Recommended Guidelines for the Treatment of Cancer Treatment-Induced Diarrhea

Benson, Al B.; Ajani, Jaffer A.; Catalano, Robert B.; Engelking, Constance; Kornblau, Steven M.; Martenson, James A.; McCallum, Richard W.; Mitchell, Edith P.; O'Dorisio, Thomas M.; Vokes, Everett E.; Wadler, Scott

doi:10.1200/jco.2004.04.132

Cited by 529 publications

(467 citation statements)

References 33 publications

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“…Administration of this drug, however, causes 2 forms of diarrhea, an early cholinergic diarrhea and a severe delayed diarrhea, both of which are distressing to patients and can cause disruptions in treatment. 4,5 Previous research has proposed varying mechanisms for the delayed-onset diarrhea, [6][7][8][9] but the definitive mechanism behind this remains unknown. It has been previously shown that irinotecan differs from most cytotoxic agents in that it causes severe gastrointestinal damage with increased apoptosis in both the small and large intestines, changes in intestinal morphometry and excessive mucus secretion in the colon.…”

mentioning

confidence: 99%

Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor‐bearing DA rats

Gibson

Bowen

Keefe

2005

Intl Journal of Cancer

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Mucositis is a common side effect of cancer chemotherapy for which there is currently no treatment. Irinotecan is a commonly used effective chemotherapeutic agent, causing severe gastrointestinal mucositis and diarrhea. Previous research suggests that palifermin is potentially antimucotoxic. The primary aim of this study was to determine whether palifermin was effective in ameliorating irinotecan-induced gastrointestinal mucositis. We also determined the protective effects of single large and multiple small doses of palifermin. Tumor-bearing DA rats were treated with a single large (10 mg/kg) dose of palifermin 3 days prior to, or multiple small (3 mg/kg day for 3 days) doses of palifermin or vehicle control prior to, receiving 2 doses of 150 mg/kg irinotecan. Animals were killed at 6, 24, 48, 72, 96, 120, or 144 hr after treatment. The primary endpoints were diarrhea and mortality. Gastrointestinal morphometry, histopathology and apoptosis were assessed. Tumor weights and mitoses were measured to ensure palifermin did not promote tumor growth. Data were analyzed using Peritz' F-test, Student's t-test and Tukey-Kramer multiple comparison test. Animals pretreated with palifermin tolerated irinotecan treatment better than control animals with less severe diarrhea (5% in animals receiving 10 mg/kg palifermin, 11% in animals receiving 3 3 3 mg/kg palifermin and 28% in animals receiving irinotecan only) and reduced mortality (2% in animals receiving 10 mg/kg palifermin, 11% in animals receiving 3 3 3 mg/kg palifermin and 28% in animals receiving irinotecan only). Small and large intestinal weights were maintained. Intestinal morphometry was not maintained in palifermin-pretreated rats despite being increased prior to irinotecan treatment. Palifermin pretreatment did not prevent apoptosis that peaked at 6 hr in the jejunum or colon, but prevented apoptosis at 96 hr in the small intestine. Palifermin pretreatment in both treatment regimens significantly reduces diarrhea and mortality following irinotecan administration without adversely affecting tumor growth. This positive response warrants further investigation, particularly in humans. ' 2005 Wiley-Liss, Inc.Key words: mucositis; irinotecan; palifermin; diarrhea Mucositis is a major oncologic problem caused by the cytotoxic effects of cancer chemotherapy. The condition affects the entire gastrointestinal tract from the mouth to the anus and causes pain and ulceration in both the mouth and small and large intestines. In addition, it causes abdominal bloating, vomiting and diarrhea.

