BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer

Benson, Al B.; Kiss, Igor; Bridgewater, John; Eskens, Ferry A.L.M.; Sasse, Carolyn; Vossen, Sandra; Chen, Jihong; Sant, Charles Van; Ball, Howard; Keating, Anne; Krivoshik, Andrew

doi:10.1158/1078-0432.ccr-15-3117

Cited by 22 publications

(23 citation statements)

References 46 publications

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“…In the present study, the median PFS, median OS, median TTF and overall RR in the CapeOX plus bevacizumab group were 8.0 months, 22.5 months, 5.8 months and 42.1%, respectively. Several previous prospective studies reported that median PFS, median OS, and overall RR of the CapeOX plus bevacizumab regimen without intermittent oxaliplatin treatment were 9.6-10.0 months, 23.2-34.6 months, 6.7 days and 52.2-59.3%, respectively (Hurwitz et al 2012;Yalcin et al 2013;Uchima et al 2014;Benson et al 2016;Ogata et al 2016). The median PFS and median OS, median TTF and overall RR by CapeOX plus bevacizumab regimen with intermittent oxaliplatin treatment in the present study was slightly worse than those of the CapeOX plus bevacizumab regimen without intermittent oxaliplatin treatment in previous reports.…”

Section: Discussionmentioning

confidence: 99%

Intermittent Withdrawal of Oxaliplatin for Alleviating Neurotoxicity during Oxaliplatin-Based Chemotherapy for Japanese Patients with Inoperable or Metastatic Colorectal Cancer: A Phase 2 Multicenter Study

Kato

Imai

Gamoh

et al. 2018

Tohoku J. Exp. Med.

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Oxaliplatin-based chemotherapy is a well-established regimen for patients with inoperable and metastatic colorectal cancer. However, one of the major limitations of oxaliplatin-based chemotherapy is sensory neuropathy. It was previously reported that introduction of intermittent oxaliplatin treatment to an oxaliplatin-based regimen has a significant benefit on efficacy or safety. Here, we prospectively assessed whether efficacy and safety of first-line chemotherapy for advanced colorectal cancer are achieved by introduction of withdrawal of oxaliplatin treatment for a certain period (intermittent oxaliplatin treatment). The primary endpoint of the present study is to assess the progression free survival time on patients treated with chemotherapy (mFOLFOX6 (levofolinate, 5-fluorouracil and oxaliplatin combination therapy) plus bevacizumab or CapeOX (oxaliplatin and capecitabine combination therapy) plus bevacizumab) with intermittent oxaliplatin treatment. Bevacizumab is a humanized anti-vascular endothelial growth factor antibody. Median progression-free survival by the mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or the CapeOX plus bevacizumab with intermittent oxaliplatin treatment were 10.6 months (95% confidential interval [CI], 8.3-13.4 months) or 8.0 months (95% CI, 4.2-16.8 months), respectively. Overall response rate by the mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or CapeOX plus bevacizumab with intermittent oxaliplatin treatment was 55.1% or 42.1%, respectively. Grade 3 or 4 neuropathy was observed in 4.1% or 10.5% of patients treated with mFOLFOX6 plus bevacizumab with intermittent oxaliplatin treatment or CapeOX plus bevacizumab with intermittent oxaliplatin treatment, respectively. Introduction of intermittent oxaliplatin treatment has improved severe neuropathy in mFOLFOX6 plus bevacizumab regimen without reducing treatment efficacy.

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Section: Discussionmentioning

confidence: 99%

Intermittent Withdrawal of Oxaliplatin for Alleviating Neurotoxicity during Oxaliplatin-Based Chemotherapy for Japanese Patients with Inoperable or Metastatic Colorectal Cancer: A Phase 2 Multicenter Study

Kato

Imai

Gamoh

et al. 2018

Tohoku J. Exp. Med.

