This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Herrmann, R. Articles by Scheithauer, W. Search for Related Content PubMed PubMed Citation Articles by Herrmann, R. Articles by Scheithauer, W. Related Articles Related Correspondence Social Bookmarking                            What's this?

Gemcitabine Plus Capecitabine Compared With Gemcitabine Alone in Advanced Pancreatic Cancer: A Randomized, Multicenter, Phase III Trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group

Richard Herrmann, György Bodoky, Thomas Ruhstaller, Bengt Glimelius, Emilio Bajetta, Johannes Schüller, Piercarlo Saletti, Jean Bauer, Arie Figer, Bernhard Pestalozzi, Claus-Henning Köhne, Walter Mingrone, Salomon M. Stemmer, Karin Tàmas, Gabriela V. Kornek, Dieter Koeberle, Susanne Cina, Jürg Bernhard, Daniel Dietrich, Werner Scheithauer

From the University Hospital, Basel; Kantonsspital, St Gallen; Ospedale Regionale, Lugano; Centre Hospitalier Universitaire Vaudoise, Lausanne; Universitätsspital, Zurich; Kantonsspital, Aarau; Swiss Group for Clinical Cancer Research Coordinating Center, Bern, Switzerland; Szt László Hospital, Budapest, Hungary; University of Uppsala, Uppsala, Sweden; Istituto Nazionale per lo studio e la Cura dei Tumori, Milan, Italy; Krankenanstalt Rudolfstiftung, Wien; University of Vienna Medical School, Vienna, Austria; Sourasky Medical Center, Tel Aviv; Rabin Medical Center, Petach Tikva, Israel; and the Universitätsklinikum, Dresden, Germany

Address reprint requests to Richard Herrmann, MD, Division of Oncology, Department of Internal Medicine, University Hospital of Basel, Petersgraben 4, CH-4031 Basel, Switzerland; e-mail: herrmannr{at}uhbs.ch

Purpose This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer.

Patients and Methods Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m² twice daily on days 1 to 14 plus Gem 1,000 mg/m² by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m² by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Karnofsky performance score (KPS), presence of pain, and disease extent.

Results A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms.

Conclusion GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.

Supported by F. Hoffmann-La Roche AG, Eli Lilly Switzerland, and the Swiss federal government.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL, and the 13th Annual European Cancer Congress, October 31-November 3, 2005, Paris, France.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Correspondence

• Combination Chemotherapy in Advanced Pancreatic Cancer: Time to Raise the White Flag?
  Stephen A. Welch and Malcolm J. Moore
  JCO 2007 25: 2159-2161 [Full Text]

This article has been cited by other articles:

				D.-r. Xie, Q. Yang, D.-l. Chen, Z.-m. Jiang, Z.-f. Bi, W. Ma, and Y.-d. Zhang Gemcitabine-based Cytotoxic Doublets Chemotherapy for Advanced Pancreatic Cancer: Updated Subgroup Meta-analyses of Overall Survival Jpn. J. Clin. Oncol., February 10, 2010; (2010) hyp198v1. [Abstract] [Full Text] [PDF]

				M. H. Kulke, M. A. Tempero, D. Niedzwiecki, D. R. Hollis, H. L. Kindler, M. Cusnir, P. C. Enzinger, S. M. Gorsch, R. M. Goldberg, and R. J. Mayer Randomized Phase II Study of Gemcitabine Administered at a Fixed Dose Rate or in Combination With Cisplatin, Docetaxel, or Irinotecan in Patients With Metastatic Pancreatic Cancer: CALGB 89904 J. Clin. Oncol., November 20, 2009; 27(33): 5506 - 5512. [Abstract] [Full Text] [PDF]

				J. Tabernero and T. Macarulla Changing the Paradigm in Conducting Randomized Clinical Studies in Advanced Pancreatic Cancer: An Opportunity for Better Clinical Development J. Clin. Oncol., November 20, 2009; 27(33): 5487 - 5491. [Full Text] [PDF]

				D. Cunningham, I. Chau, D. D. Stocken, J. W. Valle, D. Smith, W. Steward, P. G. Harper, J. Dunn, C. Tudur-Smith, J. West, et al. Phase III Randomized Comparison of Gemcitabine Versus Gemcitabine Plus Capecitabine in Patients With Advanced Pancreatic Cancer J. Clin. Oncol., November 20, 2009; 27(33): 5513 - 5518. [Abstract] [Full Text] [PDF]

				T. UWAGAWA, P. J. CHIAO, T. GOCHO, S. HIROHARA, T. MISAWA, and K. YANAGA Combination Chemotherapy of Nafamostat Mesilate with Gemcitabine for Pancreatic Cancer Targeting NF-{kappa}B Activation Anticancer Res, August 1, 2009; 29(8): 3173 - 3178. [Abstract] [Full Text] [PDF]

				J. Matsubara, M. Ono, A. Negishi, H. Ueno, T. Okusaka, J. Furuse, K. Furuta, E. Sugiyama, Y. Saito, N. Kaniwa, et al. Identification of a Predictive Biomarker for Hematologic Toxicities of Gemcitabine J. Clin. Oncol., May 1, 2009; 27(13): 2261 - 2268. [Abstract] [Full Text] [PDF]

				A. MAMBRINI, P. PACETTI, A. DEL FREO, R. D. SETA, D. PEZZUOLO, T. TORRI, M. ORLANDI, R. TARTARINI, and M. CANTORE Gemcitabine-Capecitabine plus Intra-arterial Epirubicin-Cisplatin in Pretreated Pancreatic Cancer Patients: A Phase I Study Anticancer Res, May 1, 2009; 29(5): 1547 - 1549. [Abstract] [Full Text] [PDF]

