Utilization and toxicity patterns of 2-weekly (Q2W) versus 4-weekly (Q4W) nivolumab for treatment of adjuvant and metastatic melanoma at BC cancer.

BACKGROUND: Nivolumab, an immune checkpoint inhibitor used to treat several malignancies, is associated with immune-related adverse events (IrAEs). Original dosing for melanoma was 3 mg/kg (maximum 240 mg) every 2 weeks (Q2W). Based on simulation studies depicting similar efficacy and toxicity to original dosing, extended interval dosing of 6 mg/kg (maximum 480 mg) every 4 weeks (Q4W) was introduced. OBJECTIVE: This study will compare safety between Q2W and Q4W dosing at BC Cancer in melanoma patients. METHODS: Retrospective chart review for reported incidence, onset, and severity of IrAEs in melanoma patients treated with nivolumab Q2W and Q4W dosing was completed. Fisher's test was conducted for first incidence IrAEs using Microsoft Excel. RESULTS: Seventy-one patients were identified (Q2W n = 35, Q4W n = 36). Baseline characteristics were similar in both groups. No statistically significant difference was found in incidence of IrAEs between Q2W and Q4W dosing (Q2W 40% vs Q4W 50%, p = 0.477). Rash was most common (Q2W 79% vs Q4W 50%) followed by hypothyroidism (Q2W 33% vs Q4W 20%). Median onset of IrAEs seemed later with Q4W dosing (Q2W cycle 1 vs Q4W cycle 4). Regardless of dosing, most IrAEs were grade 1-2 in severity (Q2W 100% vs Q4W 89%). CONCLUSION: Q4W dosing is associated with comparable incidence and potentially later onset of IrAEs compared to Q2W dosing. Most IrAEs in both dosing groups were similar and mild. Therefore, Q4W dosing offers a safe alternative to Q2W dosing while providing benefits including decreased workload for staff, decreased clinic visits, and viral exposure by patients.

Survival outcomes associated with different sunitinib dosing regimens in metastatic renal cell carcinoma.

BACKGROUND: Standard dosing regimen of sunitinib for metastatic renal cell carcinoma consists of four weeks treatment followed by two weeks rest (intermittent dosing). Alternative regimens have been suggested, including continuous daily dosing (continuous dosing) and non-conventional dosing (non-conventional dosing: e.g. two weeks on/one week off, non-conventional dosing), to provide more individualized therapy with less toxicities. It is unclear whether non-standard sunitinib dosing affects survival outcomes. PATIENTS: Metastatic renal cell carcinoma patients treated with sunitinib between 1 July 2007 and 1 July 2011 at our institution. METHODS: Medical records and dispensing data were reviewed retrospectively to categorize sunitinib dosing as intermittent dosing, continuous dosing, or non-conventional dosing. Primary outcome was to compare overall survival associated with varying regimens, with secondary outcomes of progression-free survival and incidence of treatment discontinuation due to adverse effects. RESULTS: A total of 180 patients were identified. Most patients received intermittent dosing (n = 120, 67%), followed by continuous dosing (n = 32, 18%) and non-conventional dosing (n = 28, 16%). Compared to intermittent dosing, continuous dosing was associated with similar overall survival (median 9 vs. 13 months, HR 0.67, 95% CI: 0.43-1.06, p = 0.088) while non-conventional dosing was associated with significantly longer overall survival (median 9 vs. 23 months, HR 0.55, 95% CI: 0.34-0.90, p = 0.016). Progression-free survival was significantly better for continuous dosing (median 4 vs. 9 months, HR 0.61, 95% CI: 0.40-0.94, p = 0.025) and non-conventional dosing (median 4 vs. 10 months, HR 0.61, 95% CI: 0.39-0.95, p = 0.03) when compared to intermittent dosing. Similar to prior sunitinib trials, a significant proportion of patients (20%) discontinued sunitinib therapy due to adverse effects. CONCLUSIONS: Based on retrospective, real-world data, alternative sunitinib dosing regimens appear to be viable options for patients with metastatic renal cell carcinoma.

Approach to initiating QT-prolonging oncology drugs in the ambulatory setting.

Since the introduction of regulatory drug approval guidance on the evaluation of QT interval prolongation, an increasing number of drug monographs has included cautions on the risk of QT prolongation. For example, QT prolongation is mentioned in the Canadian product monographs of 29 drugs commonly seen in oncology practice. This presents two major challenges. First, most guidelines and risk predictive tools for QT prolongation have been developed for hospitalized patients in acute care settings. In contrast, most QT-prolonging oncology drugs are used in medically stable patients in the ambulatory setting. Second, many oncology drugs are unique for their indications and non-QT prolonging alternative agents are often not available. In this review, we will outline an empiric initial approach to ambulatory cancer patients who are treated with oncology drugs which may prolong QT interval. This includes the predictive value of QT prolongation on torsades de pointes, the risk factors of the patients and the drugs, and the limitations of existing guidance in this area.

Development of a systematic approach to pharmaceutical industry's patient assistance programs on accessing unfunded cancer drugs.

Background New oncology drugs usually become commercially available several months before the funding decisions are made by provincial public payers. Increasingly, patient assistance programs are being set up by pharmaceutical companies in order to facilitate access of their new cancer drugs before public funding decisions are finalized. We discovered that there is a need to keep this information up to date and available in a central repository, thus we have created a centralized patient assistance chart for use by all who require information on accessing unfunded drugs in our province. Methodology The project was carried out at a publicly funded provincial cancer care organization that oversees parenteral and oral chemotherapy treatments across our province. The drug information pharmacist at this organization developed a method of scoping information on upcoming therapies by reviewing a series of recommendations made by various organizations that review oncology treatments. A standard process was developed for including information on the patient assistance chart that is available on the organizations website. Results As of May 2016, the repository contains information on 47 patient assistance programs involving 24 unfunded antineoplastic drugs for various indications. This compared to (7) when it was maintained by a single centre in 2004 and 10 when the process was first centralized in 2009. Conclusion The benefit of patient assistance program availability allows patients to access medications when provincial funding is not available. A standardized approach and methodology to evaluating information was established by our drug information pharmacist; thus allowing for a consistent approach to dissemination of information on assessing unfunded cancer drugs in our province.

Safe handling of monoclonal antibodies: Too large to be hazardous?

It has been argued that the larger molecular weight of hazardous monoclonal antibodies may prevent their dermal absorption via occupational exposure. However, this assertion does not seem to be supported by direct evidence. Although the larger molecular weight may render monoclonal antibodies less probable to achieve therapeutic systemic level through dermal absorption, the concern in occupational health is whether these drugs can possibly attain a detectable level through repeated dermal exposure. Currently, there is no direct evidence to support a particular molecular weight above which a drug cannot achieve a detectable level following repeated occupational exposure. Therefore, the precautionary principle would dictate that repeated exposure of healthcare workers to hazardous monoclonal antibodies should be kept to a minimum.

Loperamide and cardiac events: Is high-dose use still safe for chemotherapy-induced diarrhea?

High-dose loperamide is often used for the acute management of chemotherapy-induced diarrhea, with a maximum daily dosing of up to 24 mg. Recently, the US Food and Drug Administration has issued a warning that loperamide can cause rare serious cardiac events, including QT prolongation, torsades de pointes, cardiac arrest and death. Most events were reported in patients taking very high doses for an extended period of time. Daily intake ranged from 64 mg to 1600 mg, often continuously for weeks or months. In addition, the reported serum levels of loperamide ranged from 22 ng/mL to 210 ng/mL, which is likely significantly higher than that expected from patients taking the recommended doses for chemotherapy-induced diarrhea. Overall, the incidence of serious cardiac events associated with loperamide remains low. In balance, the risk of uncontrolled complications from chemotherapy-induced diarrhea is likely greater than the rare cardiac risk associated with the chronic misuse of much higher doses of loperamide.