Gallbladder Cancer Medication

  • Author: Mary Denshaw-Burke, MD, FACP; Chief Editor: Jules E Harris, MD   more...
 
Updated: Apr 23, 2012
 

Medication Summary

Historically, chemotherapy has not shown significant activity in gallbladder carcinoma. Typically, 5-fluorouracil (5-FU) has been used with response rates of 10-24% in advanced disease. Often 5-FU is administered either as a bolus or as a prolonged infusion regimen with radiation. Capecitabine is a currently available oral alternative to a prolonged 5-FU infusion.

More recently, gemcitabine has shown activity in gallbladder cancer. Early phase studies show an increased response rate with gemcitabine combination therapy over historical treatment response rates with 5-FU alone. Gemcitabine has been studied in combination with cis-platinum and capecitabine.

Currently, no clearly defined standard exists for chemotherapy in gallbladder cancer. Patients should be encouraged to participate in clinical trials.

Next

Antineoplastic agents

Class Summary

These agents inhibit cell growth and proliferation.

View full drug information

Gemcitabine (Gemzar)

 

Cytidine analog, after intracellular metabolism to active nucleotide, inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA. Cell cycle-specific for S phase.

This drug has been shown to have activity in a phase-2 trial against relapsed germ cell tumors.

View full drug information

Cisplatin (Platinol)

 

Platinum-containing compound that exerts antineoplastic effect by covalently binding to DNA with preferential binding to N-7 position of guanine and adenosine. Can react with 2 different sites on DNA to cause cross-links. Platinum complex also can bind to nucleus and cytoplasmic protein. A bifunctional alkylating agent, once activated to aquated form in cell, binds to DNA, resulting in interstrand and intrastrand cross-linking and denaturation of double helix.

Modify dose on basis of CrCl. Avoid use if CrCl < 60 mL/min.

View full drug information

Capecitabine (Xeloda)

 

Prodrug of fluorouracil that undergoes hydrolysis in liver and tissues to form the active moiety (fluorouracil), inhibiting thymidylate synthetase, which in turn blocks methylation of deoxyuridylic acid to thymidylic acid. This step interferes with DNA, and to a lesser degree with RNA synthesis.

Previous
Proceed to Follow-up
 
 
Contributor Information and Disclosures
Author

Mary Denshaw-Burke, MD, FACP  Clinical Assistant Professor of Medicine, Jefferson Medical College of Thomas Jefferson University; Clinical Assistant Professor, Affiliated Clinical Faculty of the Lankenau Institute for Medical Research; Program Director of Hematology/Oncology Fellowship, Education Coordinator for Oncology, Lankenau Medical Center

Mary Denshaw-Burke, MD, FACP is a member of the following medical societies: American College of Physicians and Pennsylvania Medical Society

Disclosure: Novartis Pharmaceuticals Honoraria Speaking and teaching

Coauthor(s)

Jessica B Katz, MD, PhD, FACP  Associate Director, Discovery Medicine Clinical Pharmacology, Oncology Division, Bristol Myers Squibb

Jessica B Katz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, and Phi Beta Kappa

Disclosure: BMS Salary Employment

Andrew Scott Kennedy, MD  Co-Medical Director, Wake Radiology Oncology

Andrew Scott Kennedy, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Hepato-Pancreato-Biliary Association, American Society for Therapeutic Radiology and Oncology, American Society of Clinical Oncology, and Radiological Society of North America

Disclosure: Nothing to disclose.

Specialty Editor Board

Michael Perry, MD, MS, MACP  Nellie B Smith Chair of Oncology Emeritus, Director, Division of Hematology and Medical Oncology, Deputy Director, Ellis Fischel Cancer Center, University of Missouri-Columbia School of Medicine

Michael Perry, MD, MS, MACP is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society of Clinical Oncology, American Society of Hematology, International Association for the Study of Lung Cancer, and Missouri State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Benjamin Movsas, MD  Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

References

  1. National Cancer Institute. Cancer Statistics. SEER Surveillance, Epidemiology, and End Results. Available at http://seer.cancer.gov/. Accessed 2008.

  2. Schottenfeld D and Fraumeni J. Cancer. Epidemiology and Prevention. 3rd. Oxford University Press; 2006:787-800.

  3. Lowenfels AB, Maisonneuve P, Boyle P, Zatonski WA. Epidemiology of gallbladder cancer. Hepatogastroenterology. May-Jun 1999;46(27):1529-32. [Medline].

  4. Bernstein CN, Blanchard JF, Kliewer E, Wajda A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer. Feb 15 2001;91(4):854-62. [Medline].

  5. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J Cancer. Apr 1 2006;118(7):1591-602. [Medline].

  6. Matsukura N, Yokomuro S, Yamada S, Tajiri T, Sundo T, Hadama T, et al. Association between Helicobacter bilis in bile and biliary tract malignancies: H. bilis in bile from Japanese and Thai patients with benign and malignant diseases in the biliary tract. Jpn J Cancer Res. Jul 2002;93(7):842-7. [Medline].

  7. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. Apr 24 2003;348(17):1625-38. [Medline].

