Gallbladder cancer medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
[[Gallbladder cancer]] (GBC) is a rare but highly fatal [[malignancy]]. The therapy for gallbladder cancer depends largely on the disease progression and the stage of cancer at the time of [[diagnosis]]. | [[Gallbladder cancer]] (GBC) is a rare but highly fatal [[malignancy]]. The therapy for [[gallbladder cancer]] depends largely on the disease progression and the stage of cancer at the time of [[diagnosis]]. | ||
==Medical Therapy == | ==Medical Therapy == | ||
| Line 10: | Line 10: | ||
*The only important [[Cure|curative]] modality for patients with GBC is surgery. | *The only important [[Cure|curative]] modality for patients with GBC is surgery. | ||
'''Medical Therapy for obstructive jaundice''' | '''Medical Therapy for obstructive jaundice''' | ||
* In most of patients with GBC biliary obstruction is the main cause for jaundice. | * In most of patients with GBC [[biliary]] obstruction is the main cause for [[jaundice]]. | ||
* Direct [[Infiltration (medical)|infiltration]] of the [[common hepatic duct]] by tumor is the actual cause.<ref name="pmid9038546">{{cite journal |vauthors=Kapoor VK, Pradeep R, Haribhakti SP, Singh V, Sikora SS, Saxena R, Kaushik SP |title=Intrahepatic segment III cholangiojejunostomy in advanced carcinoma of the gallbladder |journal=Br J Surg |volume=83 |issue=12 |pages=1709–11 |year=1996 |pmid=9038546 |doi= |url=}}</ref><ref name="pmid12354980">{{cite journal |vauthors=Piñol V, Castells A, Bordas JM, Real MI, Llach J, Montañà X, Feu F, Navarro S |title=Percutaneous self-expanding metal stents versus endoscopic polyethylene endoprostheses for treating malignant biliary obstruction: randomized clinical trial |journal=Radiology |volume=225 |issue=1 |pages=27–34 |year=2002 |pmid=12354980 |doi=10.1148/radiol.2243011517 |url=}}</ref> | * Direct [[Infiltration (medical)|infiltration]] of the [[common hepatic duct]] by tumor is the actual cause.<ref name="pmid9038546">{{cite journal |vauthors=Kapoor VK, Pradeep R, Haribhakti SP, Singh V, Sikora SS, Saxena R, Kaushik SP |title=Intrahepatic segment III cholangiojejunostomy in advanced carcinoma of the gallbladder |journal=Br J Surg |volume=83 |issue=12 |pages=1709–11 |year=1996 |pmid=9038546 |doi= |url=}}</ref><ref name="pmid12354980">{{cite journal |vauthors=Piñol V, Castells A, Bordas JM, Real MI, Llach J, Montañà X, Feu F, Navarro S |title=Percutaneous self-expanding metal stents versus endoscopic polyethylene endoprostheses for treating malignant biliary obstruction: randomized clinical trial |journal=Radiology |volume=225 |issue=1 |pages=27–34 |year=2002 |pmid=12354980 |doi=10.1148/radiol.2243011517 |url=}}</ref> | ||
* Maximum patients who present with [[jaundice]] are normally no longer amenable to a healing resection. | * Maximum patients who present with [[jaundice]] are normally no longer amenable to a healing [[resection]]. | ||
* Biliary or [[intestinal]] [[bypass]] are considered one of the therapy for palliation of [[obstructive jaundice]]. | * [[Biliary]] or [[intestinal]] [[bypass]] are considered one of the therapy for [[palliation]] of [[obstructive jaundice]]. | ||
* To relive palliate [[jaundice]] and [[pruritus]] as little as 30 percent of the liver [[parenchyma]] drainage by using stents should be necessary. | * To relive palliate [[jaundice]] and [[pruritus]] as little as 30 percent of the liver [[parenchyma]] drainage by using stents should be necessary. | ||
* And stents are placed by using [[endoscope]]. | * And stents are placed by using [[endoscope]]. | ||
| Line 22: | Line 22: | ||
* The first site of failure is usually locoregional when using with or without [[chemotherapy]]. | * The first site of failure is usually locoregional when using with or without [[chemotherapy]]. | ||
