Naslov
Acute ileitis induced by capecitabine: literature review and case report

Autori
Jurčić, Petra.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, stručni

Izvornik
Abstract book / Bilić, Ivan ; Vrbanec, Damir - , 2016, 68-69

Skup
8th Symposium and annual meeting of Croatian society for medical oncology with international participation

Mjesto i datum
Trakošćan, Hrvatska, 21.10.2016. - 23.10.2016

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
acute ileitis ; capecitabine ; DPD testing

Sažetak
Multicenter randomized X-ACT trial compared oral capecitabine (CAP) with bolus i.v. 5-fluorouracil (5-FU)/folinic acid (FA) as adjuvant therapy for stage III colon cancer. CAP was not statistically inferior to the 5-FU for disease-free survival (DFS). Safety data from the X-ACT trial, showed that CAP had an improved safety profile compared with bolus 5-FU/FA in terms of significantly lower rates of diarrhea, stomatitis, nausea, alopecia, neutropenia, and febrile neutropenia ; CAP was, however, associated with significantly more hand–foot syndrome (HFS) than 5-FU/FA.1 The study data was owned by the sponsor and included only patients with Dukes C colon cancer. A 73-year-old female patient with a family history of lung cancer in her mother, a history of hepatitis B infection and surgical treatment of venous insufficiency of the left lower extremity has since spring 2015 suffered from intermittent hematochezia that she attributed to hemorrhoids. On June 29th 2015 the patient was hospitalized for ileus in Nova Gorica, Slovenia and underwent urgent subtotal colectomy, splenectomy and ileostomy formation. Preoperative abdominal and pelvic computed tomography (CT) scans, as well as chest radiograph showed no dissemination. Preoperative carcinoembryonic antigen (CEA) level was normal. On pathological examination, the tumor was diagnosed as moderately differentiated adenocarcinoma of the sigmoid colon with less than 50% mucous structures, stage pT3N0M0, without perforation, lymphocyte infiltration, and lymphovascular invasion present, no perineural invasion, R0. Two weeks after starting CAP as first line chemotherapy at a dose of 1, 250 mg/m2 administered orally twice daily (total daily dose 3000 mg) for 2 weeks followed by a 1 week rest period given as 3 week cycles, she presented to the Emergency department with grade 4 diarrhea, severe performance status alteration and fatigue. On admission she had a blood pressure of 55/40 mmHg in the supine position with a pulse rate of 105 per minute and respiratory rate of 16 per minute. Pulse oximetry (SpO2) showed 95 % on room air. She was afebrile, conscious, and anxious, with pale skin and mucous membranes with coated tongue and cold sore on lower lip. Her abdomen was nontender, revealed a midline scar and a stoma in the right lower quadrant with watery stool (mean 4 liter) in a stoma bag. Her urine output has been only 10cc an hour for the last 6 hours. Initial laboratory studies were: hemoglobin = 9.5 g/dL, hematocrit = 28.4 % ; WBC = 15, 600 (N-3, 400-9, 700) ; Na++=128 mEq/1 (N-137-146) ; K+5.1 mEq/1 (N-3.5-5.0) ; Cl-83 mEq/1(N-97-108) ; Anion gap 29.3 mEq/1 (N-8-16), BUN 57.69 mg/dL (N-7-19) ; Creatinine 6.76 mg/dL (N-0.7-1.4) ; Capillary blood gases-pH 7.30 (N-7.35-7.45) ; PaO2 83mmHg (N-75-100) ; PaCO2 30 mmHg (N-38-42) ; HCO3 15 mEq/1 (N-16-24) ; Base excess-2 ; urine sp. gr. 1.030 (N-1.003-1.025) ; urine pH 6.0 (N-4.6-8.0). Treatment consisted of parenteral rehydration and electrolyte replacement, correction of metabolic acidosis, hypoglycaemia and secondary anemia. Stool for Clostridium difficile, parasites and culture were all negative. Loperamide therapy did not reduce the stool volume within the first 48 hours. On the 3rd day of the patient’s hospital stay octreotide drip was started (maximum daily dose of 1500 mg was administered intravenously via 24-hour infusion over 4-day period), along with a modified diet and limited peroral fluid intake. Following this treatment the stool volume was reduced, which prompted a gradual reduction of octreotide dose (1200-1000-750-0 mg) and an increase in peroral semi-elemental formula intake. On the 11th day the patient was discharged for hospital in good general condition. The dihydropyrimidine dehydrogenase (DPD) mutation test (c.496A>G, c.1679T>G, c.2846A>T, c.1236G>A, IVS14+1G>A) was negative. A histopathology report after follow up colonoscopy 2 months later showed increased enterocyte apoptosis and loss of intestinal villi. Pathobiology of 5-FU related diarrhea is not understood. The data from animal studies suggests that mitotic arrest of intestinal crypt cells and decrease of the relative fraction of villous enterocytes. The median time to first occurrence of grade 2-4 diarrhea is 34 days, and the median duration is about five days. According to FDA report, only 19 patients were reported with ileitis as a side effect of CAP therapy. Reviewing of the literature by using PubMed and Ovid database has shown only nine reported cases of ileitis as a side effect of CAP therapy. Three reported cases were related to adjuvant setting therapy, one to neoadjuvant setting, and five to metastatic setting. The male-female ratio was 5:4. The median age of patients was 65 years. In two patients, ileitis occurred during the first cycle (as in my patient). Radiological diagnosis of the disease was established in seven patients, while histopathological diagnosis confirmed the disease in four cases. In all cases, conservative treatment was performed. None of the patients received octreotide, although it has a role in the guidelines for management of chemotherapy induced diarrhea. In four cases, DPD testing was performed, as was in the case presented here. Two test results were positive, and two were negative.2, 3, 4, 5, 6, 7, 8 Nevertheless, negative results in DPD testing do not exclude mutation of DPYS, TYMS, MTHFR, CDA genes. Ileitis may occur despite previous good tolerance to capecitabine. A high index of suspicion is crucial for prompt diagnosis. Ileitis may be reversible with early recognition, close monitoring and proper supportive treatment.

Izvorni jezik
Engleski

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Kliničke medicinske znanosti

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