Trial reportInvestigational new drugs2011
A multicenter, phase II study of bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.
Trial report in Investigational new drugs, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00074009 (A Multicenter, Open-Label, Two-Stage, Phase II Study Of PS-341), which is not on this map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Open-Label, Two-Stage, Phase II Study Of PS-341 (LDP-341, NSC # 681239) In Patients With Unresectable Or Metastatic Gastric Adenocarcinoma
Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach.Investigational new drugs · 2014Trial
- A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.Cancer chemotherapy and pharmacology · 2013Trial
- Proteasome inhibition enhances lysosome-mediated targeted protein degradation.Cell death & disease · 2026Article
- Wogonin derivative V8 enhances bortezomib efficacy in gastric carcinoma by disrupting lysosome-mediated drug resistance.World journal of gastroenterology · 2026Article
- UPS: Opportunities and challenges for gastric cancer treatment.Frontiers in oncology · 2023Review
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Review
- NF-κB signaling in inflammation and cancer.MedComm · 2021Review
- The promises and challenges of patient-derived tumor organoids in drug development and precision oncology.Animal models and experimental medicine · 2019Review
- Epithelial plasticity and cancer stem cells: Major mechanisms of cancer pathogenesis and therapy resistance.World journal of stem cells · 2017Review
- Molecular Pathways: The Balance between Cancer and the Immune System Challenges the Therapeutic Specificity of Targeting Nuclear Factor-κB Signaling for Cancer Treatment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Review
- New advances in targeted gastric cancer treatment.World journal of gastroenterology · 2016Review
- A first-in-human dose-escalation study of the oral proteasome inhibitor oprozomib in patients with advanced solid tumors.Investigational new drugs · 2016Article
- Article
- Molecular pathways: linking tumor microenvironment to epithelial-mesenchymal transition in metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Review
- The ubiquitin-proteasome system: opportunities for therapeutic intervention in solid tumors.Endocrine-related cancer · 2015Review
- Role of E3 ubiquitin ligases in gastric cancer.World journal of gastroenterology · 2015Review
- Benchmarking of gastric cancer sensitivity to anti-cancer drugs ex vivo as a basis for drug selection in systemic and intraperitoneal therapy.Journal of experimental & clinical cancer research : CR · 2014Article
- BAY 11-7082, a nuclear factor-κB inhibitor, induces apoptosis and S phase arrest in gastric cancer cells.Journal of gastroenterology · 2014Article
- A phase I trial of bortezomib in combination with epirubicin, carboplatin and capecitabine (ECarboX) in advanced oesophagogastric adenocarcinoma.Investigational new drugs · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
purposeThe transcription factor nuclear factor-kB (NFkB) is implicated in gastric cancer carcinogenesis and survival, and its inhibition by proteosome inhibition is associated with preclinical gastric cancer anti-tumor activity. We examined the single agent efficacy of bortezomib, a selective proteasome inhibitor, in gastric adenocarcinoma. EXPERIMENTAL
designWe performed a phase II trial of bortezomib in patients with advanced gastric adenocarcinoma. Bortezomib 1.3 mg/m(2) was administered on days 1, 4, 8, and 11 every 21 days. The primary endpoint was objective response rate(RR); the null hypothesis was RR <1% versus the alternative ≥15%. One response in the first stage(15 patients) was required before proceeding with an additional 18 patients. If at least 2 or more responses out of 33 were observed, further study with bortezomib was warranted. Correlative studies evaluated pre-treatment tumor expression of NFkB, IkB, p53, p21, and cyclin D1.
resultsWe enrolled 16 patients (15 evaluable for response) from four institutions. No patients demonstrated an objective response(95% CI, 0-22%); one patient achieved stable disease. Fourteen out of 16 patients experienced ≥ grade 2 toxicity. The most common toxicity was fatigue in six patients (n = 4 grade 2, n = 2 grade 3). Seven patients experienced neuropathy (n = 5 grade 1, and 1 each grade 2 and 3). Seven (60%) had high cytoplasmic staining for NFkB.
conclusionsSingle agent bortezomib is inactive in metastatic gastric adenocarcinoma and should not be pursued. Future study of proteasome inhibition in gastric adenocarcinoma should be considered in combination with targeted inhibition of other non-overlapping oncogenic pathways as a potential rational approach.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.