* For locally advanced unresectable GBC chemoradiotherapy is an acceptable despite uncertainty about the benefits.<ref name="pmid27075323">{{cite journal |vauthors=Engineer R, Goel M, Chopra S, Patil P, Purandare N, Rangarajan V, Ph R, Bal M, Shrikhande S, Shrivastava SK, Mehta S |title=Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Gallbladder Cancers: A New Paradigm |journal=Ann. Surg. Oncol. |volume=23 |issue=9 |pages=3009–15 |year=2016 |pmid=27075323 |doi=10.1245/s10434-016-5197-0 |url=}}</ref> | * For locally advanced unresectable GBC chemoradiotherapy is an acceptable despite uncertainty about the benefits.<ref name="pmid27075323">{{cite journal |vauthors=Engineer R, Goel M, Chopra S, Patil P, Purandare N, Rangarajan V, Ph R, Bal M, Shrikhande S, Shrivastava SK, Mehta S |title=Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Gallbladder Cancers: A New Paradigm |journal=Ann. Surg. Oncol. |volume=23 |issue=9 |pages=3009–15 |year=2016 |pmid=27075323 |doi=10.1245/s10434-016-5197-0 |url=}}</ref> | ||
* For patients with locally advanced, unresectable GBC, National Comprehensive Cancer Network (NCCN) suggests chemotherapy based on fluoropyrimidine or [[Palliative therapy|palliative]] chemotherapy. | * For patients with locally advanced, unresectable GBC, National Comprehensive Cancer Network (NCCN) suggests chemotherapy based on fluoropyrimidine or [[Palliative therapy|palliative]] [[chemotherapy]]. | ||
'''Systemic Chemotherapy''' | '''Systemic Chemotherapy''' | ||
* In the treatment of advanced GBC systemic [[chemotherapy]] provides little benefit. | * In the treatment of advanced GBC systemic [[chemotherapy]] provides little benefit. | ||
| Line 33: | Line 33: | ||
* The median [[Survival rate|survival]] was usually less than six months when [[Fluorouracil|FU]] alone or FU-based combination therapies used.<ref name="pmid117058502">{{cite journal |vauthors=Patt YZ, Hassan MM, Lozano RD, Waugh KA, Hoque AM, Frome AI, Lahoti S, Ellis L, Vauthey JN, Curley SA, Schnirer II, Raijman I |title=Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer |journal=Clin. Cancer Res. |volume=7 |issue=11 |pages=3375–80 |year=2001 |pmid=11705850 |doi= |url=}}</ref> | * The median [[Survival rate|survival]] was usually less than six months when [[Fluorouracil|FU]] alone or FU-based combination therapies used.<ref name="pmid117058502">{{cite journal |vauthors=Patt YZ, Hassan MM, Lozano RD, Waugh KA, Hoque AM, Frome AI, Lahoti S, Ellis L, Vauthey JN, Curley SA, Schnirer II, Raijman I |title=Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer |journal=Clin. Cancer Res. |volume=7 |issue=11 |pages=3375–80 |year=2001 |pmid=11705850 |doi= |url=}}</ref> | ||
* Combination regimens or [[leucovorin]]-modulated FU report higher response rates and marginally longer survival. | * Combination regimens or [[leucovorin]]-modulated FU report higher response rates and marginally longer survival. | ||
* | * When used in combinations regimes like [[leucovorin]]-modulated FU have higher chances of marginally longer survival.<ref name="pmid8192106">{{cite journal |vauthors=Kajanti M, Pyrhönen S |title=Epirubicin-sequential methotrexate-5-fluorouracil-leucovorin treatment in advanced cancer of the extrahepatic biliary system. A phase II study |journal=Am. J. Clin. Oncol. |volume=17 |issue=3 |pages=223–6 |year=1994 |pmid=8192106 |doi= |url=}}</ref><ref name="pmid6092556">{{cite journal |vauthors=Harvey JH, Smith FP, Schein PS |title=5-Fluorouracil, mitomycin, and doxorubicin (FAM) in carcinoma of the biliary tract |journal=J. Clin. Oncol. |volume=2 |issue=11 |pages=1245–8 |year=1984 |pmid=6092556 |doi=10.1200/JCO.1984.2.11.1245 |url=}}</ref> | ||
'''Infusional FU plus cisplatin''' '''therapy''' | '''Infusional FU plus cisplatin''' '''therapy''' | ||
* Median survival for patients with [[Gallbladder cancer|GBC]] was 11.5 months when infusional FU has been combined | * Median survival for patients with [[Gallbladder cancer|GBC]] was 11.5 months when infusional FU has been combined with [[cisplatin]].<ref name="pmid9681080">{{cite journal |vauthors=Ducreux M, Rougier P, Fandi A, Clavero-Fabri MC, Villing AL, Fassone F, Fandi L, Zarba J, Armand JP |title=Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin |journal=Ann. Oncol. |volume=9 |issue=6 |pages=653–6 |year=1998 |pmid=9681080 |doi= |url=}}</ref> | ||
