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many chemotherapeutic agents including irinotecan , 5-fluorouracil , capecitabine , docetaxel , paclitaxel , doxorubicin , interferon , and gefitinib are commonly associated with diarrhea ( 1 ) .
the mechanism of chemotherapy induced diarrhea ( cid ) is not entirely understood but is believed to be primarily secretory , and may have an exudative component ( 2 ) .
main aims of standard guidelines for cid are to reduce the volume of diarrhea , to treat dehydration aggressively , and to use antibiotics if needed ( 2 , 3 ) . and in pharmacological managements , loperamide plays a main role ( 1 - 4 ) . but prophylaxis for cid is not well established .
docetaxel is a semi - synthetic taxane , with considerable activity against several types of solid tumors including breast , ovarian , gastric , prostate and non - small - cell lung cancers .
docetaxel binds to and stabilizes tubulin , thereby inhibiting microtubule disassembly which results in cell cycle arrest at the g2/m phase and cell death ( 5 ) .
frequent side effects of docetaxel include fluid retention , neurosensory events , alopecia , cutaneous events , stomatitis , nausea , vomiting , diarrhea , and neutropenia .
diarrhea develops in 20%-40% of patients with docetaxel - containing chemotherapy and severe diarrhea in 5%-6% ( 6 ) . in this report
, we describe a new prophylactic approach for the docetaxel induced diarrhea with loperamide in a patient with non - small - cell lung cancer .
a 72-yr old male patient was diagnosed with stage iv non - small - cell lung cancer ( nsclc ) in march 2012 .
he was treated with weekly docetaxel - cisplatin ( dp ) chemotherapy : docetaxel 35 mg / m and cisplatin 30 mg / m on day 1 and 8 every 3 weeks . during the 1st cycle , grade 3 nausea and vomiting developed from day 3 of chemotherapy .
thus fasting , parenteral nutritional support , and hydration with intravenous administration of metoclopramide and lorazepam were given . during the 2nd cycle , neither nausea nor vomiting but grade 3 diarrhea ( 8 - 10 stools per day ) developed from day 4 and he was admitted to hospital on day 6 .
grade 3 dehydration was combined while there was no abdominal pain , tenderness or fever .
laboratory examinations including white blood cell count , erythrocyte sedimentation rate , and c - reactive protein were within normal limits .
fasting , parenteral nutritional support and hydration with oral loperamide , starting with 4 mg followed by 2 mg every 2 hr , were done . despite of the management ,
diarrhea continued until day 9 of chemotherapy . on day 10 of his 2nd cycle ,
the same management with loperamide was done and the diarrhea was resolved on day 15 .
chemotherapy at day 8 of the 2nd cycle was delayed to day 16 and given with 20% reduced dose .
we concluded that docetaxel induced his diarrhea because of several reasons : no signs of infection , no use of antibiotics , repeated diarrhea after chemotherapy and little probability of diarrhea with other medications including dexamethasone , palonosetron and cisplatin .
chest computed tomography after 2 cycles of dp showed near complete response according to recist v 1.1 ( fig .
1 ) . thus we decided to continue dp chemotherapy despite of the severe repeated docetaxel induced diarrhea . on day 1 of the 3rd dp chemotherapy with 20% reduced dose , prophylactic loperamide ( 2 mg every 8 hr ) and fasting was started before administration of chemotherapy .
day 8 dp of 3rd cycle was delayed due to grade 2 asthenia and started on day 15 . on day 15 ,
the duration of fasting and administration of loperamide were shortened to 2 and 5 days , respectively .
subsequent cycles of dp chemotherapy with 20% reduced dose could be given without diarrhea by virtue of loperamide .
diarrhea is one of the most common side effects of chemotherapy and docetaxel is commonly associated with diarrhea .
cid can significantly affect the quality of life and may result fatal outcome either directly or indirectly from suboptimal therapy .
the pathogenesis of cid is unclear and the studies about cid have focused on irinotecan .
it is believed that toxicity to rapidly dividing crypt cells of the gut leads destruction and/or augmentation of intestinal enzymes .
this disturbs the balance between absorption and secretion , and alters the osmotic gap in the gut , thereby resulting increased secretion of fluids and electrolytes into the stool ( 4 , 7 ) .
recently , it has been suggested that alterations to intestinal tight junctions play a pivotal role in the pathogenesis of cid ( 8) . loperamide is an antidiarrheal agent with many actions of mechanisms : antisecretory , antiperistaltic effect inhibiting the calcium - binding protein calmodulin and direct effect on the gastrointestinal wall by interacting locally with neuronal mechanisms .
thereby , loperamide prolongs transit time , increases viscosity and bulk density , and reduces fecal volume and loss of fluids and electrolytes ( 9 , 10 ) . in treatment of cid ,
some guidelines recommend octreotide , a somatostatin analogue , for the prevention and the treatment of refractory cid ( 1 , 2 , 11 ) .
but octreotide is not easy to use due to the cost and the method of administration ( injection ) . in this patient ,
fasting and aggressive hydration with electrolyte supplements were started and loperamide was given for the management of cid .
the tumor response was excellent , thus dp chemotherapy was continued with the prophylactic approach .
oral loperamide with regimen of 2 mg every 8 hr successfully prevented docetaxel induced diarrhea .
the role of loperamide in the prophylaxis of cid requires further studies including appropriate dosing and duration .
rarely docetaxel induced colitis is reported and which is usually associated with acute abdominal pain , tenderness , febrile neutropenia , hemorrhagic diarrhea or oral stomatitis ( 12 , 13 ) .
the mechanism of the colitis is proposed : initial mucosal damage ; bacterial invasion ; secretion of bacterial endotoxins ; hemorrhage ; ulceration ; and ischemia , possible necrosis ( 14 ) . in this case
but clinicians should consider colitis in a patient with docetaxel induced diarrhea because the outcome of colitis can be fatal and the use of loperamide in that case can worsen the outcome . in conclusion , although further studies about the appropriate dosing and the schedule are required , we suggest oral loperamide as a prophylactic use in the cid : 2 mg every 8 hr from day 1 ( starting before chemotherapy ) to 5
. additionally , clinicians should concern the possibility of the docetaxel induced colitis when cid is suspicious .
diarrhea is a common adverse event of docetaxel with 20%-40% of incidence and severe diarrhea occurs in 5%-6% . 
 several treatment guidelines for chemotherapy induced diarrhea ( cid ) exist , however the prophylaxis for that is not well known . 
 we describe a new prophylactic approach for the cid with loperamide . a 72-yr - old male patient with stage 
 iv non - small - cell lung cancer developed diarrhea repeatedly after docetaxel - cisplatin chemotherapy . 
 his diarrhea persisted despite treatment including loperamide and fasting . 
 however , the diarrhea was successfully prevented when loperamide was given before and after the chemotherapy . to our knowledge , this is the first report of prophylactic approach for the cid with loperamide .