A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer

Iyer, Renuka; Pokuri, Venkata; Groman, Adrienne; Wei, Wen Bin; Malhotra, Usha; Iancu, Daniel; Grande, Catherine; Saab, Tanios B.

doi:10.1097/coc.0000000000000347

Cited by 64 publications

(40 citation statements)

References 32 publications

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“…Angiogenesis is critical for the metastasis of cancer cells, which is an independent factor determining the survival of CCA patients . However, the commonly used anti‐VEGF mAbs, such as bevacizumab, have not been demonstrated to improve the outcomes of patients with advanced CCA compared with historical controls when added to gemcitabine/capecitabine chemotherapeutic regimen . The benefits of VEGF inhibition therapies are transient and invariable.…”

Section: Discussionmentioning

confidence: 99%

“…1 However, the commonly used anti-VEGF mAbs, such as bevacizumab, have not been demonstrated to improve the outcomes of patients with advanced CCA compared with historical controls when added to gemcitabine/capecitabine chemotherapeutic regimen. 29 The benefits of VEGF inhibition therapies are transient and invariable. What is worse, anti-VEGF mAbs can also induce hypertension and renal toxicity because of its off-target effects.…”

Section: Vegf Inhibition-mediated Antiangiogenic Therapy Continuesmentioning

confidence: 99%

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Neuropilin‐1 regulated by miR‐320 contributes to the growth and metastasis of cholangiocarcinoma cells

Zhu

Jiang

Zhou

et al. 2017

Liver International

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Section: Discussionmentioning

confidence: 99%

Section: Vegf Inhibition-mediated Antiangiogenic Therapy Continuesmentioning

confidence: 99%

Neuropilin‐1 regulated by miR‐320 contributes to the growth and metastasis of cholangiocarcinoma cells

Zhu

Jiang

Zhou

et al. 2017

Liver International

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“…VEGF is overexpressed in BTCs and associated with enhanced metastasis, increased tumor recurrence, and worsened prognosis (34). Studies with antagonists of the VEGF pathway, including bevacizumab, cediranib, sorafenib have not yielded encouraging results (52)(53)(54)(55)(56).…”

Section: Vegfmentioning

confidence: 99%

Current biologics for treatment of biliary tract cancers

Zhao

Lim

2017

J. Gastrointest. Oncol.

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Biliary tract cancers (BTC) is a group of malignancies that arise from the epithelial cells of the biliary tree. These cancers are typically classified by anatomic site of origin: intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC). To date, complete surgical resection remains the mainstay of treatment especially for earlier stage disease. Unfortunately, most patients present with advanced or metastatic disease, when systemic chemotherapy is the only treatment option. Due to the paucity of effective treatments, BTCs have a dismal prognosis. There is a tremendous need to better understand the disease biology, discover new therapies, and improve clinical outcomes for this challenging disease. Next-generation sequencing has produced a more accurate and detailed picture of the molecular signatures in BTCs. The three BTC histologic subtypes are, in fact, quite molecularly distinct.IHCC commonly contain FGFR2 fusions and IDH 1 and 2 mutations, whereas EHCC and GBC tend to carry mutations in EGFR, HER2, and MAPK pathway. In light of this emerging knowledge, clinical trials have become more biomarker-driven, which allows capturing of subsets of patients that are most likely to respond to certain therapies. Many new and promising targeted therapeutics are currently in the pipeline.Here we review the genetic landscape of BTCs while focusing on new molecular targets and targeted therapeutics currently being investigated in biomarker-driven clinical trials.

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“…There are some studies combining chemotherapy (gem-cis) with immunotherapies or molecular therapies to determine if this combination offers enhanced tumor responses. Results of a multi-institutional phase II trial including the Roswell Park Cancer Institute investigated the addition of bevacizumab (BV) to gem-cap in ABC (23). Survival results for patients treated with gem-cap and BV (median PFS =8.1 mo and median OS =11.3 mo) were similar to those treated with gemcap only.…”

Section: Discussionmentioning

confidence: 83%

Gemcitabine and capecitabine for advanced biliary cancer

Gabriel

Gandhi

Attwood

et al. 2017

J. Gastrointest. Oncol.

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Background: Gemcitabine with capecitabine (gem-cap) is an established regimen for advanced biliary cancer (ABC) supported by our previously reported phase II trial. Here, we provide our updated experience. (69/129) experienced a grade 3/4 toxicity. The most common (35.7%) was a hematologic toxicity (neutropenia or thrombocytopenia) followed by infection (25.6%). Conclusions: Gem-cap provides similar survival outcomes to gemcitabine/cisplatin based on historical comparison to the ABC-2 trial (median PFS =8.0 mo and OS =11.7 mo). Gem-cap may offer the advantage of fewer adverse events compared to the levels reported in ABC-2 (grade 3/4 events 70.7%).

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A Multicenter Phase II Study of Gemcitabine, Capecitabine, and Bevacizumab for Locally Advanced or Metastatic Biliary Tract Cancer

Abstract: Addition of bevacizumab to gemcitabine/capecitabine did not improve outcome in an unselected group of patients with advanced BTC compared with historical controls. The selective benefit of vascular endothelial growth factor inhibition in BTC remains to be explored.

Cited by 64 publications

References 32 publications

Neuropilin‐1 regulated by miR‐320 contributes to the growth and metastasis of cholangiocarcinoma cells

Neuropilin‐1 regulated by miR‐320 contributes to the growth and metastasis of cholangiocarcinoma cells

Current biologics for treatment of biliary tract cancers

Gemcitabine and capecitabine for advanced biliary cancer

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