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“…Tivozanib activity has been also investigated in hepatocellular carcinoma in association with durvalumab [78] and in recurrent, platinum-resistant ovarian cancer, fallopian tube cancer, and primary peritoneal cancer [79,80]. Tivozanib has been studied in phase I and II clinical trials as monotherapy and in combination with other drugs for the treatment of STS [81], glioblastoma [82], breast [83], and colorectal cancers, and other advanced gastrointestinal cancers [84,85].…”

Section: Tivozanibmentioning

confidence: 99%

Diarylureas as Antitumor Agents

et al. 2021

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The diarylurea is a scaffold of great importance in medicinal chemistry as it is present in numerous heterocyclic compounds with antithrombotic, antimalarial, antibacterial, and anti-inflammatory properties. Some diarylureas, serine-threonine kinase or tyrosine kinase inhibitors, were recently reported in literature. The first to come into the market as an anticancer agent was sorafenib, followed by some others. In this review, we survey progress over the past 10 years in the development of new diarylureas as anticancer agents.

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“…47 Further clinical studies showed that NRP-1 was predictive for the RTKi tivozanib and bevacizumab in a Phase II trial of metastatic colorectal cancer. 48 Tumour microvessel density has also been explored as a potential predictive biomarker for bevacizumab response in a recent randomised control trial of ovarian cancer patients. 49 Patients who displayed higher pre-treatment tumour microvessel density gained a significant PFS benefit from the addition of bevacizumab to standard chemotherapy, in comparison with patients with low microvessel density.…”

Section: Vegf Biologymentioning

confidence: 99%

Targeting the vasculature of tumours: combining VEGF pathway inhibitors with radiotherapy

Kanthou

Tozer

2018

The British Journal of Radiology

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The development of blood vessels by the process of angiogenesis underpins the growth and metastasis of many tumour types. Various angiogenesis inhibitors targeted against vascular endothelial growth factor A (VEGF-A) and its receptors have entered the clinic more than a decade ago. However, despite substantial clinical improvements, their overall efficacy proved to be significantly lower than many of the pre-clinical studies had predicted. Antiangiogenic agents have been combined with chemotherapy, radiotherapy and more recently immunotherapy in many pre-clinical and clinical studies in an effort to improve their efficacy. To date, only their use alongside chemotherapy is approved as part of standard treatment protocols. Most pre-clinical studies have reported improved tumour control from the addition of antiangiogenic therapies to radiotherapy and progress has been made in unravelling the complex mechanisms through which VEGF inhibition potentiates radiotherapy responses. However, the efficacy of this combination is variable, and many questions still remain as to how best to administer the two modalities to achieve optimal response and minimal toxicity. One important limiting factor is that, unlike some other targeted therapies, antiangiogenic agents are not administered to selected patient populations, since biomarkers for identifying responders have not yet been established. Here, we outline VEGF biology and review current approaches that aim to identify biomarkers for stratifying patients for treatment with angiogenesis inhibitors. We also discuss current progress in elucidating mechanisms of interaction between radiotherapy and VEGF inhibitors. Ongoing clinical trials will determine whether these combinations will ultimately improve treatment outcomes for cancer patients.

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BATON-CRC: A Phase II Randomized Trial Comparing Tivozanib Plus mFOLFOX6 with Bevacizumab Plus mFOLFOX6 in Stage IV Metastatic Colorectal Cancer

Cited by 22 publications

References 46 publications

Intermittent Withdrawal of Oxaliplatin for Alleviating Neurotoxicity during Oxaliplatin-Based Chemotherapy for Japanese Patients with Inoperable or Metastatic Colorectal Cancer: A Phase 2 Multicenter Study

Intermittent Withdrawal of Oxaliplatin for Alleviating Neurotoxicity during Oxaliplatin-Based Chemotherapy for Japanese Patients with Inoperable or Metastatic Colorectal Cancer: A Phase 2 Multicenter Study

Diarylureas as Antitumor Agents

Targeting the vasculature of tumours: combining VEGF pathway inhibitors with radiotherapy

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