The Assessment and Management of Cancer Treatment–Related Diarrhea

O'Brien, Bridget; Kaklamani, Virginia; Benson, Al B.

doi:10.3816/ccc.2005.n.009

Cited by 32 publications

(20 citation statements)

References 19 publications

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“…Gastrointestinal adverse events, including diarrhea, nausea and vomiting were commonly reported for these multikinase inhibitors. Although these events might not lead to treatment discontinuation and can be properly managed by pharmacological intervention and dietary modifications, in elderly patients, these events might lead to serious dehydration if they are not well controlled (29). Previous studies also reported that treatment-related diarrhea can be persistent for the duration of multikinase therapy and mild-to-moderate diarrhea can reduce the mobility and independence of patients, impairing quality of life (30)(31)(32).…”

Section: Sternberg 2010 ---------------------------------------------mentioning

confidence: 99%

Therapeutic effects and associated adverse events of multikinase inhibitors in metastatic renal cell carcinoma: A meta-analysis

Tan

Long²,

Chen

2015

Experimental and Therapeutic Medicine

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Abstract. This study aimed to compare the therapeutic effects and adverse events of the multikinase inhibitors sorafenib, sunitinib, pazopanib and axitinib in advanced renal cell carcienal cell carcinoma (RCC). A meta-analysis of randomized controlled trials was performed to assess the effects of multikinase inhibitors among patients with advanced RCC. The data of median progression-free survival (PFS), median overall survival (OS), progressive disease rate (PDR), objective response rate (ORR) and grade 3/4 adverse events were extracted to assess therapeutic effects and toxicity, respectively. It was found that multikinase inhibitors are more effective in extending PFS [hazard ratio (HR)= 0.58; 95% confidence interval (CI): 0.45-0.74; P<0.0001), controlling tumor progression [relative risk (RR)=0.67; 95% CI: 0.55-0.83; P=0.0002) and ORR (RR=2.93; 95% CI: 1.40-6.14; P=0.004) compared with placebo or interferon-α. Patients treated with multikinase inhibitors had significantly higher rates of grade 3 or 4 hypertension (RR=6.00; 95% CI: 3.36-10.69; P<0.00001), diarrhea (RR=5.84; 95% CI: 3.06-11.16; P<0.00001), nausea (RR=2.30; 95% CI: 1.16-4.54; P=0.02), vomiting (RR=1.84; 95% CI: 1.00-3.41; P=0.05) and hand-foot skin reaction (RR=11.78; 95% P<0.00001). Multikinase inhibitors can significantly control disease progress and improve the ORR. However, they are also associated with a higher risk of grade 3 and 4 hypertension and gastrointestinal events. Proper management of these events is necessary to improve patient quality of life.

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Section: Sternberg 2010 ---------------------------------------------mentioning

confidence: 99%

Therapeutic effects and associated adverse events of multikinase inhibitors in metastatic renal cell carcinoma: A meta-analysis

Tan

Long²,

Chen

2015

Experimental and Therapeutic Medicine

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“…Treatment recommendations for lapatinib-associated diarrhea are not evidence based but management recommendations are similar to those that are given for capecitabine-associated diarrhea. If a patient experiences mild-to-moderate (grade-1 or -2) diarrhea, they should generally avoid all lactose-containing products, stay well hydrated, eat frequent small meals and administer antidiarrheals, such as loperamide [40,41]. The dosage of loperamide should be an initial dose of 4 mg followed by 2 mg every 4 h or after every unformed stool, and should be continued until the patient is free from diarrhea for at least 12 h. If diarrhea is moderate or severe, or there are complicating features, such as severe cramping, severe nausea or vomiting, fever or dehydration, further doses of lapatinib should be held and intravenous fluids and inpatient hospitalization should be considered.…”

Section: Side Effect Managementmentioning

confidence: 99%

Lapatinib and breast cancer: current indications and outlook for the future

Moreira

Kaklamani

2010

Expert Review of Anticancer Therapy

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Lapatinib is an oral dual erbB 1/2 tyrosine kinase inhibitor that inhibits human EGF receptor 2 (HER2) and blocks the EGF receptor. Studies have shown that in patients with metastatic HER2-positive breast cancer that is resistant to trastuzumab, the addition of lapatinib to capecitabine improves progression-free survival and appears to lengthen overall survival. Furthermore, lapatinib has been studied in patients with involvement of the CNS and has been associated with stable disease and some responses. Its combination with letrozole provided an improvement in progression-free survival compared with single-agent letrozole in women with hormone receptor-positive, HER2-positive metastatic breast cancer. More recently, data suggested that the combination of lapatinib with trastuzumab significantly improves overall survival in women with metastatic breast cancer compared with single-agent lapatinib. Current indications in the USA for the use of lapatinib are for the treatment of metastatic HER2-positive breast cancer, both in combination with capecitabine in patients who have received taxane, anthracycline and traztuzumab, and in combination with letrozole for postmenopausal patients with hormone receptor- and HER2-overexpressing breast cancer. Common side effects of lapatinib include diarrhea and rash. Studies to date have found a less than 2% risk for cardiotoxicity, although most cardiac events that occurred during the studies were not attributed to lapatinib. It is important to consider that most of the patients in existing studies had already been treated with trastuzumab with no significant cardiotoxicity; therefore, future studies will show how trastuzumab-naive patients tolerate lapatinib. Ongoing research is evaluating the role of lapatinib in the adjuvant setting as a single agent or in combination with trastuzumab.

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“…16,17 Severe toxicity associated with 5-FUcontaining chemotherapy regimens can occasionally result in prolonged hospitalization and can limit both the duration and intensity of effective cancerdirected therapy. 18,19 Pre-treatment detection of patients at risk of toxicity would enable timely reduction or selection of alternative treatment modalities. This study investigated the relationship between the plasma UH 2 /U ratio, a surrogate marker of DPD activity, and 5-FU-related early toxicity.…”

Section: Introductionmentioning

confidence: 99%

The Value of Dihydrouracil/Uracil Plasma Ratios in Predicting 5-Fluorouracil-Related Toxicity in Colorectal Cancer Patients

Kristensen¹,

Pedersen²,

Mejer

2010

J Int Med Res

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This study investigated the relationship between the dihydrouracil/uracil (UH(2)/U) plasma ratio, a surrogate marker of dihydropyrimidine dehydrogenase (DPD) activity, and 5-fluorouracil (5-FU)-related early toxicity. Plasma UH(2)/U ratios were determined in 68 colorectal cancer patients and 100 healthy controls. A cut-off value indicative of DPD deficiency was calculated using receiver operator characteristics. Patients experiencing toxicity were screened for the DPD G-to-A point mutation within the 5'-splicing donor site of intron 14 (IVS14+1G>A). Overall, 24/68 patients (35%) experienced toxicity (all grades) and abnormal UH(2)/U ratios were demonstrated in 21/24 (87.5%) patients. Drug concentrations up to 130 times the recommended level were found in 13/24 (54%) patients experiencing toxicity. One patient experiencing toxicity was a heterozygous carrier of the IVS14+1G>A mutation. A low UH(2)/U plasma ratio had a sensitivity of 0.87 and specificity of 0.93 for predicting 5-FU-induced toxicity. Systematic detection of DPD-deficient patients using the UH(2)/U ratio could optimize 5-FU-based chemotherapy and minimize life-threatening toxicity.

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The Assessment and Management of Cancer Treatment–Related Diarrhea

Cited by 32 publications

References 19 publications

Therapeutic effects and associated adverse events of multikinase inhibitors in metastatic renal cell carcinoma: A meta-analysis

Therapeutic effects and associated adverse events of multikinase inhibitors in metastatic renal cell carcinoma: A meta-analysis

Lapatinib and breast cancer: current indications and outlook for the future

The Value of Dihydrouracil/Uracil Plasma Ratios in Predicting 5-Fluorouracil-Related Toxicity in Colorectal Cancer Patients

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