Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study

Zhu, Andrew X.; Meyerhardt, Jeffrey A.; Blaszkowsky, Lawrence S.; Kambadakone, Avinash; Muzikansky, Alona; Zheng, Hui; Clark, Jeffrey W.; Abrams, Thomas A.; Chan, Jennifer A.; Enzinger, Peter C.; Bhargava, Pankaj; Kwak, Eunice L.; Allen, Jill N.; Jain, Sanjay; Stuart, Keith; Horgan, Kerry; Sheehan, Susan; Fuchs, Charles S.; Ryan, David P.; Sahani, Dushyant V.

doi:10.1016/s1470-2045(09)70333-x

Cited by 270 publications

(151 citation statements)

References 30 publications

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“…Due to the overall poor prognosis of metastatic cholangiocarcinoma and limited treatment options, there is a clear need for identification of novel treatment options (26)(27)(28)(29). The role of anti-angiogenics and other targeted therapies have been evaluated in first and second line treatment of cholangiocarcinoma either in combination with gemcitabine based chemotherapy or 5 fluorouracil based therapy (26,27,(29)(30)(31). In a phase 2 study, GEMOX with bevacizumab (GEMOX-B) showed tolerable safety in patients with advanced BTCs (26).…”

Section: Discussionmentioning

confidence: 99%

“…The role of anti-angiogenics and other targeted therapies have been evaluated in first and second line treatment of cholangiocarcinoma either in combination with gemcitabine based chemotherapy or 5 fluorouracil based therapy (26,27,(29)(30)(31). In a phase 2 study, GEMOX with bevacizumab (GEMOX-B) showed tolerable safety in patients with advanced BTCs (26). GEMOX-B was given to 35 patients with advanced BTCs, 32 of which had not received any systemic therapy before.…”

Section: Discussionmentioning

confidence: 99%

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Advanced biliary tract cancer: clinical outcomes with ABC-02 regimen and analysis of prognostic factors in a tertiary care center in the United States

Agarwal

Sendilnathan

Siddiqi

et al. 2016

J. Gastrointest. Oncol.

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Background: Gemcitabine plus cisplatin (GC) is currently the standard regimen for advanced biliary tract cancers (BTC) based on the outcomes in ABC-02 trial. Multiple factors can affect outcomes in these patients. This retrospective review evaluates the University of Cincinnati experience with GC in advanced intrahepatic (IHC)/ extrahepatic cholangiocarcinoma (EHC) and gall bladder carcinoma (GBC). Methods: In this study approved by University of Cincinnati IRB, retrospective analysis of advanced BTC patients seen between 01/2008 and 01/2015 was done. Kaplan Meyer method was used to calculate progression free survival (PFS), and overall survival (OS). Cox model was used to test the association between baseline variables and OS/PFS, adjusting for gender and age at diagnosis. Patients were identified using ICD code for BT tumors, 26 patients met inclusion criteria: histologically proven advanced BTC that received GC as their initial chemotherapy. GC was given as per ABC-02 protocol with appropriate modifications until disease progression or unacceptable toxicities. Results: Median age at diagnosis was 62 years (range, 31-81 years). Eighteen (69%) were IHC, 5 EHC, 3 GBC, 61% male, 73% whites. Performance status (PS): 0-1: 69%, PS 2: 31%. Baseline CA19-9 data was available for 21 patients, (range 1 to 69,543), and abnormal CA19-9 was seen in 14 patients (54%). PFS was 4.5 months (95% CI: 3.1-8.9 months) and OS was 10.5 months (95 % CI: 7.9-18.8 months). OS at 6 and 12 months was 69% (18/26) and 42% (11/26). Thirty-eight percent (10/26) received 2nd line chemotherapy, of these 9/10 received 5FU based chemotherapy. Eleven percent (3/26) received 3rd line chemotherapy. Increase in baseline carcinoembryonic antigen (CEA), alanine aminotransferase, alkaline phosphatase (ALP) and total bilirubin was associated with increased risk of death while increase in baseline CEA and ALP was associated with increased risk of progression (P valve <0.05). In the group of patients who had all three major risk factors (PS ≥2, CEA >3, and stage IVb), the median survival was 2.9 months (95% CI: 2.6-9.3 months), which was significantly worse compared to rest of the population [median 18 months (95% CI: 5.4-19.5 months), P<0.01]. Conclusions: Our data supports the use of GC as a first line regimen for advance BTC in a non-clinical trial setting. Results are comparable to those reported in ABC-02 trial, despite inclusion of PS 2 patients whom constituted 31% of our population. In the patient population studied, baseline CEA and liver function test appeared able to predict response to GC in advanced BTC. Patients with all three high risk factors (PS ≥2, CEA >3, and stage IVb) did poorly and may need careful selection prior to initiating chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Advanced biliary tract cancer: clinical outcomes with ABC-02 regimen and analysis of prognostic factors in a tertiary care center in the United States

Agarwal

Sendilnathan

Siddiqi

et al. 2016

J. Gastrointest. Oncol.

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“…40 The VEGF expression has been detected in bile duct and gallbladder cancers and correlates with advanced disease stage and poor prognosis. Zhu et al, in a single-arm phase II study, have shown the safety and efficacy of bevacizumab 41 ; a recombinant humanized monoclonal antibody against VEGF, in combination with GEMOX, in patients with advanced BTC was established.…”

Section: Targeted Therapiesmentioning

confidence: 99%

The Value of Molecular Biomarkers in Biliary Tract Cancer in the Era of Targeted Therapy

Anand

Purl²,

Dhar

2011

Journal of Clinical and Experimental Hepatology

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“…Bevacizumab, a recombinant humanized monoclonal antibody directed against VEGF, is an important therapeutic agent with promising effect against several malignancies, including colorectal, lung, breast and renal cell cancers, and has been investigated in phase II studies in combination with other agents for biliary tract cancer [44,45]. The combination of Gemox plus bevacizumab yielded promising results, with a response rate of 40% and median overall survival of 12.7 months [44].…”

Section: Clinical Trials Of Anti-angiogenic Inhibitors For Biliary Trmentioning

confidence: 99%

“…The combination of Gemox plus bevacizumab yielded promising results, with a response rate of 40% and median overall survival of 12.7 months [44]. Inhibition of VEGF and EGFR by bevacizumab and erlotinib was tested in a phase II study, and modest efficacy was noted, with a response rate of 12% and median overall survival of 9.9 months [45].…”

Section: Clinical Trials Of Anti-angiogenic Inhibitors For Biliary Trmentioning

confidence: 99%

Targeted therapy for biliary-tract cancer

Furuse

2010

The Lancet Oncology

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Abstract:It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important.

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Efficacy and safety of gemcitabine, oxaliplatin, and bevacizumab in advanced biliary-tract cancers and correlation of changes in 18-fluorodeoxyglucose PET with clinical outcome: a phase 2 study

Cited by 270 publications

References 30 publications

Advanced biliary tract cancer: clinical outcomes with ABC-02 regimen and analysis of prognostic factors in a tertiary care center in the United States

Advanced biliary tract cancer: clinical outcomes with ABC-02 regimen and analysis of prognostic factors in a tertiary care center in the United States

The Value of Molecular Biomarkers in Biliary Tract Cancer in the Era of Targeted Therapy

Targeted therapy for biliary-tract cancer

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