Sorafenib, a tyrosine kinase inhibitor with anti-angiogenic properties, is FDA-approved for the treatment of unresectable hepatocellular carcinoma (HCC), advanced renal cell carcinoma (RCC), and advanced differentiated thyroid carcinoma (DTC). As with any chemotherapeutic agent, its use comes with many potential side effects including hypertension, fatigue, pancytopenia, and electrolyte abnormalities.1 In addition to these adverse events, sorafenib has significant gastrointestinal (GI) toxicity, which, at its worst, can result in bowel perforation.

GI perforation is one of the most feared complications of sorafenib use and occurs in less than 1% of patients.1 Patients with GI perforation may complain of severe abdominal pain, fevers, chills, and decreased oral intake. On physical exam, the patient may be febrile, tachycardic, hypo- or hypertensive, tachypnic, and may have labile oxygen saturations.  They may appear toxic or septic, with a diffusely tender abdomen with decreased bowel sounds and rebound and/or guarding on physical exam.  If GI perforation were to occur, sorafenib should be permanently discontinued.1,2  In addition, supportive care with intravenous fluids and antibiotics, if warranted, as well as close monitoring of vital signs should be part of the patient’s management; possible surgical consultation should be considered. 

Some of the most common GI side effects of sorafenib include diarrhea (43%to 55%), abdominal pain (11% to 31%), nausea (23% to 24%), vomiting (15% to 16%), elevated lipase (40% to 41%), elevate amylase (30% to 34%), and weight loss (10% to 30%).1 As a patient continues to take sorafenib, there may be a component of cumulative toxicity secondary to chronic use.3

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Sorafenib has anti-angiogenic properties that can help reduce blood flow to tumors; however, these anti-angiogenic properties can also do the same to normally functioning organs and tissue. One such organ that may be affected by reduced blood flow is the pancreas, which over time, can become atrophic, and lead to worsening side effects including diarrhea and abdominal pain.3 There are limited data that suggests extended use of sorafenib (eg, more than 24 months and/or more than 1,000 g) is associated with pancreatic atrophy, leading to steatorrhea and the need for exogenous pancreatic enzyme supplementation. Steatorrhea in patients on sorafenib can be treated with oral pancreatic enzyme repletion, along with a dose reduction or temporary discontinuation.2,4

Sorafenib plays an important role in the treatment of HCC, RCC, and DTC. GI toxicity is an important factor in the ability of the patient to tolerate treatment, as well as in their long-term outcome, and should therefore be closely monitored. 

References

  1. Sorafenib [prescribing information]. Whippany, NJ:. Bayer HealthCare Pharmaceuticals, Inc.
  2. Hutson TE, Figlin RA, Kuhn JG, et al. Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies. Oncologist. 2008;13(10):1084-1096.
  3. Hescot S, Vignaux O, Goldwasser F. Pancreatic atrophy—a new late toxic effect of sorafenib. N Engl J Med. 2013;369(15):1475-1476.
  4. Mir O, Coriat R, Boudou-Rouquette P, et al. Sorafenib-induced diarrhea and hypophosphatemia: mechanisms and therapeutic implications. Ann Oncol. 2012;23(1):280-281.

Topics:

Gastrointestinal Cancer In The Clinic Renal Cell Carcinoma Thyroid Cancer