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."

abstract: Clinical predictors of (Avastin) bevacizumab-associated gastrointestinal perforation

Abstract

OBJECTIVES: Bevacizumab is a generally well-tolerated drug, but bevacizumab-associated gastrointestinal perforations (BAP) occur in 0 to 15% of patients with ovarian carcinoma. Our goal was to evaluate the clinical predictors of BAP in order to identify factors, which may preclude patients from receiving treatment.
METHODS: We conducted a review of patients with recurrent epithelial ovarian carcinoma treated with bevacizumab between 2006 and 2009. Demographic and treatment data were collected for statistical analysis.
RESULTS: Eighty-two patients were identified; perforation occurred in 8 (9.76%). Among patients with perforation, a significantly higher incidence of prior bowel surgeries (p=0.0008) and prior bowel obstruction or ileus.
CONCLUSIONS: Predicting BAP remains a challenge. Bowel obstruction or ileus appears to be associated with increased risk of BAP.

abstract: Imaging of the gastrointestinal complications of systemic chemotherapy

Abstract:

Gastrointestinal complications of chemotherapy may be serious and potentially life-threatening. Familiarity with and awareness of the potential complications associated with various chemotherapeutic agents/regimens is paramount to enable accurate and timely diagnosis. In this article we review the radiological manifestations of the most notable gastrointestinal complications associated with chemotherapeutic administration.

Article Outline (requires subscription/$$$)

Introduction

Neutropenic enterocolitis

Pseudomembranous colitis

Ulceration

Perforation

GI haemorrhage

Ileus

Obstruction

Mesenteric infarction

Conclusion

Figure 1. A 70-year-old woman on day 10 of idorubicin and cytosine arabinoside chemotherapy for acute myeloid leukaemia developed vomiting, abdominal pain, loose bloody stool, and was profoundly neutropenic. Intravenous contrast-enhanced CT demonstrates diffuse colonic mural thickening (black arrow), with surrounding mesenteric stranding (white curved arrow) and ascites (black curved arrow). The distribution is pan-colonic. This constellation of clinical and radiological findings is highly suggestive of neutropenic enterocolitis.

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(Avastin) Bevacizumab-induced small bowel perforation in a patient with breast cancer without intraabdominal metastases (abstract)

Postoperative Pulmonary Embolism Including Asymptomatic Case... : International Journal of Gynecological Cancer

Conclusions: A substantial number of postoperative PEs were occult, and identification of high-risk patients and routine SpO₂ level monitoring would reduce the diagnostic delay of PE after gynecologic surgery. Increasing age, longer operation time, and obesity were risks. The use of a perioperative intermittent pneumatic compression device in multimodal conditions might thus prevent PE. (pulmonary embolism/blood clot)

Mar 2010 abstract: Incidence and management of (Avastin) bevacizumab-associated gastrointestinal perforations in patients with recurrent ovarian carcinoma

METHODS: We identified all patients who received bevacizumab off protocol from August 2004-August 2008. We examined their medical records for reports of confirmed GI perforation, associated clinicopathological factors, treatment, and outcomes. RESULTS: Six (4%) of 160 patients with ovarian carcinoma who had been treated with bevacizumab developed GI perforation.