Impact of prior bevacizumab therapy on the incidence of ramucirumab-induced proteinuria in colorectal cancer: a multi-institutional cohort study.

BACKGROUND: The association between prior bevacizumab (BEV) therapy and ramucirumab (RAM)-induced proteinuria is not known. We aimed to investigate this association in patients with metastatic colorectal cancer (mCRC). METHODS: mCRC patients who received folinic acid, fluorouracil, and irinotecan (FOLFIRI) plus RAM were divided into with and without prior BEV treatment groups. The cumulative incidence of grade 2-3 proteinuria and rate of RAM discontinuation within 6 months (6M) after RAM initiation were compared between the two groups. RESULTS: We evaluated 245 patients. In the Fine-Gray subdistribution hazard model including prior BEV, age, sex, comorbidities, eGFR, proteinuria ≥ 2 + at baseline, and later line of RAM, prior BEV treatment contributed to proteinuria onset (P < 0.01). A shorter interval between final BEV and initial RAM increased the proteinuria risk; the adjusted odds ratios (95% confidence intervals) for the intervals of < 28 days, 28-55 days, and > 55 days (referring to prior BEV absence) were 2.60 (1.23-5.51), 1.51 (1.01-2.27), and 1.04 (0.76-1.44), respectively. The rate of RAM discontinuation for ≤ 6M due to anti-VEGF toxicities was significantly higher in the prior BEV treatment group compared with that in the no prior BEV treatment group (18% vs. 6%, P = 0.02). Second-line RAM discontinuation for ≤ 6M without progression resulted in shorter overall survival of 132 patients with prior BEV treatment (P < 0.01). CONCLUSION: Sequential FOLFIRI plus RAM after BEV failure, especially within 55 days, may exacerbate proteinuria. Its escalated anti-VEGF toxicity may negatively impact the overall survival.

Effectiveness of administering zinc acetate hydrate to patients with inflammatory bowel disease and zinc deficiency: a retrospective observational two-center study.

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) patients frequently have zinc deficiency. IBD patients with zinc deficiency have higher risks of IBD-related hospitalization, complications, and requiring surgery. This study aimed to examine the effectiveness of zinc acetate hydrate (ZAH; Nobelzin) in IBD patients with zinc deficiency. METHODS: IBD patients with zinc deficiency who received ZAH from March 2017 to April 2020 were registered in this 2-center, retrospective, observational study. Changes in serum zinc levels and disease activity (Crohn's Disease Activity Index [CDAI]) before and after ZAH administration were analyzed. RESULTS: Fifty-one patients with Crohn's disease (CD, n = 40) or ulcerative colitis (UC, n = 11) were registered. Median serum zinc level and median CDAI scores significantly improved (55.5-91.0 µg/dL, P< 0.001; 171.5-129, P< 0.001, respectively) in CD patients 4 weeks after starting ZAH administration. Similarly, median serum zinc levels and CDAI scores significantly improved (57.0-81.0 µg/dL, P< 0.001; 177-148, P= 0.012, respectively) 20 weeks after starting ZAH administration. Similar investigations were conducted in groups where no treatment change, other than ZAH administration, was implemented; significant improvements were observed in both serum zinc level and CDAI scores. Median serum zinc levels in UC patients 4 weeks after starting ZAH administration significantly improved from 63.0 to 94.0 µg/dL (P= 0.002), but no significant changes in disease activity were observed. One patient experienced side effects of abdominal discomfort and nausea. CONCLUSIONS: ZAH administration is effective in improving zinc deficiency and may contribute to improving disease activity in IBD.