Journal of Clinical Oncology, Vol 13, 2731-2736, Copyright © 1995 by American Society of Clinical Oncology

ARTICLES

Advanced breast cancer: a phase II trial with gemcitabine

J Carmichael, K Possinger, P Phillip, M Beykirch, H Kerr, J Walling and AL Harris
Imperial Cancer Research Fund Clinical Oncology Unit, Churchill Hospital, Oxford, United Kingdom.

PURPOSE: In this phase II study, the efficacy and tolerability of gemcitabine were studied in 44 patients with locally advanced or metastatic breast cancer. PATIENTS AND METHODS: Of 40 patients assessable for response, 14 were chemotherapy-naive, seven had received adjuvant chemotherapy, and 19 had received one prior chemotherapy regimen for metastatic disease. Gemcitabine was administered as a 30- minute intravenous infusion once a week for 3 weeks followed by a 1- week rest every 4 weeks. The mean number of completed cycles administered was 2.7 and the mean dosage delivered was 725 mg/m2 per injection. Eighty-one percent of doses were delivered as scheduled. RESULTS: There were three complete responses and seven partial responses, for an overall response rate of 25.0% (95% confidence interval [CI], 12.7% to 41.2%). Four patients were not assessable for efficacy (one had insufficient therapy, two had no bidimensionally measurable disease, and one had neither). All responses were independently validated by an external oncology review board. Responses were observed early in treatment, with a median time to response of 1.9 months. The median survival duration for all 40 assessable patients was 11.5 months. Hematologic toxicity was generally mild, with World Health Organization (WHO) grade 3 and 4 leukopenia occurring in 6.8% and 2.3% of patients and neutropenia in 23.3% and 7.0%, of patients, respectively. The only other grade 4 toxicities were infection and nausea and vomiting in one patient each. One patient was withdrawn due to shortness of breath, possibly drug-related. Flu-like symptoms, which were mild, transient, and treatable with acetominophen, were reported in 6.8% of patients. Only one patient developed alopecia of severity greater than WHO grade 2. CONCLUSION: In view of the single-agent activity seen in advanced breast cancer, modest toxicity profile, and novel mechanism of action, gemcitabine deserves evaluation in breast cancer and is an ideal candidate for combination therapy.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. M. Ciruelos, J. Cortes, H. Cortes-Funes, J. I. Mayordomo, B. Bermejo, B. Ojeda, E. Garcia, C. A. Rodriguez, M. Munoz, P. Gomez, et al. Gemcitabine and capecitabine in previously anthracycline-treated metastatic breast cancer: a multicenter phase II study (SOLTI 0301 trial) Ann. Onc., November 25, 2009; (2009) mdp536v1. [Abstract] [Full Text] [PDF]

				H. K. Chew, J. H. Doroshow, P. Frankel, K. A. Margolin, G. Somlo, H.-J. Lenz, M. Gordon, W. Zhang, D. Yang, C. Russell, et al. Phase II Studies of Gemcitabine and Cisplatin in Heavily and Minimally Pretreated Metastatic Breast Cancer J. Clin. Oncol., May 1, 2009; 27(13): 2163 - 2169. [Abstract] [Full Text] [PDF]

				D. Mauri, N. P. Polyzos, G. Salanti, N. Pavlidis, and J. P. A. Ioannidis Multiple-Treatments Meta-analysis of Chemotherapy and Targeted Therapies in Advanced Breast Cancer J Natl Cancer Inst, December 17, 2008; 100(24): 1780 - 1791. [Abstract] [Full Text] [PDF]

				K. S. Albain, S. M. Nag, G. Calderillo-Ruiz, J. P. Jordaan, A. C. Llombart, A. Pluzanska, J. Rolski, A. S. Melemed, J. M. Reyes-Vidal, J. S. Sekhon, et al. Gemcitabine Plus Paclitaxel Versus Paclitaxel Monotherapy in Patients With Metastatic Breast Cancer and Prior Anthracycline Treatment J. Clin. Oncol., August 20, 2008; 26(24): 3950 - 3957. [Abstract] [Full Text] [PDF]

				Y. Ali, Y. Lin, M. M. Gharibo, M. K. Gounder, M. N. Stein, T. F. Lagattuta, M. J. Egorin, E. H. Rubin, and E. A. Poplin Phase I and Pharmacokinetic Study of Imatinib Mesylate (Gleevec) and Gemcitabine in Patients with Refractory Solid Tumors Clin. Cancer Res., October 1, 2007; 13(19): 5876 - 5882. [Abstract] [Full Text] [PDF]

