Bortezomib, Paclitaxel, and Carboplatin as a First-Line Regimen for Patients with Metastatic Esophageal, Gastric, and Gastroesophageal Cancer: Phase II Results from the North Central Cancer Treatment Group (N044B)

Jatoi, Aminah; Dakhil, Shaker R.; Foster, Nathan R.; Ma, Cynthia; Rowland, Kendrith M.; Moore, Dennis F.; Jaslowski, Anthony J.; Thomas, Sachdev; Hauge, Mark D.; Flynn, Patrick J.; Stella, Philip J.; Alberts, Steven R.

doi:10.1097/jto.0b013e31816de276

Cited by 31 publications

(13 citation statements)

References 15 publications

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“…The tumor response rate was lower than anticipated (23%). The MST for the cohort was 8.9 months [109] (Table 6). Further evaluations of bortezomib in combination with fluorouracil and leucovorin are ongoing in patients with metastatic or unresectable gastric cancer.…”

Section: Bortezomibmentioning

confidence: 99%

Molecular targeted agents for gastric and gastroesophageal junction cancer

Oshima

Masuda

2011

Surg Today

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Despite recent improvements in surgical techniques and chemotherapy, advanced cancers of the stomach and gastroesophageal junction (GEJ) continue to have poor clinical outcomes. However, molecules intimately related to cancer cell proliferation, invasion, and metastasis have been studied as candidates for molecular targeted agents. Target molecules, such as the epidermal growth factor receptor, vascular endothelial growth factor receptor, and P13k/Akt/mTor pathway, as well as the insulin-like growth factor receptor, c-Met pathways, fibroblast growth factor receptor, and other pathways are considered to be promising candidates for molecular targeted therapy for gastric and GEJ cancer. In this review we focus on the recent developments in targeting relevant pathways in these types of cancer.

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Section: Bortezomibmentioning

confidence: 99%

Molecular targeted agents for gastric and gastroesophageal junction cancer

Oshima

Masuda

2011

Surg Today

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“…The combination of irinotecan and bortezomib was examined in a multicenter study in advanced gastric cancer, with final results anticipated [38]. However, in a phase II study of metastatic gastroesophageal malignancies, bortezomib in combination with paclitaxel and carboplatin was considered inactive [39]. These data suggest again that inhibition of multiple oncogenic pathways may be critical to increasing anti-tumor activity with proteasome inhibition in gastric adenocarcinoma.…”

Section: Discussionmentioning

confidence: 98%

A multicenter, phase II study of Bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma

et al. 2010

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“…The need for biomarkers to assess drug sensitivity is demonstrated by recent clinical trial designed to determine the response rates of first line bortezomib in combination with paclitaxel and carboplatin in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia (19). The study was discontinued because the tumor response rate was lower than predictive value in the absence of clinical biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor activity of the proteasome inhibitor bortezomib in gastric cancer

Nakata

Hayakawa²,

Nakagawa³

et al. 2011

Int J Oncol

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Abstract. The prognosis of unresectable advanced gastric cancer has improved over the last decade due to advances in chemotherapy. However, molecular targeting in gastric cancer therapy has been poorly established and the 5-year survival rate is still <10%. The proteasome plays a pivotal role in the regulation of cell proliferation, apoptosis and differentiation in a variety of tumor cells. Bortezomib, a selective inhibitor of the proteasome, has prominent effects against several tumor types, including multiple myeloma. We examined the anti-tumor effects of bortezomib on gastric cancer cells in vitro and in subcutaneously transplanted nude mice. We demonstrated that among seven types of gastric cancer cells examined, treatment with bortezomib induced both apoptotic and anti-proliferative effects, resulting in a reduction in cell survival rates. The induction of apoptosis was observed to be dependent on the inhibition of nuclear factor κB (NF-κB) activation and the subsequent production of reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) activation. Interestingly, we observed that those cells with high levels of NF-κB activity were resistant to bortezomib treatment. Additionally, we demonstrated that the activation of the extracellular signal-regulated kinase (ERK1/2) was inhibited following bortezomib treatment, which may contribute to its anti-proliferative effects. We also observed anti-tumor effects of bortezomib in vivo. Bortezomib is a potential novel molecular targeting drug for the treatment of unresectable advanced gastric cancer.

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Bortezomib, Paclitaxel, and Carboplatin as a First-Line Regimen for Patients with Metastatic Esophageal, Gastric, and Gastroesophageal Cancer: Phase II Results from the North Central Cancer Treatment Group (N044B)

Abstract: As prescribed in this trial and for this indication, this regimen does not merit further testing.

Cited by 31 publications

References 15 publications

Molecular targeted agents for gastric and gastroesophageal junction cancer

Molecular targeted agents for gastric and gastroesophageal junction cancer

A multicenter, phase II study of Bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma

Anti-tumor activity of the proteasome inhibitor bortezomib in gastric cancer

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