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CHICAGO — The incidence of the oldest side effect of anticancer treatment—diarrhea—is rising in parallel with the use of targeted agents, and clinicians need to manage this proactively in order to keep patients on treatment, said Dr. Joanna M. Brell of the Division of Cancer Prevention at the National Cancer Institute.
“Diarrhea occurs in about 80% of chemotherapy patients, and about 30% is grade 3/4 toxicity. It is common, it is associated with newer targeted therapies, it is additive with combination treatment, and patients are receiving treatment for longer periods. We'd better be good at managing it,” she told attendees at the annual Chicago Supportive Oncology Conference.
Diarrhea is a class effect of many older drugs and of the small-molecule agents that are approved in treating at least 10 malignancies, with many more compounds in the pipeline. (See box.) The fact that more targeted agents will be used in maintenance therapy means that more patients will experience diarrhea for longer periods of time, Dr. Brell warned.
The physical consequences include dehydration, electrolyte imbalance, acute renal failure, renal insufficiency, weight loss, malnutrition, and risk of infection. It causes generalized malaise, diminishes activities of daily living, enhances treatment noncompliance, and reduces quality of life. Importantly, an abnormal GI tract may affect absorption of oral chemotherapy, and dose reductions of anticancer drugs or discontinuations of treatment are sometimes required.
“Treatment delays have uncertain effects on the tumor, and this is distressing to the patient, who wants full treatment,” she said.
Why Diarrhea Occurs With Targeted Agents
The mechanisms by which diarrhea occurs with targeted agents were recently described (Nat. Clin. Pract. Oncol. 2008;5:268-78). They vary according to the class of agent.
With the epidermal growth factor receptor inhibitor erlotinib (Tarceva), the incidence—but not the severity—of diarrhea is dose related. Sorafenib (Nexavar), a multitargeted vascular inhibitor, causes diarrhea in 30%-43% of patients. This is thought to be related to small-vessel ischemia or ischemic colitis with mucosal changes, and to direct damage to mucosal cells. With bortezomib (Velcade), an NF kappaB inhibitor, diarrhea can have a relatively quick onset (with associated postural hypotension, syncope, or near-syncope) and can be dose limiting. Flavopiridol, which inhibits multiple cyclin-dependent kinases, enhances the efficacy of other chemotherapies. Cholestyramine can bind to flavopiridol and therefore protect against diarrhea, but how this may affect anticancer treatment is unknown, Dr. Brell said.
Management of Diarrhea Due to Targeted Agents
There is little to no evidence to guide the management of diarrhea that is specifically associated with targeted therapies, Dr. Brell said. Unlike conventional chemotherapy, the goal with these agents is not to increase response, and they are not dosed according to body surface area. The actual effective dose of the drugs, therefore, is generally unknown.
Given these considerations, the major management strategy with these agents is dose delay, she said. Brief dose interruptions are usually adequate, and the dose can usually be maintained in spite of the toxicity, “which we don't do with [5-fluorouracil] or irinotecan,” she noted. Dose reductions are done, if required, to maintain quality of life.
Cholestyramine can be tried for diarrhea that is associated with sorafenib, sunitinib (Sutent), and flavopiridol.
The usual management strategies also apply, added Dr. Brell. Clinicians should monitor stool output closely; stop supportive medications for constipation; use oral loperamide (Imodium) up to 16 mg/day, or diphenoxylate plus atropine (Lomotil) 5 mg two to four times per day; give intravenous fluids; rule out C. difficile; prescribe empiric antibiotics; and give octreotide (Sandostatin LAR Depot) 100 mcg three times daily, or at higher doses).
Clinicians should check for the use of medications that might increase diarrhea, such as CYP3A4 inhibitors that can affect drug metabolism such that levels of the anticancer therapy are increased and therefore toxicity is enhanced.
For prophylaxis, data are even more limited. Dr. Brell suggested trying cholestyramine prior to dosing sorafenib and sunitinib, giving octreotide LAR monthly, and giving octreotide and loperamide prior to chemoradiation to the pelvis.
The meeting was sponsored by Elsevier Oncology, a sister company to this news organization.
There is little to no evidence to guide the management of diarrhea due to targeted therapies.