				X.M. Li and F. Levi Circadian Physiology Is a Toxicity Target of the Anticancer Drug Gemcitabine in Mice J Biol Rhythms, April 1, 2007; 22(2): 159 - 166. [Abstract] [PDF]

				C. X. Ma, P. Steen, K. M. Rowland, R. D. Niedringhaus, T. R. Fitch, J. W. Kugler, D. W. Hillman, E. A. Perez, J. N. Ingle, and A. A. Adjei A phase II trial of a combination of pemetrexed and gemcitabine in patients with metastatic breast cancer: an NCCTG study Ann. Onc., February 1, 2006; 17(2): 226 - 231. [Abstract] [Full Text] [PDF]

				A. Hamilton and G. Hortobagyi Chemotherapy: What Progress in the Last 5 Years? J. Clin. Oncol., March 10, 2005; 23(8): 1760 - 1775. [Full Text] [PDF]

				H. S Sano, J A. Waddell, D. A Solimando Jr, P. Doulaveris, and R. Myhand Study of the effect of standardized chemotherapy order forms on prescribing errors and anti-emetic cost Journal of Oncology Pharmacy Practice, March 1, 2005; 11(1): 21 - 30. [Abstract] [PDF]

				M. D. Pegram, G. E. Konecny, C. O'Callaghan, M. Beryt, R. Pietras, and D. J. Slamon Rational Combinations of Trastuzumab With Chemotherapeutic Drugs Used in the Treatment of Breast Cancer J Natl Cancer Inst, May 19, 2004; 96(10): 739 - 749. [Abstract] [Full Text] [PDF]

				C. M. Rocha Lima, N. A. Rizvi, C. Zhang, J. E. Herndon 2nd, J. Crawford, R. Govindan, G. W. King, and M. R. Green Randomized phase II trial of gemcitabine plus irinotecan or docetaxel in stage IIIB or stage IV NSCLC Ann. Onc., March 1, 2004; 15(3): 410 - 418. [Abstract] [Full Text] [PDF]

				A. Alexopoulos, D. Tryfonopoulos, M. V. Karamouzis, G. Gerasimidis, I. Karydas, K. Kandilis, J. Stavrakakis, H. Stavrinides, C. Georganta, A. Ardavanis, et al. Evidence for in vivo synergism between docetaxel and gemcitabine in patients with metastatic breast cancer Ann. Onc., January 1, 2004; 15(1): 95 - 99. [Abstract] [Full Text] [PDF]

				E. Rivera, V. Valero, B. Arun, M. Royce, R. Adinin, K. Hoelzer, R. Walters, J. L. Wade III, L. Pusztai, and G. N. Hortobagyi Phase II Study of Pegylated Liposomal Doxorubicin in Combination With Gemcitabine in Patients With Metastatic Breast Cancer J. Clin. Oncol., September 1, 2003; 21(17): 3249 - 3254. [Abstract] [Full Text] [PDF]

				D. A. Rizzieri, V. K. Ibom, J. O. Moore, C. M. DeCastro, G. L. Rosner, D. J. Adams, T. Foster, N. Payne, M. Thompson, J. J. Vredenburgh, et al. Phase I Evaluation of Prolonged-infusion Gemcitabine with Fludarabine for Relapsed or Refractory Acute Myelogenous Leukemia Clin. Cancer Res., February 1, 2003; 9(2): 663 - 668. [Abstract] [Full Text] [PDF]

				J. O'Shaughnessy, C. Twelves, and M. Aapro Treatment for Anthracycline-Pretreated Metastatic Breast Cancer Oncologist, December 1, 2002; 7(90006): 4 - 12. [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]

				A. J. Bass, J. P. Gockerman, E. Hammett, C. M. DeCastro, D. J. Adams, G. L. Rosner, N. Payne, P. Davis, T. Foster, J. O. Moore, et al. Phase I Evaluation of Prolonged-Infusion Gemcitabine With Irinotecan for Relapsed or Refractory Leukemia or Lymphoma J. Clin. Oncol., July 1, 2002; 20(13): 2995 - 3000. [Abstract] [Full Text] [PDF]

				M. J. Egorin, E. G. Zuhowski, C. M. McCully, S. M. Blaney, J. Z. Kerr, S. L. Berg, and F. M. Balis Pharmacokinetics of Intrathecal Gemcitabine in Nonhuman Primates Clin. Cancer Res., July 1, 2002; 8(7): 2437 - 2442. [Abstract] [Full Text] [PDF]

