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.

Fentanyl titration for cancer pain: continuous subcutaneous injection and a once-daily transdermal patch - case series.

OBJECTIVES: Continuous subcutaneous injection (CSCI) followed by a once-daily transdermal patch is a reasonable strategy for rapid titration of fentanyl in patients with cancer pain who are unable to take oral medication or have renal impairment, but the effectiveness and safety have not been demonstrated. METHODS: Medical records of patients with moderate to severe cancer pain who underwent titration of fentanyl by CSCI between October 2019 and October 2021 at Kitano Hospital, Osaka, Japan, were retrospectively reviewed. The dose of fentanyl was increased to a maximum of 0.05 mg/hour. If the dose was inadequate, the fentanyl patch was added on CSCI. When pain relief was adequate, CSCI was completely converted to the patch. RESULTS: Thirty-three patients were enrolled. Titration was completed successfully in 28 patients (85%) over a median of 2 days. The average Numeric Rating Scale for pain decreased by at least 66% in 22 patients (67%) and by at least 33% in 7 (21%). After conversion to the patch, two patients (6.1%) required to increase the dose of fentanyl within a week. Two patients (6.1%) experienced moderate drowsiness during titration. CONCLUSIONS: Fentanyl titration by CSCI is an effective and safe method for achieving rapid pain control.

[A case of lung metastases of carcinoma of the ampulla of vater effectively treated with S-1].

A 70-year-old female patient underwent pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater in March 2007. In April 2009, multiple lung metastases were detected by CT scanning. The patient was treated with S-1 (80mg/day, day 1-28, followed by 2-weeks withdrawal)from April 2009. The shrinkage of lung metastases was diagnosed as a complete response based on the Response Evaluation Criteria in Solid Tumors(RECIST). No severe toxicities were observed. S-1 is an effective and safe anti-cancer agent available for lung metastases of carcinoma of the ampulla of Vater.