** Preferred regimen (1): [[fluorouracil]] 1 gm/ | ** Preferred regimen (1): [[fluorouracil]] 1 gm/m2 continuous infusion for 5 days. | ||
** Preferred regimen (2): [[cisplatin]] 100 mg/m2 on day 2. | ** Preferred regimen (2): [[cisplatin]] 100 mg/m2 on day 2. | ||
* Median survival for patients with GBC was 10 months when infusional FU has been combined with cisplatin and [[epirubicin]]. | * Median survival for patients with GBC was 10 months when infusional FU has been combined with cisplatin and [[epirubicin]]. | ||
** Preferred regimen (1): [[fluorouracil]] 200 mg/m2 per day by continuous [[intravenous]] infusion throughout the treatment. | ** Preferred regimen (1): [[fluorouracil]] 200 mg/m2 per day by continuous [[intravenous]] infusion throughout the treatment. | ||
** Preferred regimen (2): | ** Preferred regimen (2): [[Cisplatin]] 60 mg/m2 on day 1 [[epirubicin]] 50 mg/m2 repeated cycle every 21 days. | ||
'''Capecitabine with and without oxaliplatin''' | '''Capecitabine with and without oxaliplatin''' | ||
* The median survival was 11.3 months. | * The median survival was 11.3 months. | ||
** Preferred regimen (1): [[Capecitabine]] 1000 mg/m2 twice daily on days 1 to 14. | ** Preferred regimen (1): [[Capecitabine]] 1000 mg/m2 twice daily on days 1 to 14. | ||
** Preferred regimen (2): [[ | ** Preferred regimen (2): [[Oxaliplatin]] 130 mg/m2 over one hour on day 1. | ||
'''Docetaxel''' | '''Docetaxel''' | ||
* | * Preliminary results suggest minimal activity for when [[docetaxel]] used.<ref name="pmid11576836">{{cite journal |vauthors=Papakostas P, Kouroussis C, Androulakis N, Samelis G, Aravantinos G, Kalbakis K, Sarra E, Souglakos J, Kakolyris S, Georgoulias V |title=First-line chemotherapy with docetaxel for unresectable or metastatic carcinoma of the biliary tract. A multicentre phase II study |journal=Eur. J. Cancer |volume=37 |issue=15 |pages=1833–8 |year=2001 |pmid=11576836 |doi= |url=}}</ref> <ref name="pmid12201499">{{cite journal |vauthors=Kuhn R, Hribaschek A, Eichelmann K, Rudolph S, Fahlke J, Ridwelski K |title=Outpatient therapy with gemcitabine and docetaxel for gallbladder, biliary, and cholangio-carcinomas |journal=Invest New Drugs |volume=20 |issue=3 |pages=351–6 |year=2002 |pmid=12201499 |doi= |url=}}</ref> | ||
** Preferred regimen (1): [[Docetaxel]] 100 mg/m2 every 21 days. | ** Preferred regimen (1): [[Docetaxel]] 100 mg/m2 every 21 days. | ||
'''Molecularly targeted therapy''' | '''Molecularly targeted therapy''' | ||
'''Erlotinib''' | '''Erlotinib''' | ||
* Blockade of the epidermal growth factor receptor ([[EGFR]]) by erlotinib shows possible benefit.<ref name="pmid16601431">{{cite journal |vauthors=Park BK, Paik YH, Park JY, Park KH, Bang S, Park SW, Chung JB, Park YN, Song SY |title=The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma |journal=Am. J. Clin. Oncol. |volume=29 |issue=2 |pages=138–42 |year=2006 |pmid=16601431 |doi=10.1097/01.coc.0000204402.29830.08 |url=}}</ref> | * Blockade of the epidermal growth factor receptor ([[EGFR]]) by [[erlotinib]] shows possible benefit.<ref name="pmid16601431">{{cite journal |vauthors=Park BK, Paik YH, Park JY, Park KH, Bang S, Park SW, Chung JB, Park YN, Song SY |title=The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma |journal=Am. J. Clin. Oncol. |volume=29 |issue=2 |pages=138–42 |year=2006 |pmid=16601431 |doi=10.1097/01.coc.0000204402.29830.08 |url=}}</ref> | ||
** Preferred regimen (1): [[Erlotinib]] 150 mg daily. | ** Preferred regimen (1): [[Erlotinib]] 150 mg daily. | ||
'''Erlotinib plus bevacizumab''' | '''Erlotinib plus bevacizumab''' | ||
Latest revision as of 15:28, 10 January 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Manpreet Kaur, MD [2]
Overview
Gallbladder cancer (GBC) is a rare but highly fatal malignancy. The therapy for gallbladder cancer depends largely on the disease progression and the stage of cancer at the time of diagnosis.
