Cancer Treatment Today » Gastroenterology

Antibodies to inflixumab

M Levin, MD — Thu, 26 Dec 2013 16:17:57 +0000

Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). Lower drug levels can mean less effect ont eh disease. It is clinically useful to be able to assess and predict diminishing response. A recent meta-analysis concluded that the presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. However, most studies were flawed in that published studies on this topic lack uniform reporting of outcomes and high risk of bias was present in all the included studies.

Similar conclusions are reached by reviews that look at this question and are likewise limited in the same way. For example, a recent paper outlines why antibodies to infliximab (ATI) cannot be used as a surrogate marker for immunogenicity,
or to predict clinical outcome or safety. This is because up to half of patients still need dose adjustment for recurrent symptoms and 20% of patients lose response, even when treatment is optimised to avoid ATI through scheduled maintenance therapy or concomitant immunomodulators. The effects of ATI is, therefore, diluted statistically in these studies.

Thus far many questions persist about how useful ATI testing can be. Measurement of serum antibodies to infliximab has not received clearance by the FDA andthere is not sufficient peer-reviewed scientific literature that demonstrates that the procedure is effective.

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Octreotide in gastrointentinal angiodysplasia – pro

M Levin, MD — Tue, 18 Dec 2012 22:40:34 +0000

Angiodysplasias are usually asymptomatic but they can cause of GI bleeding in 3–6% of all patients and are a more common cause of beeeding in the elderly. It is notoriously difficult to treat. A number of reports suggest that it is a valuable adjunct in the treatment of gastro-inestinal dysplasia and can decrease bleeding. There are no supportive guidelines to my knowledge but the role of somatostatin analogues for refractory bleeding GI angiodysplasias has been systematically reviewed by Brown et al.
He concluded: “A significant number of patients with bleeding gastrointestinal angiodysplasia respond to treatment with octreotide by reducing the need for blood products. As all the included studies had small sample sizes, multicenter randomized trials are needed to confirm these findings. However, it seems reasonable to administer octreotide especially in patients with refractory bleeding, inaccessible lesions and in patients at high risk for other interventions.”.

Rivera M, Lucero J, Guerrero A, Márquez JL, Montes R, Suñer M, Ruiz A, Valdivia MA, Mateos J. Octreotide in the treatment of angiodysplasia in patients with advanced chronic renal failure.Nefrologia. 2005;25(3):332-5.

Junquera F, Saperas E, Videla S, et al. Long-term efficacy of octreotide in the prevention of recurrent bleeding from gastrointestinal angiodysplasia. Am J Gastroenterol 2007; 102:254.

Brown C, Subramanian V, Wilcox CM, Peter S. Somatostatin analogues in the treatment of recurrent bleeding from gastrointestinal vascular malformations: an overview and systematic review of prospective observational studies. Dig Dis Sci 2010; 55:2129.

Scaglione G, Pietrini L, Russo F, et al. Long-acting octreotide as rescue therapy in chronic bleeding from gastrointestinal angiodysplasia. Aliment Pharmacol Ther 2007; 26:935.

Molina-Infante J, Perez-Gallardo B. Somatostatin analogues for bleeding gastrointestinal angiodysplasias: when should thalidomide be prescribed?. Dig Dis Sci. Jan 2011;56(1):266-7.

Bon C, Aparicio T, Vincent M, et al. Long-acting somatostatin analogues decrease blood transfusion requirements in patients with refractory gastrointestinal bleeding associated with angiodysplasia. Aliment Pharmacol Ther 2012; 36:587.

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For a discussion of thalidomide see here

Treatment of sclerosing mesenteritis

M Levin, MD — Fri, 24 Aug 2012 17:09:47 +0000

Sclerosing mesenteritis, also called mesenteric panniculitis, is a rare non-neoplastic disease that affects the small bowel mesentery with chronic fibrosing inflammation. Although a relatively benign condition, sclerosing mesenteritis can have a prolonged debilitating course with a fatal outcome. There are few data on the natural history and therapeutic options for this condition. Tamoxifen in combination with prednisone is the most common treatment, and most patients respond. I did not find any reports of the use of Rituxan.

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Octreotide for Small Bowel Obstruction

M Levin, MD — Thu, 09 Aug 2012 19:30:30 +0000

Malignant bowel obstruction (MBO) is a common and very difficult problem to manage at the end of the course of ovarian cancer, Surgery can help but is not always possible and often only temporarily effective. It should not be undertaken in patients known to have poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive ascites. Nasogastric drainage should generally only be a temporary measure and is nto comfortable. Self-expanding metallic stents are an option in malignant obstruction of the gastric outlet, proximal small bowel and colon. Medical treatment of pain and anuses can help. Soomatostatin analogues (e.g. octreotide) reduce gastrointestinal secretions and a number of reports over the last two decades confirm its limited but significant place in treating MBO. Octreotide can reduce secretions with or without anticholinergics , such as hyoscine hydrobromide. Octreotide can also diminish the hypertensive state in the lumen that causes the distension-secretion-distention cycle, which can lead to total obstruction if not treated.

Two randomized prospective studies were and a recent combination study with with metoclopramide, dexamethasone confirm octreotide effectiveness in MBO.

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Incivik

M Levin, MD — Thu, 09 Aug 2012 18:59:23 +0000

Telaprevir(Incivik) is the first hepatitis C drug that has demonstrated activity in patients who have failed prior therapy. In patients who received peginterferon alfa-2a and ribavirin for a year, the addition of telapravir for 24 weeks achieved a sustained virologic response(SVR) of 53% compared to 14% in patients who did not receive telapravir.It is thought that some patients who accomplish this outcome may be cured of Hepatitis, a feat rarely accomplished before. In a second randomized controlled trial (REALIZE) of patients who had previously relapsed or had only a partial response, rates of SVR were higher in patients treated with telaprevir (83% to 88%) compared to 24% in controls. In a third trial (ADVANCE) for previously untreated patients, patients taking telaprevir had a SVR (69% to 75%) versus 44% in the control group.

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