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.

Safety Evaluation of Initial CT-P6 Administration for 30 min during the Switch from Reference Trastuzumab in Maintenance Infusion: A Multicenter Observational Study.

CT-P6 is a biosimilar of trastuzumab and is recommended to be administered for 30-90 min in subsequent maintenance infusions to prevent infusion-related reactions (IRRs). We administered CT-P6 for 30 min as the first injection and as an alternative to reference trastuzumab in the maintenance infusion and evaluated the safety of the administration. A total of 140 patients with breast or gastric cancer, who received a switch from tri-weekly reference trastuzumab to CT-P6 for 30 min in maintenance infusions, were retrospectively evaluated. Premedication was administered prior to an infusion of CT-P6 and a cytotoxic agent. However, premedication was not provided when CT-P6 was co-administered with pertuzumab or administered alone. The primary endpoint was the incidence of IRRs. The secondary endpoint was the incidence of diarrhea and skin toxicity. Ninety-five percent of the patients had breast cancer, and 44.3% had advance-stage cancer. The treatment included CT-P6 alone (17.9%) or with cytotoxic agents (23.6%), antihormonal drugs (25.7%), and pertuzumab (62.9%). Median administration time of trastuzumab at the switch was 13 administrations (range 2-140). Premedication was administered to 20.7% patients. One patient (0.7%) experienced grade 3 IRR. The frequency of diarrhea in the reference trastuzumab group and the CT-P6 group was 7.1 and 6.4%, respectively, and that of skin toxicity was 6.4 and 5.0%, respectively, without differences. In conclusion, we first demonstrated that an initial CT-P6 administration for 30 min during the switch from reference trastuzumab in maintenance infusion is an acceptable administration method.

[The Usefulness of a Pamphlet for Preventing Exposure to Antineoplastic Agents at Cancer Patients' Homes and an Awareness Survey for Pharmacists about Providing Information to Cancer Patients about Exposure to Antineoplastic Agents].

As the number of patients undergoing outpatient chemotherapy has increased, there is concern that cancer patients' family members are unknowingly exposed to antineoplastic agents at home through cancer patients' excrement or other secreted materials. In this study, we created a pamphlet that introduces several methods to prevent exposure to antineoplastic agents at home and conducted a questionnaire survey to assess the usefulness of the pamphlet. The results indicated that more than 90% of patients believed that the pamphlet was "useful" or "very useful" for ensuring safety with respect to antineoplastic agents at home. Further, most patients responded that the pamphlet decreased their anxieties about their disease and/or treatment. In order to examine pharmacists' involvement in providing information to cancer patients about exposure to antineoplastic agents, we conducted another questionnaire survey, with pharmacists working at Sapporo-Higashi Tokushukai Hospital and Sapporo Tokushukai Hospital. The results indicated that 41 out of 46 pharmacists practiced medication counseling; however, 39 pharmacists did not provide patients with instructions on ways to prevent exposure to antineoplastic agents at home. Their primary reason was a lack of adequate information to do so. Accordingly, the pamphlet prepared in our study would be an effective way to provide guidance for preventing exposure to antineoplastic agents at home.

[Prediction of gemcitabine treatment discontinuation based on platelet count before first administration].

Decrease in white blood cell (WBC), neutrophil or platelet (PLT) count due to treatment with gemcitabine (GEM) is a dose-limited factor (DLF). Even for cases that satisfy the standard criteria for initiation of GEM therapy, the scheduled therapy is reportedly occasionally discontinued because of decreased PLT or WBC count. Here, a retrospective study was made to predict the factor causing discontinuation of GEM treatment before its first administration. The results showed that PLT count immediately before the first administration was significantly less in the unfinished administration group than in the finished group. It was also demonstrated that a PLT count less than 16×10/4 mL before the first administration of GEM was the significant risk factor leading to discontinuation of GEM treatment. Thus, it was suggested that this result would be available as the dose reduction standard to determine the first dose of GEM treatment.