Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study

Tabernero, Josep; Yoshino, Takayuki; Cohn, Allen Lee; Obermannová, Radka; Bodoky, G.; Garcia-Carbonero, Rocío; Ciuleanu, Tudor-Eliade; Portnoy, David C.; Cutsem, Éric Van; Grothey, Axel; Prausová, Jana; García‐Alfonso, Pilar; Yamazaki, Kentaro; Clingan, Philip R.; Lonardi, Sara; Kim, Tae Won; Simms, Lorinda; Chang, Shao Chun; Nasroulah, Federico

doi:10.1016/s1470-2045(15)70127-0

Cited by 804 publications

(636 citation statements)

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“…Therefore, the (44). Phase III trials of the VEGFR inhibitor ramucirumab reported prolonged OS in non-small cell lung, gastric and colorectal cancer, (45)(46)(47)(48). Considering the results of the clinical trials using P-gp inhibitor or antiangiogenic agents (41,(43)(44)(45)(46)(47), the clinical efficacy of itracoanzole treatment in various types of cancer (Table II) implicated the additional anticancer activities, which was demonstrated in preclinical studies (Table I).…”

Section: Clinical Datamentioning

confidence: 99%

Repurposing itraconazole as an anticancer agent

et al. 2017

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Abstract. Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/β-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions. Clinical trials have suggested the clinical benefits of itraconazole monotherapy for prostate cancer and basal cell carcinoma, as well as the survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer. As drug repurposing is cost-effective and timesaving, a review was conducted of preclinical and clinical data focusing on the anticancer activity of itraconazole, and discusses the future directions for repurposing itraconazole as an anticancer agent.

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Section: Clinical Datamentioning

confidence: 99%

Repurposing itraconazole as an anticancer agent

et al. 2017

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“…More recently, ramucirumab combined to FOLFIRI as second-line treatment in metastatic CRC patients demonstrated to prolong survival versus FOLFIRI alone. In the RAISE study, a multicentre phase III double blind placebo controlled trial [32], in an intention to treat analysis the median survival time was 13.3 vs 11.7 months in the ramucirumab and placebo group, respectively. Grade 3-4 ramucirumab toxicities were neutropenia (38% of the patients), hypertension (11%), diarrhoea (11%), and fatigue (12%).…”

Section: Existing Therapiesmentioning

confidence: 99%

Novel anti-angiogenic therapeutic strategies in colorectal cancer

Tampellini

Sonetto

Scagliotti

2016

Expert Opinion on Investigational Drugs

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“…Ramucirumab is approved by the U.S. Food and Drug Administration for metastatic gastric cancer (REGARD and RAINBOW trials), non-small cell lung cancer (REVEL trial), and metastatic colorectal cancer (RAISE trial) [4][5][6][7]. Some VEGF inhibitors can prolong the QTc interval.…”

Section: Study Completed Pharmacokinetics / Pharmacodynamicsmentioning

confidence: 99%

Electrocardiographic Characterization of Ramucirumab on the Corrected QT Interval in a Phase II Study of Patients With Advanced Solid Tumors

et al. 2016

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LESSONS LEARNEDx Cardiotoxicity can be a serious complication of anticancer therapies. To enable earlier identification of drug-related cardiac effects, the International Conference on Harmonization (ICH) adopted the ICH E14 Guidelines for evaluating the potential for QT/ corrected QT (QTc) interval prolongation and proarrhythmic potential for nonantiarrhythmic drugs. x The results of the evaluation of ramucirumab on the QT/QTc interval show a lack of effect on QTc prolongation in patients with advanced cancer. ABSTRACTBackground. Ramucirumab is a human immunoglobulin G1 monoclonal antibody that specifically blocks vascular endothelial growth factor receptor-2 and is approved for the treatment of advanced gastric, non-small cell lung, and colorectal cancers. This phase II study was conducted to determine if treatment with ramucirumab causes prolongation of the corrected QT interval using Fridericia's formula (QTcF) in patients with advanced cancer. Methods. Patients received intravenous ramucirumab (10 mg/kg) every 21 days for 3 cycles.The first 16 patients received moxifloxacin (400 mg orally), an antibiotic associated with mild QT prolongation as a positive control. During cycle 3, determination of QTcF prolongation was made with triplicate electrocardiograms at multiple time points to compare with baseline.Results. Sixty-six patients received therapy; 51 patients completed 9 or more weeks of therapy for the complete QTcF evaluation period. The upper limit of the 90% twosided confidence intervals for the least square means of change in QTcF from baseline at each time point was less than 10 milliseconds. Concentration-QTcF analysis showed a visible, but not significant, negative association between

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Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study

Cited by 804 publications

References 21 publications

Repurposing itraconazole as an anticancer agent

Repurposing itraconazole as an anticancer agent

Novel anti-angiogenic therapeutic strategies in colorectal cancer

Electrocardiographic Characterization of Ramucirumab on the Corrected QT Interval in a Phase II Study of Patients With Advanced Solid Tumors

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