This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Moorsel, C. J.A. Articles by Pinedo, H. M. Search for Related Content PubMed Articles by van Moorsel, C. J.A. Articles by Pinedo, H. M.

Gemcitabine: Future Prospects of Single-Agent and Combination Studies

Department of Medical Oncology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

Correspondence: Godefridus J. Peters, Ph.D., Department of Medical Oncology, University Hospital Vrije Universiteit, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. Telephone: +31-20-444-2633; Fax: +31-20-444-3844.

ABSTRACT

Gemcitabine (2',2'-difluorodeoxycytidine, Gemzar) is a deoxycytidine analog with excellent antitumor activity against a number of solid tumors. Gemcitabine needs to be activated by deoxycytidine kinase and other kinases to its triphosphate, gemcitabine triphosphate, which can be incorporated into RNA and DNA. The latter effect is considered to be responsible for its antitumor effect and causes masked chain termination and inhibition of DNA repair. This effect may be of importance for combination with DNA interacting agents. In phase I trials daily, twice weekly, weekly and every two weeks schedules have been evaluated. At the weekly schedule of 1,000-1,250 mg/m² significant antitumor activity was observed in bladder, breast, ovary, and pancreatic cancer, non-small cell lung cancer (NSCLC), and small cell lung cancer of 31%, 33%, 22%, 11%, 22% and 27% total response rates, respectively. Gemcitabine also showed considerable improvement in clinical symptoms, while toxicity was not severe with mild myelosuppression. Due to its ability to inhibit DNA replication, combination studies were initiated with DNA damaging agents. For the various combinations with cisplatin in phase II studies on NSCLC, response rates varied from 42%-54%, with a median survival of generally more than 12 months. Also, combinations with taxanes, etoposide, doxorubicin and vindesin seem promising. Gemcitabine is an important agent for the management of several relatively chemoresistant cancer types, both with respect to antitumor activity and clinical benefit. Future research on combination studies deserves high priority considering the high response rates in NSCLC and bladder cancer.

Key Words. Gemcitabine • Cisplatin • Taxanes • Non-small cell lung cancer • Pancreatic cancer • Breast cancer • Antimetabolites • Deoxycytidine kinase

This article has been cited by other articles:

				S. A. Veltkamp, J. H. Beijnen, and J. H.M. Schellens Prolonged Versus Standard Gemcitabine Infusion: Translation of Molecular Pharmacology to New Treatment Strategy Oncologist, March 1, 2008; 13(3): 261 - 276. [Abstract] [Full Text] [PDF]

				T. Yeo, J Kintner, R Armand, R Perez, and L. Lewis Sublethal concentrations of gemcitabine (2',2'-difluorodeoxycytidine) alter mitochondrial ultrastructure and function without reducing mitochondrial DNA content in BxPC-3 human pancreatic carcinoma cells Human and Experimental Toxicology, December 1, 2007; 26(12): 911 - 921. [Abstract] [PDF]

				S. M. De Lange, C. J. van Groeningen, J. R. Kroep, A. Van Bochove, J. F. Snijders, G. J. Peters, H. M. Pinedo, and G. Giaccone Phase II trial of cisplatin and gemcitabine in patients with advanced gastric cancer Ann. Onc., March 1, 2004; 15(3): 484 - 488. [Abstract] [Full Text] [PDF]

				P. M. Fracasso, J. S. Rader, R. Govindan, T. J. Herzog, M. A. Arquette, A. Denes, D. G. Mutch, J. Picus, B. R. Tan, C. L. Fears, et al. Phase I study of rubitecan and gemcitabine in patients with advanced malignancies Ann. Onc., November 1, 2002; 13(11): 1819 - 1825. [Abstract] [Full Text] [PDF]

				J. R. Kroep, W. J. P. Loves, C. L. van der Wilt, E. Alvarez, I. Talianidis, E. Boven, B. J. M. Braakhuis, C. J. van Groeningen, H. M. Pinedo, and G. J. Peters Pretreatment Deoxycytidine Kinase Levels Predict in Vivo Gemcitabine Sensitivity Mol. Cancer Ther., April 1, 2002; 1(6): 371 - 376. [Abstract] [Full Text] [PDF]

				L. H. Einhorn, M. J. Stender, and S. D. Williams Phase II Trial of Gemcitabine in Refractory Germ Cell Tumors J. Clin. Oncol., February 1, 1999; 17(2): 509 - 509. [Abstract] [Full Text] [PDF]

				J. Wang, J. Neuhard, and S. Eriksson An Escherichia coli System Expressing Human Deoxyribonucleoside Salvage Enzymes for Evaluation of Potential Antiproliferative Nucleoside Analogs Antimicrob. Agents Chemother., October 1, 1998; 42(10): 2620 - 2625. [Abstract] [Full Text]