A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08

Wolmark, N.; Yothers, Greg; O'Connell, M. J.; Sharif, Saima; Atkins, James N.; Seay, Thomas E.; Feherenbacher, L.; O'Reilly, Seamus; Allegra, Carmen J.

doi:10.1200/jco.2009.27.18s.lba4

Cited by 55 publications

(37 citation statements)

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“…In a previous study, we reported that the chemotherapy drug, paclitaxel, which induces a rapid mobilization of CEPs, administered in combination with an antiangiogenic drug therapy had an enhanced treatment outcome and the progression of the established tumors decreased (11). In the current study, we show that similarly to paclitaxel, FOLFOX chemotherapy, a drug combination used to clinically treat colon cancer among other malignancies (45), induces CEP mobilization. Consequently, the concomitant administration of anti-VEGF-A and FOLFOX resulted in a significant inhibition of CEP mobilization, as previously documented for paclitaxel (11).…”

Section: Discussionsupporting

confidence: 61%

Differential Therapeutic Effects of Anti–VEGF-A Antibody in Different Tumor Models: Implications for Choosing Appropriate Tumor Models for Drug Testing

Alishekevitz

Bril

Loven

et al. 2014

Molecular Cancer Therapeutics

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We previously reported that the host response to certain chemotherapies can induce primary tumor regrowth, angiogenesis, and even metastases in mice, but the possible impact of anti-VEGF-A therapy in this context has not been fully explored. We, therefore, used combinations of anti-VEGF-A with chemotherapy on various tumor models in mice, including primary tumors, experimental lung metastases, and spontaneous lung metastases of 4T1-breast and CT26-colon murine cancer cell lines. Our results show that a combined treatment with anti-VEGF-A and folinic acid/5-fluorouracil/oxaliplatin (FOLFOX) but not with anti-VEGF-A and gemcitabine/cisplatinum (Gem/CDDP) enhances the treatment outcome partly due to reduced angiogenesis, in both primary tumors and experimental lung metastases models. However, neither treatment group exhibited an improved treatment outcome in the spontaneous lung metastases model, nor were changes in endothelial cell numbers found at metastatic sites. As chemotherapy has recently been shown to induce tumor cell invasion, we tested the invasion properties of tumor cells when exposed to plasma from FOLFOX-treated mice or patients with cancer. While plasma from FOLFOX-treated mice or patients induced invasion properties of tumor cells, the combination of anti-VEGF-A and FOLFOX abrogated these effects, despite the reduced plasma VEGF-A levels detected in FOLFOX-treated mice. These results suggest that the therapeutic impact of antiangiogenic drugs varies in different tumor models, and that anti-VEGF-A therapy can block the invasion properties of tumor cells in response to chemotherapy. These results may implicate an additional therapeutic role for anti-VEGF-A when combined with chemotherapy. Mol Cancer Ther; 13(1); 202-13. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 61%

Differential Therapeutic Effects of Anti–VEGF-A Antibody in Different Tumor Models: Implications for Choosing Appropriate Tumor Models for Drug Testing

Alishekevitz

Bril

Loven

et al. 2014

Molecular Cancer Therapeutics

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“…In addition, neither bevacizumab nor cetuximab improves overall survival or disease-free survival when given in combination with oxaliplatin-based chemotherapy in the adjuvant setting 57,58 . Overall, these results show how little is understood about the interaction of oxaliplatin with antibodies, and how useful pharmacodynamic studies would be in that regard.…”

Section: Oxaliplatin In Colorectal Cancermentioning

confidence: 99%

Oxaliplatin: A Review in the Era of Molecularly Targeted Therapy

2011

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molecularly targeted anticancer therapy with conventional cytotoxic chemotherapy. Such combinations can come about only through rational design of clinical trials, taking into account the pharmacology and clinical development of the drugs involved. It is therefore worthwhile revisiting classical chemotherapy agents, because this renewed knowledge could provide a foundation for future trials.Oxaliplatin is the newest platinum derivative in standard chemotherapy. Here, we review oxaliplatin from the pharmacologic and drug development perspectives, and we comment on possible associations of this drug with molecularly targeted therapy. CHEMICAL AND PHYSICAL PROPERTIES AND BIOTRANSFORMATIONOxaliplatin differs from cisplatin in that the amine groups of cisplatin are replaced by diaminocyclohexane (dach). The molecular weight of oxaliplatin is 397.3. It is slightly soluble in water, less so in methanol, and almost insoluble in ethanol and acetone 1 . Its full chemical name, oxalato(transl-1,2-diaminocyclohexane)platinum, refers to the presence of an oxalate "leaving group" and the dach carrier ligand, which are responsible, at least in part, for its unique properties 2,3 . For example, unlike cisplatin, oxaliplatin in plasma rapidly undergoes non-enzymatic transformation into reactive compounds because of displacement of the oxalate group, a process that complicates its pharmacokinetic profile. Most of the compounds appear to be pharmacologically inactive, but dichloro(dach) platinum complexes enter the cell, where they have cytotoxic properties. MECHANISMS OF ACTIONVarious mechanisms of action are ascribed to oxaliplatin. Like other platinum-based compounds, oxaliplatin exerts its cytotoxic effect mostly through dna damage. Apoptosis of cancer cells can be caused by formation of dna lesions, arrest of dna synthesis, ABSTRACT ObjectiveTo review preclinical and clinical data for oxaliplatin in the current context of molecularly targeted therapy.

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“…In this study BV increased the risk of wound healing complications (WHC), even if it was initiated 6 weeks from the time of surgery. Furthermore, it was suggested that extended use of BV can increase the long-term risk of WHC for up to 6 months after its cessation 18,34 .…”

Section: Bv-related Complications After Surgery Rct Data [Table 3]mentioning

confidence: 99%

Review: Incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer

Hompes

Ruers

2011

European Journal of Surgical Oncology (EJSO)

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To cite this version:Daphne Hompes, Theo Ruers. Review: Incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer. EJSO -European Journal of Surgical Oncology, WB Saunders, 2011, 37 (9) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. period of minimally 28 days should be respected before starting BV. Conclusion:Reported rates of BV-related SAE in relationship to surgery are low.

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A phase III trial comparing mFOLFOX6 to mFOLFOX6 plus bevacizumab in stage II or III carcinoma of the colon: Results of NSABP Protocol C-08

Cited by 55 publications

References 0 publications

Differential Therapeutic Effects of Anti–VEGF-A Antibody in Different Tumor Models: Implications for Choosing Appropriate Tumor Models for Drug Testing

Differential Therapeutic Effects of Anti–VEGF-A Antibody in Different Tumor Models: Implications for Choosing Appropriate Tumor Models for Drug Testing

Oxaliplatin: A Review in the Era of Molecularly Targeted Therapy

Review: Incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer

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