Annals of Oncology Advance Access originally published online on August 8, 2005
Annals of Oncology 2005 16(10):1639-1645; doi:10.1093/annonc/mdi309
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2005 European Society for Medical Oncology
A phase III trial of pemetrexed plus gemcitabine versus gemcitabine in patients with unresectable or metastatic pancreatic cancer
1 University of Berlin, Berlin, Germany; 2 Tyler Cancer Center, Tyler, TX; 3 University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 4 Erasme University Hospital, Brussels; 5 University Hospital Ghent, Ghent, Belgium; 6 Hospital Bogenhausen, Munich, Germany; 7 Eli Lilly and Company, Indianapolis, IN; 8 US Oncology, Houston, TX; 9 University of Chicago, Chicago, IL, USA
* Correspondence to: Dr H. Oettle, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Medizinische Klinik mit Schwerpunkt Hämatologie/Onkologie, Augustenburger Platz 1, Berlin, D-13353, Germany. Tel: +49-30-4505-53222, Fax: +49-30-4505-53959. E-mail: helmut.oettle{at}charite.de
Background: This randomized phase III study compared the overall survival (OS) of pemetrexed plus gemcitabine (PG) versus standard gemcitabine (G) in patients with advanced pancreatic cancer.
Patients and methods: Patients with unresectable locally advanced or metastatic pancreatic cancer and no prior systemic therapy (including 5-fluorouracil as a radiosensitizer) were randomized to receive either 1250 mg/m2 gemcitabine on days 1 and 8 plus pemetrexed 500 mg/m2 after gemcitabine on day 8 (PG arm) of each 21-day cycle, or gemcitabine 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle (G arm).
Results: Five hundred and sixty-five patients with well-balanced baseline characteristics were randomly assigned (283 PG, 282 G). OS was not improved on the PG arm (6.2 months) compared with the G arm (6.3 months) (P = 0.8477). Progression-free survival (3.9 versus 3.3 months; P = 0.1109) and time to treatment failure (3 versus 2.2 months; P = 0.2680) results were similar. Tumor response rate (14.8% versus 7.1%; P = 0.004) was significantly better on the PG arm. Grade 3 or 4 neutropenia (45.1% versus 12.8%), thrombocytopenia (17.9% versus 6.2%), anemia (13.9% versus 2.9%), febrile neutropenia (9.9% versus 0.4%; all P <0.001) and fatigue (15% versus 6.6%; P = 0.002) were significantly more common on the PG arm. Four treatment-related deaths occurred on the PG arm and none in the G arm.
Conclusions: Pemetrexed plus gemcitabine therapy did not improve OS. Single-agent gemcitabine remains the standard of care for advanced pancreatic cancer.
Key words: gemcitabine, pancreatic cancer, pemetrexed, phase III, survival
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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. L. Hensley, J. Larkin, M. Fury, S. Gerst, D. F. Tai, P. Sabbatini, J. Konner, M. Orlando, T. L. Goss, and C. A. Aghajanian A Phase I Trial of Pemetrexed Plus Gemcitabine Given Biweekly with B-Vitamin Support in Solid Tumor Malignancies or Advanced Epithelial Ovarian Cancer Clin. Cancer Res., October 1, 2008; 14(19): 6310 - 6316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Pino, M. Balsamo, F. Di Modugno, M. Mottolese, M. Alessio, E. Melucci, M. Milella, D. J. McConkey, U. Philippar, F. B. Gertler, et al. Human Mena+11a Isoform Serves as a Marker of Epithelial Phenotype and Sensitivity to Epidermal Growth Factor Receptor Inhibition in Human Pancreatic Cancer Cell Lines Clin. Cancer Res., August 1, 2008; 14(15): 4943 - 4950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R. Simon, C. F. Verschraegen, P. A. Janne, C. J. Langer, A. Dowlati, S. M. Gadgeel, K. Kelly, G. P. Kalemkerian, A. M. Traynor, G. Peng, et al. Pemetrexed Plus Gemcitabine As First-Line Chemotherapy for Patients With Peritoneal Mesothelioma: Final Report of a Phase II Trial J. Clin. Oncol., July 20, 2008; 26(21): 3567 - 3572. [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]
|
|
|
|
|
|
D. Laheru, E. Lutz, J. Burke, B. Biedrzycki, S. Solt, B. Onners, I. Tartakovsky, J. Nemunaitis, D. Le, E. Sugar, et al. Allogeneic Granulocyte Macrophage Colony-Stimulating Factor-Secreting Tumor Immunotherapy Alone or in Sequence with Cyclophosphamide for Metastatic Pancreatic Cancer: A Pilot Study of Safety, Feasibility, and Immune Activation Clin. Cancer Res., March 1, 2008; 14(5): 1455 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Burris III and C. Rocha-Lima New Therapeutic Directions for Advanced Pancreatic Cancer: Targeting the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways Oncologist, March 1, 2008; 13(3): 289 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Heinemann, R. Labianca, A. Hinke, and C. Louvet Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study Ann. Onc., October 1, 2007; 18(10): 1652 - 1659. [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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. J. Moore, D. Goldstein, J. Hamm, A. Figer, J. R. Hecht, S. Gallinger, H. J. Au, P. Murawa, D. Walde, R. A. Wolff, et al. Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group J. Clin. Oncol., May 20, 2007; 25(15): 1960 - 1966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Van Cutsem, C. Verslype, and P. A. Grusenmeyer Lessons Learned in the Management of Advanced Pancreatic Cancer J. Clin. Oncol., May 20, 2007; 25(15): 1949 - 1952. [Full Text] [PDF]
|
|
|
|
|
|
S Boeck, K Weigang-Kohler, M Fuchs, E Kettner, D Quietzsch, J Trojan, O Stotzer, S Zeuzem, F Lordick, C-H Kohne, et al. Second-line chemotherapy with pemetrexed after gemcitabine failure in patients with advanced pancreatic cancer: a multicenter phase II trial Ann. Onc., April 1, 2007; 18(4): 745 - 751. [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]
|
|
|
|
 |
|
 S. Chattopadhyay, R. G. Moran, and I. D. Goldman Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applications Mol. Cancer Ther., February 1, 2007; 6(2): 404 - 417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. K. Abou-Alfa, R. Letourneau, G. Harker, M. Modiano, H. Hurwitz, N. S. Tchekmedyian, K. Feit, J. Ackerman, R. L. De Jager, S. G. Eckhardt, et al. Randomized Phase III Study of Exatecan and Gemcitabine Compared With Gemcitabine Alone in Untreated Advanced Pancreatic Cancer J. Clin. Oncol., September 20, 2006; 24(27): 4441 - 4447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Richards, K. A. Boehm, D. M. Waterhouse, D. J. Wagener, S. S. Krishnamurthi, A. Rosemurgy, W. Grove, K. Macdonald, S. Gulyas, M. Clark, et al. Gemcitabine plus CI-994 offers no advantage over gemcitabine alone in the treatment of patients with advanced pancreatic cancer: results of a phase II randomized, double-blind, placebo-controlled, multicenter study Ann. Onc., July 1, 2006; 17(7): 1096 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. S. P. Rocha Lima and A. M. Flores Gemcitabine Doublets in Advanced Pancreatic Cancer: Should We Move On? J. Clin. Oncol., January 20, 2006; 24(3): 327 - 329. [Full Text] [PDF]
|
|