Journal of Oncology Pharmacy Practice

Carboplatin-based chemotherapy offers high response rates and improved overall survival for women with epithelial ovarian cancer, but its use is limited by the occurrence of hypersensitivity reactions. To evaluate the efficacy of prophylactic diphenhydramine for hypersensitivity reaction prevention, we reviewed the incidence of hypersensitivity reactions and identified patients at high risk of hypersensitivity reactions.

Women receiving ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer were identified from our institutional database at the Princess Margaret Cancer Centre. Institutional policy was changed in 2009 to introduce diphenhydramine prophylaxis for patients receiving ≥6 cycles of carboplatin. Additional clinical data were abstracted from the patient record.

Between 2006 and 2012, 450 women received ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer. Two hundred and ninety-one women received prophylaxis with diphenhydramine. Carboplatin-induced hypersensitivity reactions occurred in 41 of 449 patients (9%). Univariable predictors of carboplatin-induced hypersensitivity reactions included administration of 8 to 10 cycles of carboplatin, history of other drug allergies and a platinum-free interval >12 months. BRCA mutational status was not predictive. In a multivariable analysis, the number of cycles of carboplatin and a platinum-free interval >12 months were independent predictors of hypersensitivity reactions. There was a trend towards diphenhydramine prophylaxis reducing the incidence of hypersensitivity reactions in women with a platinum-free interval compared to continuous delivery; this was most marked when the platinum-free interval was >12 months (n = 64) (OR: 0.2 (95% CI: 0.046–0.83), p = 0.03).

The administration of diphenhydramine to women who have a platinum-free interval may reduce the risk of hypersensitivity reaction, but prospective evaluation is required.

This study was conducted to determine whether there is contamination on exterior drug packaging using shipping totes from the distributor and carousel storage bins as surrogate markers of external packaging contamination.

A two-part study was conducted to measure the presence of 5-fluorouracil, ifosfamide, cyclophosphamide, docetaxel and paclitaxel using surrogate markers for external drug packaging. In Part I, 10 drug distributor shipping totes designated for transport of hazardous drugs provided a snapshot view of contamination from regular use and transit in and out of the pharmacy. An additional two totes designated for transport of non-hazardous drugs served as controls. In Part II, old carousel storage bins (i.e. those in use pre-study) were wiped for snapshot view of hazardous drug contamination on storage bins. New carousel storage bins were then put into use for storage of the five tested drugs and used for routine storage and inventory maintenance activities. Carousel bins were wiped at time intervals 0, 8, 16 and 52 weeks to measure surface contamination.

Two of the 10 hazardous shipping totes were contaminated. Three of the five-old carousel bins were contaminated with cyclophosphamide. One of the old carousel bins was also contaminated with ifosfamide. There were no detectable levels of hazardous drugs on any of the new storage bins at time 0, 8 or 16 weeks. However, at the Week 52, there was a detectable level of 5-FU present in the 5-FU carousel bin.

Contamination of the surrogate markers suggests that external packaging for hazardous drugs is contaminated, either during the manufacturing process or during routine chain of custody activities. These results demonstrate that occupational exposure may occur due to contamination from shipping totes and storage bins, and that handling practices including use of personal protective equipment is warranted.

Appropriate use of oral chemotherapy is a challenge for patients and clinicians. The purpose of this study was to analyze cancer patients’ use of oral chemotherapies and identify opportunities to improve adherence.

We developed a 30-question survey to address frequency and reasons for reducing/skipping doses; sources of information for oral chemotherapy use; perceived importance of food–drug effects; and ease of understanding labeling directions.

Ninety-three patients taking oral chemotherapies with chronic myeloid leukemia, renal cell carcinoma, breast cancer, and colorectal cancer completed the survey. This was a well-educated population with 69% (n = 62) having completed some college; 51% (n = 47) female and 59% (n = 54) older than 50 years of age. Thirty percent of patients reported forgetting to take their oral chemotherapy at least “sometimes”. Younger patients (<50 vs. ≥50, p = 0.002), shorter treatment duration (<6 vs. ≥6 months p = 0.03), or with chronic myeloid leukemia (vs. other diagnoses, p = 0.015) forget to take their oral chemotherapy at higher rates. Twenty-three percent (n = 21) indicated they intentionally skipped their oral chemotherapies and 38% (n = 8) of those did not inform their physicians. Forty-one percent (n = 28) taking drugs with significant food–drug effects did not think about their last meal before taking their oral chemotherapy and 80% (n = 55) did not understand the potential interactions. Additionally, 39% (n = 36/92) never looked at labeling and 15% (n = 14/91) had difficulty understanding label directions.

There are three main barriers associated with appropriate use of oral chemotherapies: misunderstanding about the timing of drug with food; stopping drug without informing physicians; and difficulty understanding labeling directions. A multipronged approach is needed to optimize communication of directions for optimal oral chemotherapy use.

Tyrosine kinase inhibitors are increasingly used in the treatment of cancer. Drug interactions involving tyrosine kinase inhibitors are commonly encountered in clinical practice. The objective of this study was to describe the frequency of tyrosine kinase inhibitor-associated drug interactions among a cohort of oncology patients.

Adult patients were included who presented to either of two outpatient oncology practices and were prescribed a tyrosine kinase inhibitor during 2 January 2013 to 1 January 2015. Demographic and medication data were abstracted from electronic medical records. Lexicomp®, Micromedex Solutions®, and medication labeling were utilized to identify potential interactions between tyrosine kinase inhibitors and concomitant medications. Interactions were then assessed by the investigators for clinical significance. The primary outcome was the frequency of significant drug interactions involving tyrosine kinase inhibitors and concomitant medications. Secondary outcomes included describing the nature and clinical impact of interactions, and describing interactions by medication class.

A total of 356 patients were identified for analysis, in whom 244 potential interactions were identified, and 109 (44.7%) of which were considered severe. Decreased tyrosine kinase inhibitor absorption due to acid suppressive therapy and CYP3A4 interactions were the most frequent mechanisms of potential subtherapeutic and supratherapeutic concentrations, respectively. Potential clinical consequences included QTc prolongation (n = 53, 48.6%), decreased tyrosine kinase inhibitor concentration (n = 53, 48.6%), and increased tyrosine kinase inhibitor concentration (n = 3, 2.8%).

Safer alternative therapy and/or more frequent clinical monitoring should be considered if an interaction poses a significant risk of increased tyrosine kinase inhibitor toxicity or decreased tyrosine kinase inhibitor efficacy. Oncology pharmacists can play a role in screening for tyrosine kinase inhibitor-associated interactions, recommending alternative therapies or dosing strategies, and monitoring tyrosine kinase inhibitor efficacy and toxicity.

Increasing new cancer cases and approval of effective but expensive new drugs extending survival have led to unsustainable cancer care costs. Potential cost savings by a hypothetical dose down-rounding project of monoclonal antibodies at a community-based cancer center is presented.

From October 2014 through October 2015, metastatic cancer patients receiving monoclonal antibodies at CHI-Health St Francis Cancer Treatment Center in Grand Island, Nebraska, were identified through electronic health records. A total of 11 different types of monoclonal antibodies that were administered during the study period were identified. Trastuzumab, ofatumumab, and obinutuzumab did not require dose-rounding; thus, they were excluded from the analyses. Available vial size(s) and costs per milligram per average wholesale price for each monoclonal antibody were recorded. Costs of actual amounts prescribed were compared to the costs of theoretically reduced ≤5% and ≤10% doses rounded to the nearest vial sizes. Reduced doses resulting in a decreased number of opened vials qualified for meaningful dose down-rounding and were included in the analysis. Average actual dose reduction percentage resulting in cost savings for both groups was also calculated.

A total of 728 doses of eight monoclonal antibodies suitable for dose down-rounding were identified. Vial sizes of pembrolizumab and ipilimumab did not allow for a meaningful dose down-rounding. At the ≤5% dose down-rounding, 255 of 728 doses (35%) qualified with a potential annual cost savings of $220,793.80. At the ≤10% dose down-rounding, 526 of 728 doses (72%) qualified with a potential annual cost savings of $454,461.00. The average actual dose reduction was 2.4% for the ≤5% dose reduction group and 4.9% for the ≤10% dose reduction group. Overall average cost savings per qualifying dose reduction was around $865.00. More doses qualified for cost savings in the ≤10% dose reduction group. Significant differences between different monoclonal antibodies for dose rounding at either ≤5% (p = 0.002) or ≤10% (p < 0.001) were observed.

A practical dose down-rounding procedure may allow significant cost reduction in metastatic cancer setting, where the cure is not the goal. Drug waste can be avoided by convenient vial sizes or can even be eliminated by lyophilized forms like in trastuzumab. Our data reflect the monoclonal antibody use and potential cost savings with the proposed dose down-rounding approach in a community-based cancer program.

Pembrolizumab, a monoclonal antibody which inhibits the programmed cell death 1 receptor, has been shown to efficaciously enhance pre-existing immune responses to malignancies. However, safety concerns must also be considered as pembrolizumab use has been associated with several life-threatening immune-related adverse events (irAEs). We report a fatal case of pembrolizumab-induced myasthenia gravis in a patient with no prior myasthenia gravis history.

A 63-year-old male presented with right eyelid drooping, puffiness, blurred vision, and shortness of breath two weeks after an initial infusion of pembrolizumab. He was subsequently diagnosed with new onset acetylcholine-receptor positive myasthenia gravis. Despite aggressive treatment with corticosteroids, pyridostigmine, intravenous immunoglobulin, and plasmapheresis, the patient clinically deteriorated and ultimately expired from acute respiratory failure after a 12-day hospitalization.

Current package labeling for pembrolizumab warns against various irAEs associated with its use including pneumonitis, colitis, and endocrinopathies. To date, only one case of new onset myasthenia gravis and two case reports of myasthenia gravis exacerbation have been identified. This case further highlights the mortality risk associated with development of irAEs.

While rare, evidence for the development of MG associated with pembrolizumab is growing. Prompt recognition of symptoms and discontinuation of pembrolizumab is necessary to help improve prognosis.