Case report: Proton pump inhibitor drug-related problem in pancreatic cancer patient unmasks pancreatic enzyme insufficiency.

INTRODUCTION: Palliative care aims to improve the quality of life of patients with a life-limiting or life-threatening illness and is multifaceted involving comprehensive interdisciplinary assessments and interventions. Interdisciplinary palliative care in the setting of untreatable cancer diagnoses is of particular importance due to additional considerations that must be taken as patients are often undergoing palliative chemotherapy and/or radiation therapy. These patients' complexity warrants special considerations and attentiveness to drug-related problems. CASE REPORT: The purpose of this case report is to highlight the importance of both complete and comprehensive medication histories in cancer care and the impact of proton pump inhibitors on pancreatic enzyme insufficiencies secondary to pancreatic cancers. This case involves a drug-related problem involving three medications that are commonly used in pancreatic cancer patients: pancreatic enzyme replacement therapy, a proton pump inhibitor, and a fluoroquinolone antibiotic. The patient presented in this case report is an 80-year-old man diagnosed with unresectable pancreatic cancer with a history of symptomatic gastroesophageal reflux disease managed with a proton pump inhibitor, specifically tablets of the 40 mg strength of pantoprazole magnesium taken orally once daily. During the patient's first of five 28-day cycles of palliative-intent chemotherapy with gemcitabine and nab-paclitaxel, the patient presented to the emergency department due to fever and, although not severely neutropenic, was prescribed amoxicillin/clavulanate and ciprofloxacin due to his advanced age. After reading a patient advisory on a ciprofloxacin patient information sheet that advised avoidance of concomitant administration of ciprofloxacin and magnesium, the patient self-discontinued his pantoprazole as it was a magnesium salt formulation. This discontinuation was followed by two weeks of persistent foul-smelling diarrhea, flatulence, and abdominal pain. MANAGEMENT AND OUTCOME: The patient's healthcare team symptomatically managed the patient with oral and intravenous rehydration unaware of the cause of the symptoms. A trial of pancreatic enzyme replacement therapy was initiated; however, it was unsuccessful in resolving his symptoms. After further investigation and a more in-depth patient interview, it was discovered that the discontinued proton pump inhibitor was likely the cause of the patient's new symptoms and was subsequently re-initiated. Pancreatic enzyme replacement therapy in combination with re-initiation of pantoprazole therapy essentially resolved all symptoms. DISCUSSION: Before his diagnosis of unresectable pancreatic cancer, the patient had been on proton pump inhibitor therapy for nearly a decade. He had significant atrophy of the pancreas and an undoubtedly decreased pancreatic enzyme and bicarbonate production; however, he did not experience foul-smelling diarrhea indicative of pancreatic enzyme insufficiency while he was on his proton pump inhibitor. We believe that with his proton pump inhibitor therapy, he was unknowingly being partially treated for his worsening pancreatic enzyme insufficiency, specifically the component related to his lack of bicarbonate production and secretion. His discontinuation of his proton pump inhibitor led to a decrease in gastric acid, small bowel, and normal intraduodenal pH, which resulted in any remaining pancreatic enzyme reserve to become non-functional, unmasking his pancreatic enzyme insufficiency. An initial empiric trial of pancreatic enzyme replacement therapy failed in the absence of a proton pump inhibitor; however, within days of restarting his proton pump inhibitor along with pancreatic enzyme replacement therapy, his gastrointestinal symptoms completely resolved. This is due to the decrease of gastric and intraduodenal acidity, which better enabled the function of pancreatic enzymes present in pancreatic enzyme replacement therapy.

Preventing drug vial wastage and reducing expenditure associated with injectable cancer drugs: International oncology pharmacy survey.

