Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER)
BackgroundAlternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer.Patients and methodsEligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival.ResultsOf 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75–88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7–9.5 months). The median overall survival was 23.1 months (95% CI 17.4–28.8 months). The response rate was 44% (95% CI 30.2–57.8%), and the disease control rate was 88% (95% CI 79.0–97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events.ConclusionS-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.
Retrospective Analysis of S-1 plus Bevacizumab as Maintenance Therapy after Induction of S-1 and Oxaliplatin (SOX) plus Bevacizumab as First-Line Chemotherapy in Patients with Metastatic Colorectal Cancer
Background: 
The SOFT study was a phase III trial designed to validate the non-inferiority of S-1 and oxaliplatin (SOX) plus 
bevacizumab to mFOLFOX6 plus bevacizumab in terms of PFS in patients 
with metastatic colorectal cancer (mCRC) who had not previously received 
chemotherapy. In this study, we retrospectively reviewed cases in which S-1 
plus bevacizumab as maintenance therapy after induction of S-1 and Oxaliplatin 
(SOX) plus bevacizumab as first-line chemotherapy in patients with metastatic 
colorectal cancer was applied in order to evaluate its efficacy and safety in 
clinical practice. Material and method: Among the 40 patients with mCRC at the 
Fuchu Hospital who received SOX plus bevacizumab 
as a first line treatment between August 2013 and December 2018. The eligible 
patients had histologically confirmed mCRC. On day 1 of each 3-week period during the study, 
patients in the SOX plus bevacizumab received a 7.5 mg/kg intravenous infusion 
of bevacizumab, followed by an intravenous infusion of 130 mg/m2 oxaliplatin. 
S-1 (40 - 60 mg) was 
administered orally two times per day from after dinner on day 1 to after breakfast on day 15, followed by a 7-day rest. Results: The median PFS was 15.0 months and median OS was 
36.0 months. The response rate (RR: complete pus partial response) was 85.0%, 
and the disease control rate (DCR: RR plus stable disease) was 92.5%. The most common adverse 
events with SOX plus bevacizumab were hypertension (50%), neurosensory toxicity 
(50%), anorexia (32.5%), fatigue (45%), 
pigmentation (39%), Neutrophil count decreased (30%), and platelet count decreased (40%). The most 
common grade 3/4 adverse events were 
neurosensory toxicity (5%) and fatigue (9%). Conclusion: This study revealed that 
the survival benefit of S-1 and oxaliplatin (SOX) plus bevacizumab in Japanese 
patients with mCRC was like that observed in previous clinical trials. 
Therefore, S-1 and oxaliplatin (SOX) plus bevacizumab can be considered as 
routine first-line treatment option for patients with mCRC.
Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition.
OBJECTIVE
The authors characterize the recovery of parenteral nutrition-induced changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract immunity with enteral nutrition and provide further information defining the effects of enteral feeding on mucosal immunity.


SUMMARY BACKGROUND DATA
The small intestine plays a prominent role in development and maintenance of mucosal immunity, both intestinal and extraintestinal, primarily through immunoglobulin A (IgA)-mediated mechanisms. Prior research has shown that mice fed total parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible for IgA production, as well as impaired upper respiratory tract immunity to viral challenge of previously immunized animals. The recovery of TPN-induced changes in GALT and upper respiratory tract immunity after enteral refeeding is studied.


METHODS
Male institute of Cancer Research mice received 5 days of TPN followed by 0 to 4 days of chow. Small intestinal GALT was characterized by flow cytometry. In a second experiment, animals were immunized intranasally with moused-adapted influenza virus. Three weeks later, one group received a 5-day course of TPN followed by enteral refeeding for 5 days. A second group received TPN alone. Both groups were challenged with intranasal virus and killed 40 hours postchallenge to determine viral shedding from the upper respiratory tract.


RESULTS
Animals fed TPN only had significantly fewer GALT lymphocytes compared with those chow-fed control subjects. Peyer's patch counts increased after a single day of refeeding, returning to normal levels by 48 hours. Lamina propria counts remained significantly depressed after 24 hours of refeeding, but also returned to normal after 48 hours of refeeding. The T-cell and B-cell populations mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal only after 72 hours of refeeding. None of the 9 animals refed enterally for 5 days were positive for viral shedding, compared with 8 of 12 matched TPN-fed animals.


CONCLUSIONS
Enteral refeeding after TPN is associated with rapid repletion of GALT cellularity, initially within Peyer's patches and subsequently within the lamina propria. Refeeding corrects the impairment of IgA-mediated upper respiratory tract antiviral immunity occurring with TPN administration. This work further enhances the authors' knowledge of the underlying immunologic differences influenced by routes of nutrition.