				S. Cascinu, S. Jelic, and On behalf of the ESMO Guidelines Working Group Pancreatic cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann. Onc., May 1, 2009; 20(suppl_4): iv37 - iv40. [Full Text] [PDF]

				B. Freidlin and E. L. Korn Monitoring for Lack of Benefit: A Critical Component of a Randomized Clinical Trial J. Clin. Oncol., February 1, 2009; 27(4): 629 - 633. [Abstract] [Full Text] [PDF]

				B. M. Wolpin, A. F. Hezel, T. Abrams, L. S. Blaszkowsky, J. A. Meyerhardt, J. A. Chan, P. C. Enzinger, B. Allen, J. W. Clark, D. P. Ryan, et al. Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer J. Clin. Oncol., January 10, 2009; 27(2): 193 - 198. [Abstract] [Full Text] [PDF]

				M. K. Kim, K. H. Lee, B. I. Jang, T. N. Kim, J. R. Eun, S. H. Bae, H. M. Ryoo, S. A. Lee, and M. S. Hyun S-1 and Gemcitabine as an Outpatient-based Regimen in Patients with Advanced or Metastatic Pancreatic Cancer Jpn. J. Clin. Oncol., January 1, 2009; 39(1): 49 - 53. [Abstract] [Full Text] [PDF]

				T. Tanaka, M. Ikeda, T. Okusaka, H. Ueno, C. Morizane, A. Hagihara, S. Iwasa, and Y. Kojima Prognostic Factors in Japanese Patients with Advanced Pancreatic Cancer Treated with Single-agent Gemcitabine as First-line Therapy Jpn. J. Clin. Oncol., November 1, 2008; 38(11): 755 - 761. [Abstract] [Full Text] [PDF]

				M. A. Morgan, L. A. Parsels, J. Maybaum, and T. S. Lawrence Improving Gemcitabine-Mediated Radiosensitization Using Molecularly Targeted Therapy: A Review Clin. Cancer Res., November 1, 2008; 14(21): 6744 - 6750. [Abstract] [Full Text] [PDF]

				J. Bernhard, D. Dietrich, W. Scheithauer, D. Gerber, G. Bodoky, T. Ruhstaller, B. Glimelius, E. Bajetta, J. Schuller, P. Saletti, et al. Clinical Benefit and Quality of Life in Patients With Advanced Pancreatic Cancer Receiving Gemcitabine Plus Capecitabine Versus Gemcitabine Alone: A Randomized Multicenter Phase III Clinical Trial--SAKK 44/00-CECOG/PAN.1.3.001 J. Clin. Oncol., August 1, 2008; 26(22): 3695 - 3701. [Abstract] [Full Text] [PDF]

				D. Koeberle, P. Saletti, M. Borner, D. Gerber, D. Dietrich, C. B. Caspar, W. Mingrone, K. Beretta, F. Strasser, T. Ruhstaller, et al. Patient-Reported Outcomes of Patients With Advanced Biliary Tract Cancers Receiving Gemcitabine Plus Capecitabine: A Multicenter, Phase II Trial of the Swiss Group for Clinical Cancer Research J. Clin. Oncol., August 1, 2008; 26(22): 3702 - 3708. [Abstract] [Full Text] [PDF]

				Y. J. Chua and J. R. Zalcberg Pancreatic cancer--is the wall crumbling? Ann. Onc., July 1, 2008; 19(7): 1224 - 1230. [Abstract] [Full Text] [PDF]

				J. Nieto, M. L. Grossbard, and P. Kozuch Metastatic Pancreatic Cancer 2008: Is the Glass Less Empty? Oncologist, May 1, 2008; 13(5): 562 - 576. [Abstract] [Full Text] [PDF]

				K. Miyanishi, H. Ishiwatari, T. Hayashi, M. Takahashi, Y. Kawano, K. Takada, H. Ihara, T. Okuda, K. Takanashi, S. Takahashi, et al. A Phase I Trial of Arterial Infusion Chemotherapy with Gemcitabine and 5-Fluorouracil for Unresectable Advanced Pancreatic Cancer after Vascular Supply Distribution via Superselective Embolization Jpn. J. Clin. Oncol., April 1, 2008; 38(4): 268 - 274. [Abstract] [Full Text] [PDF]

				S. Boeck and V. Heinemann Second-Line Therapy in Gemcitabine-Pretreated Patients With Advanced Pancreatic Cancer J. Clin. Oncol., March 1, 2008; 26(7): 1178 - 1179. [Full Text] [PDF]

				S. Boeck, T. Hoehler, G. Seipelt, R. Mahlberg, A. Wein, A. Hochhaus, H.-P. Boeck, B. Schmid, E. Kettner, M. Stauch, et al. Capecitabine plus oxaliplatin (CapOx) versus capecitabine plus gemcitabine (CapGem) versus gemcitabine plus oxaliplatin (mGemOx): final results of a multicenter randomized phase II trial in advanced pancreatic cancer Ann. Onc., February 1, 2008; 19(2): 340 - 347. [Abstract] [Full Text] [PDF]

				M. H. Kulke, L. S. Blaszkowsky, D. P. Ryan, J. W. Clark, J. A. Meyerhardt, A. X. Zhu, P. C. Enzinger, E. L. Kwak, A. Muzikansky, C. Lawrence, et al. Capecitabine Plus Erlotinib in Gemcitabine-Refractory Advanced Pancreatic Cancer J. Clin. Oncol., October 20, 2007; 25(30): 4787 - 4792. [Abstract] [Full Text] [PDF]

				S. A. Welch and M. J. Moore Combination Chemotherapy in Advanced Pancreatic Cancer: Time to Raise the White Flag? J. Clin. Oncol., June 1, 2007; 25(16): 2159 - 2161. [Full Text] [PDF]