PURPOSE: Our objective was to determine what vial sharing techniques and other strategies were being used globally to reduce wastage from partially used single-use drug vials, what barriers are preventing these strategies being employed, and what savings are being achieved. METHODS: A survey, comprising 19 questions, was distributed to the membership of the International Society of Oncology Pharmacy Practitioners and British Oncology Pharmacy Association. Questions asked included how parenteral cancer drugs are obtained and prepared, what vial sharing strategies are used, what means are employed to extend stability, how prepared products are reused and what cost savings are achieved. RESULTS: In all, 74 responses were received from 20 countries, most from the United Kingdom. Some manufacturing is done by 60.8% of institution, with 41.9% making all products. Vial sharing strategies, for frequently used drugs, were employed in 53% of cases. Barriers preventing vial sharing being used included government legislation, USP 797 guidelines, and health insurance companies. Extension of stability was possible for 70.2% of centres. Most respondents reported reduction in cytotoxic and biological waste, and alleviation of drug shortages from vial sharing utilisation. Cost savings were achieved in 74% of cases and was significant in one third. CONCLUSIONS: The survey has determined that drug vial wastage and expenditure can be reduced, and vial sharing facilitates this. International collaboration plus the assistance of governments and the pharmaceutical industry is vital in achieving this aim. These findings can hopefully guide oncology pharmacy in establishing appropriate strategies to reduce wastage internationally.

Use of nab-paclitaxel and gemcitabine in pancreatic cancer without granulocyte colony-stimulating factor: A multicenter real-world experience.

INTRODUCTION: The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. METHODS: A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. RESULTS: Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1-7.4), and median overall survival of 11.1 months (95% CI, 9.5-12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8-6.5), and median overall survival of 19.3 months (95% CI, 12.6-26.0). CONCLUSIONS: The patient's progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

Education strategy for the implementation of oncology biosimilars essential for operational and patient safety in Alberta, Canada.

Medication errors involving look alike sound alike (LASA) medications have widely been recognized to contribute to patient harm. Oncology biosimilars are considered to be LASA medications and require additional measures for operational safety. The Cancer Care Alberta (CCA) Pharmacy Educators developed an education strategy to ensure operational and patient safety during the implementation phase for oncology biosimilars in Alberta, Canada. This resulted in a smooth adoption of oncology biosimilars. As future oncology biosimilars are introduced, this framework will serve as the foundation to educate and train oncology pharmacy staff.

Medication reconciliation in ambulatory oncology new patient clinics.

Medication Reconciliation (MedRec) is an essential part of safe medication management and plays a key role in ensuring patient safety. A variety of methods and a number of different healthcare disciplines can be involved in the MedRec process and the timing and location of conducting MedRec can vary. In an effort to streamline the process in ambulatory oncology new patient clinics, a pilot of an alternative approach was undertaken whereby pharmacists with advanced prescribing privileges completed MedRec with patients prior to their clinic visit. Evaluation of the pilot was completed through the collection of various metrics, a pharmacist focus group, healthcare staff and patient surveys. Overall the evaluation indicated that there are multiple factors to consider regarding the timing and method of MedRec completion. The various phases of the pilot demonstrated that flexibility to the process is key and ongoing efforts are required at reducing duplication.

International Society of Oncology Pharmacy Practitioners (ISOPP) position statement: Role of the oncology pharmacy team in cancer care.

The Oncology Pharmacy Team (OPT), consisting of specialty-trained pharmacists and/or pharmacy technicians, is an integral component of the multidisciplinary healthcare team (MHT) involved with all aspects of cancer patient care. The OPT fosters quality patient care, safety, and local regulatory compliance. The International Society of Oncology Pharmacy Practitioners (ISOPP) developed this position statement to provide guidance on five key areas: 1) oncology pharmacy practice as a pharmacy specialty; 2) contributions to patient care; 3) oncology pharmacy practice management; 4) education and training; and 5) contributions to oncology research and quality initiatives to involve the OPT. This position statement advocates that: 1) the OPT be fully incorporated into the MHT to optimize patient care; 2) educational and healthcare institutions develop programs to continually educate OPT members; and 3) regulatory authorities develop certification programs to recognize the unique contributions of the OPT in cancer patient care.

Centralized preparation of chemotherapy for remote administration.