  8. Tsuchiya Y, Sato T, Kiyohara C, Yoshida K, Ogoshi K, Nakamura K. Genetic polymorphisms of cytochrome P450 1A1 and risk of gallbladder cancer. J Exp Clin Cancer Res. Mar 2002;21(1):119-24. [Medline].

  9. Singh MK, Pandey UB, Ghoshal UC, Srivenu I, Kapoor VK, Choudhuri G. Apolipoprotein B-100 XbaI gene polymorphism in gallbladder cancer. Hum Genet. Feb 2004;114(3):280-3. [Medline].

  10. Wu LC, Chen LT, Tsai YJ, Lin CM, Lin CY, Tian YF, et al. Alpha-methylacyl coenzyme A racemase overexpression in gallbladder carcinoma confers an independent prognostic indicator. J Clin Pathol. Apr 2012;65(4):309-14. [Medline].

  11. Benjamin IS. Biliary cystic disease: the risk of cancer. J Hepatobiliary Pancreat Surg. 2003;10(5):335-9. [Medline].

  12. Hu B, Gong B, Zhou DY. Association of anomalous pancreaticobiliary ductal junction with gallbladder carcinoma in Chinese patients: an ERCP study. Gastrointest Endosc. Apr 2003;57(4):541-5. [Medline].

  13. American Cancer Society. Key Statistics for Gallbladder Cancer. Available at http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_are_the_key_statistics_for_gall_bladder_cancer_68.asp?sitearea=.. Accessed March 29, 2008.

  14. American Joint Committee on Cancer. Staging Resources. AJCC Staging Resources. Available at http://www.cancerstaging.org/staging/index.html. Accessed 2008.

  15. Mohandas KM, Swaroop VS, Gullar SU, Dave UR, Jagannath P, DeSouza LJ. Diagnosis of malignant obstructive jaundice by bile cytology: results improved by dilating the bile duct strictures. Gastrointest Endosc. Mar-Apr 1994;40(2 Pt 1):150-4. [Medline].

  16. Gupta P, Chitalkar P, Sen A, et al. Combination of gemcite and cisplatin chemotherapy in unresectable gallbladder cancer. J Clin Oncol. ASCO Annual Meeting Proceedings (Post-Meeting Edition). 2007;25, No18s (June 20 Supplement):15166.

  17. Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: a randomized controlled study. J Clin Oncol. Oct 20 2010;28(30):4581-6. [Medline].

  18. Valle JS, Wasan HS, Palmer DD, et al. Gemcitabine with or without cisplatin in patients (pts) with advanced or metastatic biliary tract cancer (ABC): Results of a multicenter, randomized phase III trial (the UK ABC-02 trial). J Clin Oncol. (suppl; abstr 4503) 2009;27:15s. [Full Text].

  19. Iqbal S, Rankin C, Lenz HJ, et al. A phase II trial of gemcitabine and capecitabine in patients with unresectable or metastatic gallbladder cancer or cholangiocarcinoma: Southwest Oncology Group study S0202. Cancer Chemother Pharmacol. Dec 2011;68(6):1595-602. [Medline].

  20. Malka D, Trarbach T, Fartoux L, et al. A multicenter, randomized phase II trial of gemcitabine and oxaliplatin (GEMOX) alone or in combination with biweekly cetuximab in the first-line treatment of advanced biliary cancer: interim analysis of the BINGO trial. J Clin Oncol. 2009;27(15 Suppl):Abstr 4520.

  21. Gruenberger B, Schueller J, Heubrandtner U, et al. Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study. Lancet Oncol. Dec 2010;11(12):1142-8. [Medline].

  22. Gallardo J, Rubio B, Ahumada M, et al. Therapy for advanced gallbladder cancer: Improving survival. J Clin Oncol. (May 20 suppl; abstr 15566) 2008;26:[Full Text].

  23. Dixon E, Vollmer CM Jr, Sahajpal A, et al. An aggressive surgical approach leads to improved survival in patients with gallbladder cancer: a 12-year study at a North American Center. Ann Surg. Mar 2005;241(3):385-94. [Medline]. [Full Text].

  24. Ito H, Ito K, D'Angelica M, Gonen M, Klimstra D, Allen P. Accurate staging for gallbladder cancer: implications for surgical therapy and pathological assessment. Ann Surg. Aug 2011;254(2):320-5. [Medline].

  25. Jensen EH, Abraham A, Jarosek S, Habermann EB, Al-Refaie WB, Vickers SA, et al. Lymph node evaluation is associated with improved survival after surgery for early stage gallbladder cancer. Surgery. Oct 2009;146(4):706-11; discussion 711-3. [Medline].

  26. Abdalla EK, Vauthey JN. Biliary tract cancer. Curr Opin Gastroenterol. Sep 2001;17(5):450-7. [Medline].

  27. American Cancer Society. Facts and Figures. Available at www.cancer.org/docroot/stt/stt_0.asp.. Accessed March 29, 2008.

  28. Bartlett DL, Ramanathan RK, Ben-Josef E. Cancer of the Biliary Tree. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008:1156-86.