Medical Therapy
There are different types of treatment for patients with gallbladder cancer.
- The only important curative modality for patients with GBC is surgery.
Medical Therapy for obstructive jaundice
- In most of patients with GBC biliary obstruction is the main cause for jaundice.
- Direct infiltration of the common hepatic duct by tumor is the actual cause.[1][2]
- Maximum patients who present with jaundice are normally no longer amenable to a healing resection.
- Biliary or intestinal bypass are considered one of the therapy for palliation of obstructive jaundice.
- To relive palliate jaundice and pruritus as little as 30 percent of the liver parenchyma drainage by using stents should be necessary.
- And stents are placed by using endoscope.
- Percutaneous self-expanding metal stent placing is an alternative to endoscopically placed stents.
Radiotherapy
- If patients are symptomatic consider external beam radiation therapy (EBRT) for palliative management.[3][4]
- A combination of chemotherapy and RT is considered in locally advanced unresectable disease.
- The first site of failure is usually locoregional when using with or without chemotherapy.
- For locally advanced unresectable GBC chemoradiotherapy is an acceptable despite uncertainty about the benefits.[5]
- For patients with locally advanced, unresectable GBC, National Comprehensive Cancer Network (NCCN) suggests chemotherapy based on fluoropyrimidine or palliative chemotherapy.
Systemic Chemotherapy
- In the treatment of advanced GBC systemic chemotherapy provides little benefit.
- A range of 10 to 60 % response rate is observed with chemotherapy.
- Drugs that used in chemotherapy are:[6]
Fluorouracil (FU) based therapy
- The median survival was usually less than six months when FU alone or FU-based combination therapies used.[7]
- Combination regimens or leucovorin-modulated FU report higher response rates and marginally longer survival.
- When used in combinations regimes like leucovorin-modulated FU have higher chances of marginally longer survival.[8][9]
Infusional FU plus cisplatin therapy
- Median survival for patients with GBC was 11.5 months when infusional FU has been combined with cisplatin.[10]
- Preferred regimen (1): fluorouracil 1 gm/m2 continuous infusion for 5 days.
- Preferred regimen (2): cisplatin 100 mg/m2 on day 2.
- Median survival for patients with GBC was 10 months when infusional FU has been combined with cisplatin and epirubicin.
- Preferred regimen (1): fluorouracil 200 mg/m2 per day by continuous intravenous infusion throughout the treatment.
- Preferred regimen (2): Cisplatin 60 mg/m2 on day 1 epirubicin 50 mg/m2 repeated cycle every 21 days.
Capecitabine with and without oxaliplatin
- The median survival was 11.3 months.
- Preferred regimen (1): Capecitabine 1000 mg/m2 twice daily on days 1 to 14.
- Preferred regimen (2): Oxaliplatin 130 mg/m2 over one hour on day 1.
Docetaxel
- Preliminary results suggest minimal activity for when docetaxel used.[11] [12]
- Preferred regimen (1): Docetaxel 100 mg/m2 every 21 days.
Molecularly targeted therapy
Erlotinib
- Blockade of the epidermal growth factor receptor (EGFR) by erlotinib shows possible benefit.[13]
- Preferred regimen (1): Erlotinib 150 mg daily.
Erlotinib plus bevacizumab
- Preferred regimen (1): Bevacizumab 5 mg/kg every two weeks plus erlotinib 150 mg once daily.[14]
References
- ↑ Kapoor VK, Pradeep R, Haribhakti SP, Singh V, Sikora SS, Saxena R, Kaushik SP (1996). "Intrahepatic segment III cholangiojejunostomy in advanced carcinoma of the gallbladder". Br J Surg. 83 (12): 1709–11. PMID 9038546.
- ↑ Piñol V, Castells A, Bordas JM, Real MI, Llach J, Montañà X, Feu F, Navarro S (2002). "Percutaneous self-expanding metal stents versus endoscopic polyethylene endoprostheses for treating malignant biliary obstruction: randomized clinical trial". Radiology. 225 (1): 27–34. doi:10.1148/radiol.2243011517. PMID 12354980.
