Annals of Oncology 14:97-104, 2003
© 2003 European Society for Medical Oncology
Original Paper |
Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial
1 Division of Oncology, Department of Internal Medicine I, Vienna University Medical School, Vienna; 2 Department of Surgery, Wiener Neustadt General Hospital, Wiener Neustadt; 3 Department of Internal Medicine, Kirchdorf General Hospital, Kirchdorf a.d. Krems; 4 Department of Surgery, Neunkirchen General Hospital, Neunkirchen, Austria
Received 27 May 2002; revised 9 August 2002; accepted 9 September 2002
Background:
Gemcitabine is an active antitumor agent in the treatment of advanced pancreatic cancer, and has shown potential synergistic activity with the oral fluoropyrimidine capecitabine in previous phase I/II trials. Based on this background and in order to define the therapeutic potential and tolerance of this combination more precisely, the present randomized multicenter phase II trial was initiated.
Patients and methods:
We prospectively randomized 83 patients to treatment with biweekly gemcitabine 2200 mg/m2 given as a 30 min intravenous infusion on day 1, or the same treatment plus oral capecitabine 2500 mg/m2 given from days 1 to 7. In both arms, chemotherapy was administered for a duration of 6 months unless there was prior evidence of progressive disease. The efficacy of the two treatment arms was evaluated according to standard criteria, i.e. objective response, progression-free survival (PFS) and overall survival (OS), as well as by analysis of clinical benefit response.
Results:
The overall objective response rate among the 42 patients treated with gemcitabine alone was 14% compared with 7/41 (17%) among those treated with the combination arm. Similar to response rates, there was no apparent difference between the two groups in terms of median PFS (4.0 versus 5.1 months) and median OS (8.2 versus 9.5 months) in the gemcitabine and combination arm, respectively. Of 61 patients with tumor-related symptoms, who were considered evaluable for clinical benefit response, 10/30 (33%) and 15/31 (48.4%) experienced significant palliation in the gemcitabine and combination arm, respectively. Chemotherapy was well tolerated in both arms with only four versus six patients experiencing WHO grade 3 symptoms. Apart from the occurrence of hand–foot syndrome in 10 patients, no major increase in incidence and/or degree of adverse reactions was noted in the combination arm.
Conclusions:
Results of this trial suggest a fairly good therapeutic index for the combination of biweekly high-dose gemcitabine and capecitabine for the treatment of advanced pancreatic cancer. Despite a somewhat superior clinical benefit response rate, no advantage over single-agent gemcitabine, however, was noted in terms of objective efficacy parameters.
Key words: capecitabine, chemotherapy, gemcitabine, pancreatic cancer
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 G. Palmieri, G. Merola, P. Federico, L. Petillo, M. Marino, M. Lalle, M. Milella, A. Ceribelli, L. Montella, C. Merola, et al. Preliminary results of phase II study of capecitabine and gemcitabine (CAP-GEM) in patients with metastatic pretreated thymic epithelial tumors (TETs) Ann. Onc., October 30, 2009; (2009) mdp483v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Traina, M. Theodoulou, K. Feigin, S. Patil, K. L. Tan, C. Edwards, U. Dugan, L. Norton, and C. Hudis Phase I Study of a Novel Capecitabine Schedule Based on the Norton-Simon Mathematical Model in Patients With Metastatic Breast Cancer J. Clin. Oncol., April 10, 2008; 26(11): 1797 - 1802. [Abstract] [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]
|
|
|
|
|
|
A. Sultana, C. T. Smith, D. Cunningham, N. Starling, J. P. Neoptolemos, and P. Ghaneh Meta-Analyses of Chemotherapy for Locally Advanced and Metastatic Pancreatic Cancer J. Clin. Oncol., June 20, 2007; 25(18): 2607 - 2615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Herrmann, G. Bodoky, T. Ruhstaller, B. Glimelius, E. Bajetta, J. Schuller, P. Saletti, J. Bauer, A. Figer, B. Pestalozzi, et al. 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 J. Clin. Oncol., June 1, 2007; 25(16): 2212 - 2217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Taieb, T Lecomte, T Aparicio, A Asnacios, T Mansourbakht, P Artru, D Fallik, J. Spano, B Landi, G Lledo, et al. FOLFIRI.3, a new regimen combining 5-fluorouracil, folinic acid and irinotecan, for advanced pancreatic cancer: results of an Association des Gastro-Enterologues Oncologues (Gastroenterologist Oncologist Association) multicenter phase II study Ann. Onc., March 1, 2007; 18(3): 498 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Xiros, P. Papacostas, T. Economopoulos, G. Samelis, E. Efstathiou, E. Kastritis, H. Kalofonos, A. Onyenadum, D. Skarlos, A. Bamias, et al. Carboplatin plus gemcitabine in patients with inoperable or metastatic pancreatic cancer: a phase II multicenter study by the Hellenic Cooperative Oncology Group Ann. Onc., May 1, 2005; 16(5): 773 - 779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Conroy, B. Paillot, E. Francois, R. Bugat, J.-H. Jacob, U. Stein, S. Nasca, J.-P. Metges, O. Rixe, P. Michel, et al. Irinotecan Plus Oxaliplatin and Leucovorin-Modulated Fluorouracil in Advanced Pancreatic Cancer--A Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer Study J. Clin. Oncol., February 20, 2005; 23(6): 1228 - 1236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Stathopoulos, K. Syrigos, A. Polyzos, G. Fountzilas, S. K. Rigatos, N. Ziras, A. Potamiannou, I. Tsiakopoulos, N. Androulakis, G. Aravantinos, et al. Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study Ann. Onc., February 1, 2004; 15(2): 224 - 229. [Abstract] [Full Text] [PDF]
|
|