Source DR. BRELL
Elsevier Global Medical News
CHICAGO — The incidence of the oldest side effect of anticancer treatment—diarrhea—is rising in parallel with the use of targeted agents, and clinicians need to manage this proactively in order to keep patients on treatment, said Dr. Joanna M. Brell of the Division of Cancer Prevention at the National Cancer Institute.
“Diarrhea occurs in about 80% of chemotherapy patients, and about 30% is grade 3/4 toxicity. It is common, it is associated with newer targeted therapies, it is additive with combination treatment, and patients are receiving treatment for longer periods. We'd better be good at managing it,” she told attendees at the annual Chicago Supportive Oncology Conference.
Diarrhea is a class effect of many older drugs and of the small-molecule agents that are approved in treating at least 10 malignancies, with many more compounds in the pipeline. (See box.) The fact that more targeted agents will be used in maintenance therapy means that more patients will experience diarrhea for longer periods of time, Dr. Brell warned.
The physical consequences include dehydration, electrolyte imbalance, acute renal failure, renal insufficiency, weight loss, malnutrition, and risk of infection. It causes generalized malaise, diminishes activities of daily living, enhances treatment noncompliance, and reduces quality of life. Importantly, an abnormal GI tract may affect absorption of oral chemotherapy, and dose reductions of anticancer drugs or discontinuations of treatment are sometimes required.
“Treatment delays have uncertain effects on the tumor, and this is distressing to the patient, who wants full treatment,” she said.
Why Diarrhea Occurs With Targeted Agents
The mechanisms by which diarrhea occurs with targeted agents were recently described (Nat. Clin. Pract. Oncol. 2008;5:268-78). They vary according to the class of agent.
With the epidermal growth factor receptor inhibitor erlotinib (Tarceva), the incidence—but not the severity—of diarrhea is dose related. Sorafenib (Nexavar), a multitargeted vascular inhibitor, causes diarrhea in 30%-43% of patients. This is thought to be related to small-vessel ischemia or ischemic colitis with mucosal changes, and to direct damage to mucosal cells. With bortezomib (Velcade), an NF kappaB inhibitor, diarrhea can have a relatively quick onset (with associated postural hypotension, syncope, or near-syncope) and can be dose limiting. Flavopiridol, which inhibits multiple cyclin-dependent kinases, enhances the efficacy of other chemotherapies. Cholestyramine can bind to flavopiridol and therefore protect against diarrhea, but how this may affect anticancer treatment is unknown, Dr. Brell said.
Management of Diarrhea Due to Targeted Agents
There is little to no evidence to guide the management of diarrhea that is specifically associated with targeted therapies, Dr. Brell said. Unlike conventional chemotherapy, the goal with these agents is not to increase response, and they are not dosed according to body surface area. The actual effective dose of the drugs, therefore, is generally unknown.
Given these considerations, the major management strategy with these agents is dose delay, she said. Brief dose interruptions are usually adequate, and the dose can usually be maintained in spite of the toxicity, “which we don't do with [5-fluorouracil] or irinotecan,” she noted. Dose reductions are done, if required, to maintain quality of life.
Cholestyramine can be tried for diarrhea that is associated with sorafenib, sunitinib (Sutent), and flavopiridol.
The usual management strategies also apply, added Dr. Brell. Clinicians should monitor stool output closely; stop supportive medications for constipation; use oral loperamide (Imodium) up to 16 mg/day, or diphenoxylate plus atropine (Lomotil) 5 mg two to four times per day; give intravenous fluids; rule out C. difficile; prescribe empiric antibiotics; and give octreotide (Sandostatin LAR Depot) 100 mcg three times daily, or at higher doses).
Clinicians should check for the use of medications that might increase diarrhea, such as CYP3A4 inhibitors that can affect drug metabolism such that levels of the anticancer therapy are increased and therefore toxicity is enhanced.
For prophylaxis, data are even more limited. Dr. Brell suggested trying cholestyramine prior to dosing sorafenib and sunitinib, giving octreotide LAR monthly, and giving octreotide and loperamide prior to chemoradiation to the pelvis.
The meeting was sponsored by Elsevier Oncology, a sister company to this news organization.
There is little to no evidence to guide the management of diarrhea due to targeted therapies.