Increasingly stringent pharmacy standards for preparation of sterile products necessitated a review of the feasibility of continuing to maintain chemotherapy sterile production facilities across the provincial cancer programme. The concept of centrally produced chemotherapy that could be shipped to various locations as a remote service delivery model was explored. Key planning principles were established and detailed processes were developed to test this change in service delivery at one small cancer centre. Following the successful implementation and evaluation of the remote service delivery model at one centre, the programme was rolled out to an additional four centres.

Implementation of an online chemotherapy checking training module enhances scope of practice and ensures competency.

Chemotherapy checking is a complex task and requires a high level of alertness and attention to detail. Learning tools are required to teach the fundamental principles of chemotherapy checking. In conjunction with a graphic design team and with input from Human Factors specialists, an online chemotherapy checking training module was created. A variety of learning methods were incorporated including pre-reading, hands on training, case scenarios, and exam questions. The necessary skills to safely complete chemotherapy checking can be enhanced by the use of this training module.

Baxter elastomeric pumps: Weighing as an alternative to visual inspection.

Purpose Elastomeric pumps are used to administer 46-hour infusions of 5-fluorouracil (5FU). Baxter suggests patients visually monitor their pumps to ensure that infusions are proceeding correctly. This can be confusing and lead to concerns about under- or over-dosing. Baxter has not considered weighing pumps as a validated method for monitoring. This study aims to validate weighing as a more accurate method for patients and healthcare professionals, and describe real life Baxter Infusor™ variability. Methods Patients who had been started on a 46-hour 5FU infusion returned to the clinic approximately 24 h after starting treatment. The pump was weighed on a StarFrit kitchen scale, and date, time, and weights recorded. Patients were asked if they had a preference for weighing or visually inspecting their pump. Results Pumps ( n = 103) were weighed between 17.25 and 27.5 h after connection. The average weight of a pump was 189 g. Of 103 pumps weighed, 99 weighed less than expected, corresponding to average flow rates of 5.69 mL/h over the elapsed time. The expected flow rate is 5 mL/h with 10% variability. Average flow rates within the 17.25- to 27.5-hour window were 4.561 mL/h, which is 8.78% slower than expected, but within the 10% known variability. Forty-seven percent of patients didn't have a preference for either method, but for those who did have a preference, more than twice as many preferred weighing. Conclusion With proper education, weighing Baxter Infusors at home with kitchen scales can be an accepted and objective alternative to the current recommendation of visual inspection.

Incidence of late onset neutropenia associated with rituximab use in B cell lymphoma patients undergoing autologous stem cell transplantation.

Reversible late onset neutropenia associated with rituximab has been reported with incidence rates varying from 15 to 70% in B cell lymphoma patients receiving autologous stem cell transplantation. We conducted a retrospective descriptive study at one tertiary care center in adult B cell lymphoma patients treated with rituximab and autologous stem cell transplantation between 1 January 2004 and 30 June 2014. Late onset neutropenia was defined as an absolute neutrophil count <1.0 × 109 cells/L after neutrophil engraftment and less than six months post autologous stem cell transplantation. The primary objective was to determine the incidence of late onset neutropenia. The secondary objectives were to examine whether the use of rituximab with re-induction therapy, mobilization or high dose chemotherapy regimens increased the risk for late onset neutropenia, and to evaluate infectious complications. Of 315 subjects, 92 (29.2%) developed late onset neutropenia. Mobilization regimens containing rituximab (OR 2.90 95% CI: 1.31-6.40), high dose chemotherapy containing rituximab (OR 1.87 95% CI: 1.14-3.05), and exposure to rituximab in either or both regimens (OR 3.05 95% CI: 1.36-6.88) significantly increased the risk of late onset neutropenia. While neutropenic, 17.4% experienced an infection, 7.6% experienced febrile neutropenia, and 5.4% were hospitalized. In conclusion, rituximab with mobilization or high dose chemotherapy may increase the risk of late onset neutropenia post autologous stem cell transplantation.

