ELC : Investigator Insights: VEGF and VEGFR Inhibitors in Gynecologic Malignancies

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CME expires 2013

Investigator Insights: VEGF and VEGFR Inhibitors in Gynecologic Malignancies

Preclinical and clinical investigations provide a strong rationale for the use of angiogenesis inhibitors in ovarian primary peritoneal/fallopian tube cancer, and a large variety of angiogenesis inhibitors are in late stages of development. Drs. Thomas Herzog and Robert Burger discuss VEGF and VEGFR inhibitors including emerging data from clinical trails, management of toxicities and the future direction of this field.

links to article/commentary/blogger's notes: Intravenous Aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study : The Lancet Oncology

Blogger's Note:  reposted from Jan 20th due to Lancet Editorial and reference - paper is open accdess

• pay specific attention to patient safety/adverse events; 

  • related article on the (beneficial) use of Aflibercept in colorectal cancer patients (Aflibercept Improves Survival In Metastatic Colon Cancer - December 2011)

Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double-blind, placebo-controlled study Aflibercept

 Interpretation

This study shows the effectiveness of VEGF blockade in the reduction of malignant ascites, but confirms the significant clinical risk of fatal bowel perforation in this population of patients with very advanced cancer. VEGF blockade should be used with caution in advanced ovarian cancer with abdominal carcinomatosis, and the benefit—risk balance should be thoroughly discussed for each patient.

 Commentary: 

VEGF Trap for the treatment of malignant ascites

Gerhild Becker, Hubert E Blum

"In view of the important pathogenetic role of VEGF in ascites formation, the efficacy of VEGF inhibitors have also been assessed in patients with symptomatic malignant ascites. Confirming the results of a recent open-label single-arm phase 2 trial,6 the randomised double-blind placebo-controlled study by Walter Gotlieb and colleagues7 in The Lancet Oncology shows the efficacy of aflibercept in patients with malignant ascites associated with advanced ovarian cancer and can be interpreted as proof of concept. The intervention and the control groups were homogenous, confounding variables controlled, and bias reduced. Therefore, the study has a high internal validity and shows the efficacy of aflibercept. With respect to the clinical implications of the results, symptom relief has to be weighed against discomfort and potentially life-threatening adverse events (three patients had fatal gastrointestinal complications in the aflibercept group vs one in the placebo group), since the treatment is applied to patients in a highly palliative situation. Careful patient selection could reduce the incidence of gastrointestinal perforations. However, before a general recommendation of aflibercept for the treatment of malignant ascites can be made, further studies, including comparative effectiveness research,8 (Blogger's Note: AND patient safety) are needed to compare the effectiveness of the different therapeutic strategies in daily clinical practice."

video: CFS Nov 2011: Active angiogenesis drugs in development - Prof Bradley Monk – University of California Irvine, USA

Contemporary Approaches in Targeting Angiogenesis | prIME Oncology

Topics

• Module One: Concepts in Angiogenesis Inhibition
• Module Two: Biomarkers in Angiogenesis
• Module Three: Optimizing Outcomes with Antiangiogenic Therapy in Non-Small Cell Lung Cancer
• Module Four: Optimizing Outcomes with Antiangiogenic Therapy in Colorectal Cancer
• Module Five: Optimizing Outcomes with Antiangiogenic Therapy in Glioblastoma
• Module Six: Practical Considerations in Patient Management Involving Antiangiogenic Therapy

Abstract/full access; TIMP-1 and VEGF-165 serum concentration during first-line therapy of ovarian cancer patients

Abstract (provisional)

Background

Angiogenesis appears to play an important role in ovarian cancer. Vascular endothelial growth factor (VEGF) has recently been implicated as a therapeutic target in ovarian cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1) is involved in tissue invasion and angiogenesis. The application of serum TIMP-1 and VEGF to monitor primary therapy and predict clinical outcome of patients with ovarian cancer is unclear.

Inherited Determinants of Ovarian Cancer Survival

"Conclusion: An extensive multiple-pathway assessment found evidence that inherited differences may play a role in outcome of ovarian cancer patients, particularly in genes within the angiogenesis and inflammation pathways. Our work supports efforts to target such mediators for therapeutic gain."