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confidence: 99%

Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor‐bearing DA rats

Gibson

Bowen

Keefe

2005

Intl Journal of Cancer

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“…Most drug toxicity can be managed with appropriate use of urea based creams and topical emollients, antiemetics, and antidiarrhea medication. 27,28 Efficacy should be documented with imaging. Computed tomography or magnetic resonance imaging of the chest, abdomen, and pelvis to include areas of active disease should be performed at regular intervals.…”

Section: Monitoring Of Therapymentioning

confidence: 99%

“…In general, Child-Pugh B patients treated with sorafenib do not live as long as patients with Child-Pugh A, but Table adapted from sorafenib package insert for managing skin toxicities. Treatment strategies for managing skin toxicity and diarrhea can be found in Lacouture et al 27 and Benson et al, 28 respectively. that could very well reflect the natural history of their liver disease rather than a difference in anticancer activity of sorafenib.…”

Section: Areas Of Uncertaintymentioning

confidence: 99%

Drug therapy: Sorafenib

Finn

2010

Hepatology

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A 72-year-old active male patient with cirrhosis secondary to nonalcoholic steatohepatitis is evaluated for liver masses. He has no stigmata of end-stage liver disease such as ascites, icterus, or hepatic encephalopathy on physical examination. Laboratory values include a hemoglobin of 12 g/dL with a mean corpuscular volume of 98, white cell count of 3.9 thousand, platelet count of 76,000, total bilirubin of 1.2 mg/dL, albumin of 3.5 g/dL, international normalized ratio of 1.2, and serum creatinine of 1.3 mg/dL. The alpha-fetoprotein is 620 ng/mL. The computed tomographic scan of the abdomen shows two masses in the right lobe of the liver and three in the left lobe, all with arterial enhancement. The largest mass is 4 cm in diameter and appears to invade the portal vein; the liver appears cirrhotic but there is no ascites.

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“…In vitro studies have shown that telmisartan acts as a partial agonist of PPARg and modulates the expressions of PPARg target genes involved in carbohydrate and lipid metabolism. 16 One report suggests that telmisartan, in contrast to some other ARBs, may exert additional effects through activation of PPARg. 17 Telmisartan induces adiponectin expression via PPARg activation 18 and proliferates human endothelial progenitor cells via a PPARg-dependent PI3K/Akt signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Effects of telmisartan and losartan on cardiovascular protection in Japanese hypertensive patients

et al. 2011

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The Telmisartan and Losartan Cardiac Evaluation Trial, a multicenter, prospective, randomized, open-labeled, blinded-endpoint trial, was designed to compare the effects of two angiotensin II receptor blockers (ARBs), telmisartan and losartan, on cardiovascular protection in Japanese patients with mild to moderate essential hypertension. We compared the effects of telmisartan and losartan on left ventricular (LV) hypertrophy, cardiac function, atherosclerosis of carotid arteries and surrogate markers related to the actions of peroxisome proliferator-activated receptor-c. A total of 58 patients were enrolled in the present trial and the follow-up period was 1 year. There were no significant differences in blood pressure (BP) levels between the telmisartan group and the losartan group throughout the trial. The percentage of the patients treated with ARB monotherapy was significantly higher in the telmisartan group compared with the losartan group. In addition, the progression of intima-media thickness of common carotid artery was significantly inhibited in the telmisartan group compared with the losartan group. Neither group experienced significant changes in cardiac function and LV mass index. There were no differences between the groups with respect to changes in surrogate markers such as serum adiponectin, creatinine, homeostasis model assessment index, plasminogen activator inhibitor-1 and high sensitivity C-reactive protein. Although BP levels were equal and well controlled in both groups, telmisartan showed more protective vascular effects than losartan.

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Recommended Guidelines for the Treatment of Cancer Treatment-Induced Diarrhea

Abstract: With vigilant monitoring and aggressive therapy for cancer treatment-induced diarrhea, particularly in patients with early warning signs of severe complications, morbidity and mortality may be reduced.

Cited by 529 publications

References 33 publications

Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor‐bearing DA rats

Palifermin reduces diarrhea and increases survival following irinotecan treatment in tumor‐bearing DA rats

Drug therapy: Sorafenib

Effects of telmisartan and losartan on cardiovascular protection in Japanese hypertensive patients

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