Opportunities to significantly reduce expenditure associated with cancer drugs.

AIM: To identify cancer drugs amenable to strategies for reducing expenditure and avoiding drug wastage. METHODS: Information was sourced from product information in 20 countries on parenteral cytotoxic agents, and cancer and noncancer monoclonal antibodies. Data were collected on vial sizes, overage, stability and presentation forms. RESULTS: Vial size availability varied significantly between countries, with often only single vial sizes for numerous medications. Overage was poorly reported. Stability data were inconsistent and variable between countries, with most drugs only having a 24 h expiry. Three cancer-indicated monoclonal antibodies, thought suitable for prefilled syringe administration, were only available as vials. CONCLUSION: Many expensive cancer drugs are suitable for global cost-reduction strategies. Collaboration is vital to affecting change and reducing expenditure.

Baxter elastomeric pumps: Feasibility of weight estimates.

Purpose Elastomeric pumps are used to infuse a 46-h fluorouracil protocol and patients are asked to visually inspect the pump daily. The pump has a variability of ±10% and there are additional patient variables that can increase this. The feasibility of weighing the pump rather than a visual inspection along with the secondary objective to confirm the pump's variability in real world conditions was undertaken. Methods Empty pumps were weighed using both pharmacy and kitchen scales. Pumps upon completion of the 46-h infusion were also weighed using both pharmacy and kitchen scales. Results The kitchen scale was as accurate as the pharmacy grade scale. Disconnected pumps showed the expected variability from using these infusor pumps along with a few showing greater variability likely due to patient variables. Conclusion Weighing pumps appears to be feasible both at the pharmacy and home level. Next steps would be to weigh pumps during the infusion to validate an alternate method to simple visual inspection for patients to confirm proper infusing of the pump at their home.

Worksheets with embedded checklists support IV chemotherapy safer practice.

Following a review of a chemotherapy medication adverse event where the incorrect medication was prepared by a pharmacy, a number of steps were taken to review the literature and best practice information related to checking processes for the preparation of parenteral chemotherapy. Concepts such as identification of critical stop check points, independent double checks, and human factors principles were reviewed and incorporated into newly designed chemotherapy preparation worksheets with embedded checklists. Usability testing and staff feedback during implementation revealed a number of key learning points that resulted in additional work to further improve the chemotherapy worksheets with embedded checklists and highlighted the need for a culture of continuous quality improvement.

Effects of gender on capecitabine toxicity in colorectal cancer.

BACKGROUND: Capecitabine is a highly water soluble prodrug of 5-fluorouracil that is dosed by patient body surface area. Body surface area dosing makes no allowances for differences in body composition. There is mounting evidence that lean body mass is a better predictor of toxicity than body surface area for drugs which distribute into the lean compartment. Because women, on average, have lower lean body mass than men, we expect that women would experience a higher incidence of toxicity than men when body surface area dosing is used. OBJECTIVE: To determine whether female colorectal cancer patients experienced a higher incidence of dose-limiting toxicity than men when treated with adjuvant capecitabine. METHODS: We conducted a retrospective chart review of colorectal cancer patients treated with adjuvant capecitabine at our institute between 2008 and 2012. Patients receiving capecitabine were identified from the pharmacy dispensing database and then screened for inclusion. Dosing and toxicity information were gathered and dose-limiting toxicity incidence (defined as a composite endpoint of dose delay, dose reduction, or discontinuation of therapy) was compared between males and females using the chi-square test. Binary logistic regression analysis was then performed to account for differences between male and female populations. RESULTS: A total of 299 patients (163 males, 136 females) met inclusion criteria. Females had a significantly higher dose-limiting toxicity incidence than males (67.7 vs. 52.2%, p = 0.007). Relationships between gender and dose-limiting toxicity incidence remained significant after logistic regression analysis (OR: 2.04; 95% CI: 1.23-3.36). CONCLUSION: Female colorectal cancer patients experience a higher dose-limiting toxicity incidence than male patients when given adjuvant capecitabine dosed according to body surface area.

