Bowel perforation in non-small cell lung cancer after bevacizumab therapy

Schellhaas, Elisabeth; Loddenkemper, Christoph; Schmittel, Alexander; Buhr, H. J.; Pohlen, U.

doi:10.1007/s10637-008-9162-z

Cited by 29 publications

(13 citation statements)

References 18 publications

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“…Otherwise, prednisolone or CPS, both of which were taken long-term by this patient, might cause bowel damage. Schellhaas et al (16) reported that diffuse thrombus formation led to perforation of the normal colon, but the present case exhibited diffuse mucosal damage without thrombus. Taken together, it would be more convincing to assume that bevacizumab and/or 5-FU are related to this extensive bowel necrosis.…”

Section: Discussioncontrasting

confidence: 58%

Extensive bowel necrosis related to bevacizumab in metastatic rectal cancer patient: a case report and review of literature

Takada

Hoshino

Ito

et al. 2014

Japanese Journal of Clinical Oncology

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Recently, bevacizumab has become a key drug for treatment of metastatic colorectal cancer. Molecularly targeted agents such as bevacizumab can cause life-threatening adverse effects, though they are generally considered less toxic than cytotoxic drugs. Here, we review the case of a 76-year-old male rectal cancer patient with liver metastasis who suffered extensive bowel necrosis after administration of 5-fluorouracil-based chemotherapy with bevacizumab, and required a subtotal colectomy and end-ileostomy. Microscopic findings revealed extensive mucosal necrosis in the resected colon specimen and necrosis at the muscularis propria of the descending colon. Pathological findings suggested that the mucosal damage induced by chemotherapy may be exacerbated by treatment with bevacizumab, resulting in extensive necrosis.

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Section: Discussioncontrasting

confidence: 58%

Extensive bowel necrosis related to bevacizumab in metastatic rectal cancer patient: a case report and review of literature

Takada

Hoshino

Ito

et al. 2014

Japanese Journal of Clinical Oncology

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“…29, 44 A limitation of the current study is our inability to examine GI wall involvement by tumor prospectively because no reliable methods of diagnosis or documentation have been established. Another possibility is that bevacizumab could limit the blood flow to the splanchnic microvasculature via thrombosis or vasoconstriction, 45,46 leading to GI ischemia, but evidence for this hypothesis is limited.…”

Section: Wwwjcoorgmentioning

confidence: 99%

Risk Factors for GI Adverse Events in a Phase III Randomized Trial of Bevacizumab in First-Line Therapy of Advanced Ovarian Cancer: A Gynecologic Oncology Group Study

Burger

Brady

Bookman

et al. 2014

JCO

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Purpose To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy. Patients and Methods Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage. Results Of 1,873 patients enrolled, 1,759 (94%) were evaluable, and 2.8% (50 of 1,759) experienced a GI AE: 10 of 587 (1.7%, R1), 20 of 587 (3.4%, R2), and 20 of 585 (3.4%, R3). Univariable analyses indicated that previous treatment of inflammatory bowel disease (IBD; P = .005) and small bowel resection (SBR; P = .032) or large bowel resection (LBR; P = .012) at primary surgery were significantly associated with a GI AE. The multivariable estimated relative odds of a GI AE were 13.4 (95% CI, 3.44 to 52.3; P < .001) for IBD; 2.05 (95% CI, 1.09 to 3.88; P = .026) for LBR; 1.95 (95% CI, 0.894 to 4.25; P = .093) for SBR; and 2.15 for bevacizumab exposure (aggregated 95% CI, 1.05 to 4.40; P = .036). Conclusion History of treatment for IBD, and bowel resection at primary surgery, increase the odds of GI AEs in patients receiving first-line platinum-taxane chemotherapy for advanced ovarian cancer. After accounting for these risk factors, concurrent bevacizumab doubles the odds of a GI AE, but is not appreciably increased by continuation beyond chemotherapy.

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“…Causes of bleeding include chemotherapy-induced ischaemia (particularly induced by taxanes13 37 and bevacizumab38), infections (particularly CMV and Candida), graft versus host disease (which can occur after stem cell transplantation when the newly transplanted material attacks the transplant recipient's body), autoimmune colitis after treatment with ipilimumab,11 acute radiotherapy-induced ulceration, drug-or radiotherapy-induced inflammatory bowel disease, neutropenic enterocolitis and oxaliplatin-induced portal hypertension 39. Patients should be managed like any other high-risk GI bleed.…”

Section: Gi Symptoms: the Acute Syndromesmentioning

confidence: 99%

Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer

Andreyev

Davidson

Gillespie

et al. 2011

Gut

241

194

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BackgoundThe number of patients with chronic gastrointestinal (GI) symptoms after cancer therapies which have a moderate or severe impact on quality of life is similar to the number diagnosed with inflammatory bowel disease annually. However, in contrast to patients with inflammatory bowel disease, most of these patients are not referred for gastroenterological assessment. Clinicians who do see these patients are often unaware of the benefits of targeted investigation (which differ from those required to exclude recurrent cancer), the range of available treatments and how the pathological processes underlying side effects of cancer treatment differ from those in benign GI disorders. This paper aims to help clinicians become aware of the problem and suggests ways in which the panoply of syndromes can be managed.MethodsA multidisciplinary literature review was performed to develop guidance to facilitate clinical management of GI side effects of cancer treatments.ResultsDifferent pathological processes within the GI tract may produce identical symptoms. Optimal management requires appropriate investigations and coordinated multidisciplinary working. Lactose intolerance, small bowel bacterial overgrowth and bile acid malabsorption frequently develop during or after chemotherapy. Toxin-negative Clostridium difficile and cytomegalovirus infection may be fulminant in immunosuppressed patients and require rapid diagnosis and treatment. Hepatic side effects include reactivation of viral hepatitis, sinusoidal obstruction syndrome, steatosis and steatohepatitis. Anticancer biological agents have multiple interactions with conventional drugs. Colonoscopy is contraindicated in neutropenic enterocolitis but endoscopy may be life-saving in other patients with GI bleeding. After cancer treatment, simple questions can identify patients who need referral for specialist management of GI symptoms. Other troublesome pelvic problems (eg, urinary, sexual, nutritional) are frequent and may also require specialist input. The largest group of patients affected by chronic GI symptoms are those who have been treated with pelvic radiotherapy. Their complex symptoms, often caused by more than one diagnosis, need systematic investigation by gastroenterologists when empirical treatments fail. All endoscopic and surgical interventions after radiotherapy are potentially hazardous as radiotherapy may induce significant local ischaemia. The best current evidence for effective treatment of radiation-induced GI bleeding is with sucralfate enemas and hyperbaric oxygen therapy.ConclusionsAll cancer units must develop simple methods to identify the many patients who need help and establish routine referral pathways to specialist gastroenterologists where patients can receive safe and effective treatment. Early contact with oncologists and/or specialist surgeons with input from the patient's family and friends often helps the gastroenterologist to refine management strategies. Increased training in the late effects of cancer treatment is required.

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Bowel perforation in non-small cell lung cancer after bevacizumab therapy

Cited by 29 publications

References 18 publications

Extensive bowel necrosis related to bevacizumab in metastatic rectal cancer patient: a case report and review of literature

Extensive bowel necrosis related to bevacizumab in metastatic rectal cancer patient: a case report and review of literature

Risk Factors for GI Adverse Events in a Phase III Randomized Trial of Bevacizumab in First-Line Therapy of Advanced Ovarian Cancer: A Gynecologic Oncology Group Study

Practice guidance on the management of acute and chronic gastrointestinal problems arising as a result of treatment for cancer

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