  29. Benson AB, Curley SA, Langnas AN. Hepatobiliary Cancers. NCCN Clinical Practice Guidelines in Oncology. 2005;1.

  30. Chang BB, Thomas MB, Wolff RA. Pancreatic Cancer and Hepatobiliary Malignancies. In: Kantarjian HM, Wolff RA, Koller CA. MD Anderson Manual of Medical Oncology. 2nd ed. New York, NY: McGraw-Hill Medical Publishing Division; 2006:383-393.

  31. Czito BG, Hurwitz HI, Clough RW, Tyler DS, Morse MA, Clary BM. Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience. Int J Radiat Oncol Biol Phys. Jul 15 2005;62(4):1030-4. [Medline].

  32. Dawes LG. Gallbladder cancer. Cancer Treat Res. 2001;109:145-55. [Medline].

  33. Dingle BH, Rumble RB, Brouwers MC,. The role of gemcitabine in the treatment of cholangiocarcinoma and gallbladder cancer: a systematic review. Can J Gastroenterol. Dec 2005;19(12):711-6. [Medline].

  34. Douglas HO, Tepper JE, Leichman L. Neoplasms of the Gallbladder. In: Holland JF, et al, eds. Cancer Medicine. 3rd ed. Philadelphia, Pa: Lea & Febiger; 1993:1448-1454.

  35. Doval DC, Sekhon JS, Gupta SK, Fuloria J, Shukla VK, Gupta S. A phase II study of gemcitabine and cisplatin in chemotherapy-naive, unresectable gall bladder cancer. Br J Cancer. Apr 19 2004;90(8):1516-20. [Medline].

  36. Gallardo JO, Rubio B, Fodor M, Orlandi L, Yanez M, Gamargo C. A phase II study of gemcitabine in gallbladder carcinoma. Ann Oncol. Oct 2001;12(10):1403-6. [Medline].

  37. Gunderson LL, Haddock MG, Foo ML, Todoroki T, Nagorney D. Conformal irradiation for hepatobiliary malignancies. Ann Oncol. 1999;10 Suppl 4:221-5. [Medline].

  38. Gunderson LL, Willett CG. Pancreas and Hepatobiliary Tract. In: Perez CA, Brady LW, eds. Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1997:1467-1488.

  39. Hawkins WG, DeMatteo RP, Jarnagin WR, Ben-Porat L, Blumgart LH, Fong Y. Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. Mar 2004;11(3):310-5. [Medline].

  40. Houry S, Haccart V, Huguier M, Schlienger M. Gallbladder cancer: role of radiation therapy. Hepatogastroenterology. May-Jun 1999;46(27):1578-84. [Medline].

  41. Ito H, Matros E, Brooks DC, Osteen RT, Zinner MJ, Swanson RS, et al. Treatment outcomes associated with surgery for gallbladder cancer: a 20-year experience. J Gastrointest Surg. Feb 2004;8(2):183-90. [Medline].

  42. Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. Apr 1 2005;23(10):2332-8. [Medline].

  43. Knox JJ, Hedley D, Oza A, Feld R, Siu LL, Chen E. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. Apr 1 2005;23(10):2332-8. [Medline].

  44. Kresl JJ, Schild SE, Henning GT, Gunderson LL, Donohue J, Pitot H. Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma. Int J Radiat Oncol Biol Phys. Jan 1 2002;52(1):167-75. [Medline].

  45. Lillemoe K, Kennedy AS, Picus J. Clinical Management of Carcinoma of the Biliary Tree. In: Kelsen, et al, eds. Principles and Practice of Gastrointestinal Oncology. 1. Philadelphia, Pa: JB Lippincott Co; 2000.

  46. Lotze MT, Flickinger JC, Carr BI. Hepatobiliary Neoplasms. In: Devita VT, Hellman S, Rosenberg SA, eds. Principles and Practice of Oncology. 4th ed. Philadelphia, Pa: JB Lippincott Co; 1993:883-907.

  47. Malik IA, Aziz Z, Zaidi SH, Sethuraman G. Gemcitabine and Cisplatin is a highly effective combination chemotherapy in patients with advanced cancer of the gallbladder. Am J Clin Oncol. Apr 2003;26(2):174-7. [Medline].

  48. Malka D, Boige V, Dromain C, Debaere T, Pocard M, Ducreux M. Biliary tract neoplasms: update 2003. Curr Opin Oncol. Jul 2004;16(4):364-71. [Medline].

  49. Scheingraber S, Justinger C, Stremovskaia T, et al. The standardized surgical approach improves outcome of gallbladder cancer. World J Surg Oncol. 2007;5:55. [Medline].

  50. Stuver S, Trichopoulos D. Cancer of the Liver and Biliary Tract. In: Adami H, Hunter D, Trichopoulos D, eds. Textbook of Cancer Epidemiology. 2nd ed. New York, NY: Oxford University Press; 2008:308-332/12.

  51. Taner CB, Nagorney DM, Donohue JH. Surgical treatment of gallbladder cancer. J Gastrointest Surg. Jan 2004;8(1):83-9; discussion 89. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.