Capecitabine-induced paralytic ileus. Case report. Marinelli T., Carella A.M., Melfitano A., Di Pumpo M., Modola G., Conte M., Damone F., Florio C., P. De Luca, ...
XXIII Congresso Nazionale della Società Scientifica FADOI Bologna, 12-15 maggio 2018
Capecitabine-induced paralytic ileus. Case report. Marinelli T., Carella A.M., Melfitano A., Di Pumpo M., Modola G., Conte M., Damone F., Florio C., P. De Luca, Benvenuto A. Internal Medicine Department «T. Masselli-Mascia» Hospital, San Severo (Foggia) - Italy Background: Capecitabine (Figure1) is an oral prodrug of 5-fluorouracil (5-FU) commonly used in breast cancer as well in gastric and colorectal carcinomas; Capecitabine, inside the body, is converted to 5-FU through which it acts. Main metabolic pathways of Capecitabine are illustrated in Figure 2. Its most common adverse effects include abdominal pain, diarrhea, vomiting, weakness, and palmar-plantar erythrodysesthesia. Other severe side effects include blood clotting problems, allergic reactions, heart toxicity, and low blood cells count. In literature few cases of Capecitabine-induced paralytic ileus have been reported; however, paralytic ileus has been recognised as a potential side effect of capecitabine with an estimated incidence of 4% to 6%. Methods: we describe the case of a 61-year-old female receiving Capecitabine 1.500 mg daily, as chemotherapy regimen, after left hemicolectomy for colon carcinoma. At our observation the patient complained of diarrhea, vomiting and oliguria; we found arterial hypotension, sinusal tachycardia, dry skin and mucous membranes, swollen and slightly distended and painful abdomen with markedly torpid peristalsis.
Results: standard laboratory parameters showed neutrophilic leukocytosis, hyperazotemia (up to 184 mg/dL), high serum creatinine (up to 4.67 mg/dL), hyponatremia (127 mEq/L), hypokalemia (2.7 mEq/L) and severe metabolic acidosis. Abdominal radiography showed hydroaeric levels and gaseous intestinal distention, confirmed by abdominal computerised tomography, without signs of mechanical obstruction. Administration of Capecitabine was immediately halted, intestinal decompression was obtained by nasogastric tube and rectal probe; parenteral nutrition, hydro-electrolyte replacement and antibiotic therapy have allowed to reach, in 9 days, clinical improvement, recovery of intestinal peristalsis and complete normalization of laboratory alterations.
CAPECITABINE Figure1:
References Walko CM, et al. Capecitabine: a review. Clin Ther, 27:23-44, 2005.
Discussion: pathway and mechanisms of Capecitabine-induced paralytic ileus are not well clear; however, a transient motor/sensor neuropathy induced by 5-FU metabolites could be involved. Information regarding fluoropyrimidines and their effect on the enteric motor system is scant. Peripheral neuropathy has been reported with 5-FU given alone as well as when in combination with chemotherapy agents that are known to produce cumulative peripheral neuropathy such as platinum analogs and taxanes. Pharmacogenetic studies related to genes associated with 5-FU metabolism showed polymorphism of thymidylate synthase, one of target sites of 5-FU, possibly causing the nerve damage in these patients. A deterioration of a pre-existing latent paraneoplastic neuropathy, induced by Capecitabine, could also explain abdominal symptoms. However, compared to intravenous 5-FU, Capecitabine is associated with a lower incidence and severity of side effects, then it offers an easy alternative to its precursor. Conclusion: in cancer patients, this rare but severe side effect of Capecitabine must be considered for timely diagnosis and treatment. Neurological side effects should be borne in mind while administrating this class of drugs to patients. Dose adjustment and/or discontinuation must be assessed in any patient developing side effects to fluoropyrimidine therapies; while no evidence has been reported on the use of neostigmine in fluoropyrimidine -induced paralytic ileus. Acknowlegements:
Laudadio L, et al. Paralytic ileus associated with capecitabine. Tumori, 94: 742-5, 2008. Saif MW, et al. Peripheral neuropathy associated with capecitabine. Anticancer Drugs, 15: 76771, 2004.
Figure2:
Table2:
Table1:
