Dresden; H.-P. Jungbluth, Neuwied; T. Kamp, Wendlingen; M. Karch, Simmern; J. Kern, Würzburg; M. Kindler, Berlin; D. Kingreen, Berlin; H. Kirchner, Hannover; A. Kirsch, Berlin; J. Kisro, Lübeck; M. Klein, Wiesbaden; J. Knoblich, Lörrach; Y.D. Ko, Bonn; U. Koch, Bad Soden; M. Koenigsmann, Hannover; A. Köhler, Langen; A. Kohlstedt, Zwickau; G. Kojouharoff, Darmstadt; S. Korsten, Bergisch Galdbach-Bensberg; S. Kremers, Lebach; W. Kühn, Berlin; I. Kühne, Weiβenfels; F. Kullmann, Weiden; K. Kürner, Gifhorn; F. Lange, Bonn; C. Lerchenmüller, Münster; R. Lipp, Hamburg; C. Longin, Berlin; S. Luft, Lehrte; B. Luhn, Hamburg; A. Lück, Rostock; C. Maas, Halberstadt; S. Mahlmann, Kaiserslautern; D. Mainka, Köln; C. Maintz, Würselen; F. Marquard, Celle; U. Martens, Heilbronn; B. Massner, Schriesheim; M. Matthias, Buckow; H. Messmann, Augsburg; D. Meyer, Göttingen; G. Michl, München; J. Mittermüller, Germering; E. Moorahrend, Porta Westfalica; S. Müller-Hagen, Hamburg; A. Ohmenhäuser, Böblingen; J. Ollech-Chwoyka, Ludwigslust; P. Panagiotou, Garbsen; J. Papke, Neustadt/Sachsen; V. Petersen, Heidenheim; B. Peuser, Leipzig; M. Plath, Augsburg; P. Porowski, Heilbronn; D. Pott, Bottrop; M. Pross, Berlin; L. Prügl, Zwiesel; G. Puchtler, Rosenheim; J. Rauh, Witten; C. Reddemann, Leverkusen; G. Reich, Berlin; M. Reiser, Köln; B. Rendenbach, Trier; D. Reschke, Oldenburg; F. Risse, Remagen; S. Rösel, Gütersloh; O. Rubanov, Hameln; K. Ruffert, Jena; U. Sauer, Nordhorn; T. Schanz, Chemnitz; M. Schauer, Nürnberg; U. Schellenberger, Wilhelmshaven; B. Scheuer, Pirmasens; R. Schlag, Würzburg; A. Schmidt, Cottbus; R. Schmits, Saarbrücken; J. Schmitz, Arnsberg; M. Schmitz, Mayen; U. Schneider, Berlin; B. Schöttker, Würzburg; D. Schröder, Hannover; J. Schröder, Mülheim; C. Schulz, Bad Kreuznach; M. Schulze, Zittau; M. Schwarz, Schöneck; A. Schwarzer, Leipzig; M. Schweigert, Berlin; C. Schweinitz, Gera; U. Schwinger, Stuttgart; K.-D. Schürer, Leipzig; S. Schütz, Bremerhaven; G. Seipelt, Bad Soden; J. Selbach, Duisburg; K. Sieg, Mülheim; U. Söling, Kassel; J. Spes, Altötting; C. Spohn, Halle; M. Stauch, Kronach; K. Stengele, Singen; N. Steudel, Halle (Saale); F. Strohbach, Berlin; P. Stübs, Magdeburg; I. Tamm, Berlin; H. Tanzer, Bad Reichenhall; M. Teich, Chemnitz; H. Tessen, Goslar; K. Tischbirek, Wiesbaden; G. Triebkorn, Weiβenfels; D. Tummes, Aachen; J. Uhlig, Naunhof; U. Vehling-Kaiser, Landshut; K. Verpoort, Hamburg; A. Völkl, München; M. von Staden, Hamburg; W. Weber, Homberg (Efze); R. Weinberg, Aachen; G. Weiβenborn, Twistringen; M. Welslau, Aschaffenburg; J. Wierecky, Hamburg; S. Wilhelm, Güstrow; F. Winkler, Laatzen; M. Wöhr, Plüderhausen; H. Wolf, Dresden; I. Wöllner, Mainz; J. Zimber, Nürnberg; K. Zuchold, Berlin.

Support for third-party writing assistance for this manuscript, provided by Miller Medical Communications, was funded by Roche Pharma AG.

Previous presentation: Presented in part at the European Society for Medical Oncology (ESMO) 13th World Congress on Gastrointestinal Cancer, 22–25 June 2011, Barcelona, Spain.