				G. V. Kornek, K. Haider, W. Kwasny, M. Raderer, B. Schull, T. Payrits, D. Depisch, E. Kovats, F. Lang, and W. Scheithauer Treatment of Advanced Breast Cancer with Docetaxel and Gemcitabine with and without Human Granulocyte Colony-stimulating Factor Clin. Cancer Res., May 1, 2002; 8(5): 1051 - 1056. [Abstract] [Full Text] [PDF]

				D. A. Rizzieri, A. J. Bass, G. L. Rosner, J. P. Gockerman, C. M. DeCastro, W. P. Petros, D. J. Adams, M. J. Laughlin, P. Davis, T. Foster, et al. Phase I Evaluation of Prolonged-Infusion Gemcitabine With Mitoxantrone for Relapsed or Refractory Acute Leukemia J. Clin. Oncol., February 1, 2002; 20(3): 674 - 679. [Abstract] [Full Text] [PDF]

				F. J. Esteva, V. Valero, L. Pusztai, L. Boehnke-Michaud, A. U. Buzdar, and G. N. Hortobagyi Chemotherapy of Metastatic Breast Cancer: What to Expect in 2001 and Beyond Oncologist, April 1, 2001; 6(2): 133 - 146. [Abstract] [Full Text]

				E. Rivera, V. Valero, L. Syrewicz, Z. Rahman, F. L. Esteva, R. L. Theriault, M. M. Rosales, D. Booser, J. L. Murray, R. C. Bast Jr, et al. Phase I Study of Stealth Liposomal Doxorubicin in Combination With Gemcitabine in the Treatment of Patients With Metastatic Breast Cancer J. Clin. Oncol., March 15, 2001; 19(6): 1716 - 1722. [Abstract] [Full Text] [PDF]

				S. Okada, H. Ueno, T. Okusaka, M. Ikeda, J. Furuse, and Y. Maru Phase I Trial of Gemcitabine in Patients with Advanced Pancreatic Cancer Jpn. J. Clin. Oncol., January 1, 2001; 31(1): 7 - 12. [Abstract] [Full Text] [PDF]

				A. Patnaik, E. K. Rowinsky, B. K. Tammara, M. Hidalgo, R. L. Drengler, A. M. Garner, L. L. Siu, L. A. Hammond, S. A. Felton, S. Mallikaarjun, et al. Phase I and Pharmacokinetic Study of the Differentiating Agent Vesnarinone in Combination With Gemcitabine in Patients With Advanced Cancer J. Clin. Oncol., December 1, 2000; 18(23): 3974 - 3985. [Abstract] [Full Text] [PDF]

				G. Perez-Manga, A. Lluch, E. Alba, J. A. Moreno-Nogueira, M. Palomero, J. Garcia-Conde, D. Khayat, and N. Rivelles Gemcitabine in Combination With Doxorubicin in Advanced Breast Cancer: Final Results of a Phase II Pharmacokinetic Trial J. Clin. Oncol., July 1, 2000; 18(13): 2545 - 2552. [Abstract] [Full Text] [PDF]

				R. A. Nagourney, J. S. Link, J. B. Blitzer, C. Forsthoff, and S. S. Evans Gemcitabine Plus Cisplatin Repeating Doublet Therapy in Previously Treated, Relapsed Breast Cancer Patients J. Clin. Oncol., June 11, 2000; 18(11): 2245 - 2249. [Abstract] [Full Text] [PDF]

				L.-Y. Yang, L. Li, H. Jiang, Y. Shen, and W. Plunkett Expression of ERCC1 Antisense RNA Abrogates Gemcitabine-mediated Cytotoxic Synergism with Cisplatin in Human Colon Tumor Cells Defective in Mismatch Repair but Proficient in Nucleotide Excision Repair Clin. Cancer Res., March 1, 2000; 6(3): 773 - 781. [Abstract] [Full Text]

				C. Bokemeyer, A. Gerl, P. Schoffski, A. Harstrick, N. Niederle, J. Beyer, J. Casper, H.J. Schmoll, and L. Kanz Gemcitabine in Patients With Relapsed or Cisplatin-Refractory Testicular Cancer J. Clin. Oncol., February 1, 1999; 17(2): 512 - 512. [Abstract] [Full Text] [PDF]

				C. L. Vogel and J.-M. Nabholtz Monotherapy of Metastatic Breast Cancer: A Review of Newer Agents Oncologist, February 1, 1999; 4(1): 17 - 33. [Abstract] [Full Text]

				G. N. Hortobagyi Treatment of Breast Cancer N. Engl. J. Med., October 1, 1998; 339(14): 974 - 984. [Full Text] [PDF]