Source DR. BRELL
Elsevier Global Medical News
CHICAGO — The incidence of the oldest side effect of anticancer treatment—diarrhea—is rising in parallel with the use of targeted agents, and clinicians need to manage this proactively in order to keep patients on treatment, said Dr. Joanna M. Brell of the Division of Cancer Prevention at the National Cancer Institute.
“Diarrhea occurs in about 80% of chemotherapy patients, and about 30% is grade 3/4 toxicity. It is common, it is associated with newer targeted therapies, it is additive with combination treatment, and patients are receiving treatment for longer periods. We'd better be good at managing it,” she told attendees at the annual Chicago Supportive Oncology Conference.
Diarrhea is a class effect of many older drugs and of the small-molecule agents that are approved in treating at least 10 malignancies, with many more compounds in the pipeline. (See box.) The fact that more targeted agents will be used in maintenance therapy means that more patients will experience diarrhea for longer periods of time, Dr. Brell warned.
The physical consequences include dehydration, electrolyte imbalance, acute renal failure, renal insufficiency, weight loss, malnutrition, and risk of infection. It causes generalized malaise, diminishes activities of daily living, enhances treatment noncompliance, and reduces quality of life. Importantly, an abnormal GI tract may affect absorption of oral chemotherapy, and dose reductions of anticancer drugs or discontinuations of treatment are sometimes required.
“Treatment delays have uncertain effects on the tumor, and this is distressing to the patient, who wants full treatment,” she said.
Why Diarrhea Occurs With Targeted Agents
The mechanisms by which diarrhea occurs with targeted agents were recently described (Nat. Clin. Pract. Oncol. 2008;5:268-78). They vary according to the class of agent.
With the epidermal growth factor receptor inhibitor erlotinib (Tarceva), the incidence—but not the severity—of diarrhea is dose related. Sorafenib (Nexavar), a multitargeted vascular inhibitor, causes diarrhea in 30%-43% of patients. This is thought to be related to small-vessel ischemia or ischemic colitis with mucosal changes, and to direct damage to mucosal cells. With bortezomib (Velcade), an NF kappaB inhibitor, diarrhea can have a relatively quick onset (with associated postural hypotension, syncope, or near-syncope) and can be dose limiting. Flavopiridol, which inhibits multiple cyclin-dependent kinases, enhances the efficacy of other chemotherapies. Cholestyramine can bind to flavopiridol and therefore protect against diarrhea, but how this may affect anticancer treatment is unknown, Dr. Brell said.
Management of Diarrhea Due to Targeted Agents
There is little to no evidence to guide the management of diarrhea that is specifically associated with targeted therapies, Dr. Brell said. Unlike conventional chemotherapy, the goal with these agents is not to increase response, and they are not dosed according to body surface area. The actual effective dose of the drugs, therefore, is generally unknown.
Given these considerations, the major management strategy with these agents is dose delay, she said. Brief dose interruptions are usually adequate, and the dose can usually be maintained in spite of the toxicity, “which we don't do with [5-fluorouracil] or irinotecan,” she noted. Dose reductions are done, if required, to maintain quality of life.
Cholestyramine can be tried for diarrhea that is associated with sorafenib, sunitinib (Sutent), and flavopiridol.
The usual management strategies also apply, added Dr. Brell. Clinicians should monitor stool output closely; stop supportive medications for constipation; use oral loperamide (Imodium) up to 16 mg/day, or diphenoxylate plus atropine (Lomotil) 5 mg two to four times per day; give intravenous fluids; rule out C. difficile; prescribe empiric antibiotics; and give octreotide (Sandostatin LAR Depot) 100 mcg three times daily, or at higher doses).
Clinicians should check for the use of medications that might increase diarrhea, such as CYP3A4 inhibitors that can affect drug metabolism such that levels of the anticancer therapy are increased and therefore toxicity is enhanced.
For prophylaxis, data are even more limited. Dr. Brell suggested trying cholestyramine prior to dosing sorafenib and sunitinib, giving octreotide LAR monthly, and giving octreotide and loperamide prior to chemoradiation to the pelvis.
The meeting was sponsored by Elsevier Oncology, a sister company to this news organization.
There is little to no evidence to guide the management of diarrhea due to targeted therapies.
Source DR. BRELL
Elsevier Global Medical News