Survival Benefit of Neoadjuvant Chemotherapy for Locally Advanced Adenocarcinoma of Esophagogastric Junction

Background/Aim: Adenocarcinoma of the esophagogastric junction (AEG) is refractory even when curative resection is followed by adjuvant chemotherapy. This study evaluated the efficacy of neoadjuvant chemotherapy (NAC) using an oral fluoropyrimidine-platinum regimen for AEG. Patients and Methods: Out of 35 patients with locally advanced AEG who underwent curative resection, 21 who underwent surgery first and 14 who received NAC were retrospectively compared in terms of survival. Results: The NAC regimens comprised of S-1 or capecitabine plus oxaliplatin or cisplatin; trastuzumab was added to six borderline resectable cases. The downstaging rate was 50% and the pathological response rate including complete response (29%) was 50%. The three-year relapse-free survival in the NAC group was significantly superior than the surgery-first group (78% vs. 22%, p=0.011). The NAC group had a significantly longer median survival time than the surgery-first group (NR vs. 29 months, p=0.032). Conclusion: NAC using an oral fluoropyrimidine-platinum regimen may provide survival benefit in AEG.

Small intestinal mucosal injury and its risk factors in patients with gastrointestinal cancer who developed complicated fluoropyrimidine-induced diarrhea

Background Diarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, limited data are available on the frequency and risk factors of complicated chemotherapy-induced diarrhea (CID) and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE) and determined baseline risk factors associated with complicated CID. Methods In total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID. Results Total number of 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 25 (78%) patients, with cramping, vomiting, and sepsis being observed in 15 (60%), 8 (32%), and 3 (12%) patients, respectively. Among the 13 patients who underwent CE, 11 (85%) showed abnormal findings. Multivariate analysis revealed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio 2.95; 95% confidence interval 1.06–8.19). Conclusions Despite the relatively low incidence of complicated CID, mucosal injury of small intestine was common in patients with complicated fluoropyrimidine-induced diarrhea and oral fluoropyrimidine was an independent risk factor.

Small intestinal mucosal injury and its risk factors in patients with gastrointestinal cancer who developed complicated fluoropyrimidine-induced diarrhea

Background: Diarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, limited data are available on the frequency and risk factors of complicated chemotherapy-induced diarrhea (CID) and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE) and determined baseline risk factors associated with complicated CID.Methods: In total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID.Results: Total number of 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 25 (78%) patients, with cramping, vomiting, and sepsis being observed in 15 (60%), 8 (32%), and 3 (12%) patients, respectively. Among the 13 patients who underwent CE, 11 (85%) showed abnormal findings. Multivariate analysis revealed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio, 2.95; 95% confidence interval, 1.06–8.19).Conclusions: Despite the relatively low incidence of complicated CID, mucosal injury of small intestine was common in patients with complicated fluoropyrimidine-induced diarrhea and oral fluoropyrimidine was an independent risk factor.

Impact of the prior chemotherapy with two different fluoropyrimidines on the efficacy of CapeIRI or FOLFIRI in metastatic colorectal cancer: An exploratory analysis of the phase III AXEPT trial.

711 Background: Modified CapeIRI (irinotecan 200 mg/m2 on day 1, capecitabine 1600 mg/m2 on days 1–14 every 3 weeks) with or without bevacizumab (± BV) has shown non-inferiority of overall survival compared with FOLFIRI ± BV based on the phase III study, AXEPT, as second-line chemotherapy for patients with mCRC. In this exploratory analysis of the AXEPT trial, we evaluated the impact of the prior chemotherapy with two different fluoropyrimidine backbones (fluorouracil and leucovorin vs oral fluoropyrimidine) on the efficacy of CapeIRI and FOLFIRI. Methods: Patients were randomized to receive standard FOLFIRI ± bevacizumab or modified CapeIRI ± bevacizumab after failure to fluoropyrimidine-based chemotherapy in the AXEPT study. Prior fluoropyrimidine backbones were categorized into oral fluoropyrimidine-based (eg, capecitabine or S-1) regimen (oral 5-FU group) and fluorouracil and leucovorin-based regimen (infusional 5-FU group). Assessed endpoints included overall survival, progression-free survival, response rate, and safety. Results: Prior fluoropyrimidine backbone was available for 642 patients among all 650 randomized patients (oral 5-FU group in 291, and infusional 5-FU group in 351). Median overall survival was 17.0 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 14.9 and 16.7 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Median progression-free survival was 7.9 and 8.6 months for FOLFIRI ± BV and CapeIRI ± BV in the prior oral 5-FU group, and 6.8 and 8.3 months for FOLFIRI ± BV and CapeIRI ± BV in the prior infusional 5-FU group. Conclusions: There was no significant difference in the efficacy of CapeIRI or FOLFIRI regardless of prior fluoropyrimidine backbones. Therefore, CapeIRI ± BV could also be effective for patients after failure of oral fluoropyrimidine-based chemotherapy (eg, CapeOX ± BV). Clinical trial information: NCT01996306. [Table: see text]

Capecitabine-Associated Terminal Ileitis

Capecitabine is an oral fluoropyrimidine used as adjuvant and palliative chemotherapy in patients with colorectal cancer. Diarrhea is a well-known side effect of capecitabine and 5-fluorouracil agents. We present a case with terminal ileitis as a rare adverse event of capecitabine treatment. Capecitabine-induced terminal ileitis is likely to be underreported. It should be considered more often as a cause of severe and atypical complaints of diarrhea during treatment with capecitabine or other 5-fluorouracil agents.