- ↑ Ben-David MA, Griffith KA, Abu-Isa E, Lawrence TS, Knol J, Zalupski M, Ben-Josef E (2006). "External-beam radiotherapy for localized extrahepatic cholangiocarcinoma". Int. J. Radiat. Oncol. Biol. Phys. 66 (3): 772–9. doi:10.1016/j.ijrobp.2006.05.061. PMID 17011452.
- ↑ Jarnagin WR, Ruo L, Little SA, Klimstra D, D'Angelica M, DeMatteo RP, Wagman R, Blumgart LH, Fong Y (2003). "Patterns of initial disease recurrence after resection of gallbladder carcinoma and hilar cholangiocarcinoma: implications for adjuvant therapeutic strategies". Cancer. 98 (8): 1689–700. doi:10.1002/cncr.11699. PMID 14534886.
- ↑ Engineer R, Goel M, Chopra S, Patil P, Purandare N, Rangarajan V, Ph R, Bal M, Shrikhande S, Shrivastava SK, Mehta S (2016). "Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Gallbladder Cancers: A New Paradigm". Ann. Surg. Oncol. 23 (9): 3009–15. doi:10.1245/s10434-016-5197-0. PMID 27075323.
- ↑ Patt YZ, Hassan MM, Lozano RD, Waugh KA, Hoque AM, Frome AI, Lahoti S, Ellis L, Vauthey JN, Curley SA, Schnirer II, Raijman I (2001). "Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer". Clin. Cancer Res. 7 (11): 3375–80. PMID 11705850.
- ↑ Patt YZ, Hassan MM, Lozano RD, Waugh KA, Hoque AM, Frome AI, Lahoti S, Ellis L, Vauthey JN, Curley SA, Schnirer II, Raijman I (2001). "Phase II trial of cisplatin, interferon alpha-2b, doxorubicin, and 5-fluorouracil for biliary tract cancer". Clin. Cancer Res. 7 (11): 3375–80. PMID 11705850.
- ↑ Kajanti M, Pyrhönen S (1994). "Epirubicin-sequential methotrexate-5-fluorouracil-leucovorin treatment in advanced cancer of the extrahepatic biliary system. A phase II study". Am. J. Clin. Oncol. 17 (3): 223–6. PMID 8192106.
- ↑ Harvey JH, Smith FP, Schein PS (1984). "5-Fluorouracil, mitomycin, and doxorubicin (FAM) in carcinoma of the biliary tract". J. Clin. Oncol. 2 (11): 1245–8. doi:10.1200/JCO.1984.2.11.1245. PMID 6092556.
- ↑ Ducreux M, Rougier P, Fandi A, Clavero-Fabri MC, Villing AL, Fassone F, Fandi L, Zarba J, Armand JP (1998). "Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin". Ann. Oncol. 9 (6): 653–6. PMID 9681080.
- ↑ Papakostas P, Kouroussis C, Androulakis N, Samelis G, Aravantinos G, Kalbakis K, Sarra E, Souglakos J, Kakolyris S, Georgoulias V (2001). "First-line chemotherapy with docetaxel for unresectable or metastatic carcinoma of the biliary tract. A multicentre phase II study". Eur. J. Cancer. 37 (15): 1833–8. PMID 11576836.
- ↑ Kuhn R, Hribaschek A, Eichelmann K, Rudolph S, Fahlke J, Ridwelski K (2002). "Outpatient therapy with gemcitabine and docetaxel for gallbladder, biliary, and cholangio-carcinomas". Invest New Drugs. 20 (3): 351–6. PMID 12201499.
- ↑ Park BK, Paik YH, Park JY, Park KH, Bang S, Park SW, Chung JB, Park YN, Song SY (2006). "The clinicopathologic significance of the expression of vascular endothelial growth factor-C in intrahepatic cholangiocarcinoma". Am. J. Clin. Oncol. 29 (2): 138–42. doi:10.1097/01.coc.0000204402.29830.08. PMID 16601431.
- ↑ Lubner SJ, Mahoney MR, Kolesar JL, Loconte NK, Kim GP, Pitot HC, Philip PA, Picus J, Yong WP, Horvath L, Van Hazel G, Erlichman CE, Holen KD (2010). "Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study". J. Clin. Oncol. 28 (21): 3491–7. doi:10.1200/JCO.2010.28.4075. PMC 2917213. PMID 20530271.