Medication safety and the administration of intravenous vincristine: international survey of oncology pharmacists.

PURPOSE: The risk of medication errors with vincristine administration is well documented. Our objective was to ascertain how vincristine is administered worldwide and determine what strategies for preventing the accidental intrathecal administration of vincristine are in place. METHODS: A survey, comprising 28 questions, was distributed to 363 International Society of Oncology Pharmacy Practitioners members from 42 countries via email. Questions were asked on methods of vincristine administration, intrathecal drug administration and strategies used to prevent medication errors. A reminder was sent and the survey was available on the International Society of Oncology Pharmacy Practitioners website. Only one survey per institution was requested. RESULTS: In all, 62 responses from 15 countries were received, with the majority from Australia. Vincristine was dispensed in mini-bags in 77.4% of centres, though some also used syringes. Syringes were used in 31.1% of centres, with half these doses prepared undiluted. Administration took 5 to 15 minutes in most centres (78.8%). The most common reasons for still using syringes were perceived risk of extravasation and faster infusion time. Despite numerous vincristine administrations, extravasation was very rare. Other recommended strategies for error prevention were in use in the majority of centres. CONCLUSION: Comparisons with three previous surveys are difficult as the majority of respondents in those studies were from the USA. A number of areas appear to have improved, particularly the preparation of vincristine in mini-bags, but they are far from perfect. Deaths continue to occur following accidental intrathecal administration of vincristine. International Society of Oncology Pharmacy Practitioner members are urged to lead the way in incorporating strategies for prevention into institutions worldwide.

Feasibility of using the Multinational Association of Supportive Care in Cancer Antiemesis Tool for assessment of chemotherapy-induced nausea and vomiting at the Tom Baker Cancer Centre.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) has been shown to adversely impact patient anxiety, quality of life, treatment adherence, and use of health care resources. CINV control still remains a challenge, and lack of effective communication between the patient and clinician has been highlighted in the literature as the main barrier to optimal control. The Multinational Association of Supportive Care in Cancer (MASCC) has developed a tool (MASCC Antiemesis Tool (MAT)) to improve assessment and subsequent management of CINV by enhancing communication between patients and their clinicians. This study assessed the feasibility of using the MAT in patients at the Tom Baker Cancer Centre. The secondary objective was to describe the incidence of CINV as identified by the tool. METHODS AND MATERIALS: This study involved a prospective survey using the MAT in patients receiving intravenous chemotherapy. Subjects completed the MAT twice post-chemotherapy regarding CINV symptoms and returned it at their next clinic appointment. Participants were also surveyed to evaluate feasibility with regard to using the MAT. RESULTS: Of the 50 patients recruited, 56% returned surveys. The majority of patients reported that the MAT facilitated communication with their clinician, particularly those who had experienced CINV. Fifty-four percent of patients who returned the MAT reported CINV; however, less than half of them had received American Society of Clinical Oncology-recommended antiemetic regimens. Only four patients with CINV had antiemetic changes made for subsequent cycles. CONCLUSION: The MAT is a feasible tool which can improve communication of CINV symptoms between patients and clinicians, a foundational step toward improving CINV management.

Medication adherence among adults prescribed imatinib, dasatinib, or nilotinib for the treatment of chronic myeloid leukemia.

BACKGROUND: Oral tyrosine kinase inhibitors are the standard of care for chronic myeloid leukemia. Tyrosine kinase inhibitors are administered in an outpatient setting for an indefinite period which may negatively impact adherence. Non-adherence to tyrosine kinase inhibitors is associated with disease progression. OBJECTIVES: To evaluate the need for adherence-enhancing interventions, this study was designed to determine the proportion of chronic myeloid leukemia patients non-adherent to their tyrosine kinase inhibitor regimen. The secondary objective was to identify the influence of patient characteristics on tyrosine kinase inhibitor adherence. METHODS: Cross-sectional retrospective chart and dispensing record reviews were performed to identify patients receiving a tyrosine kinase inhibitor from 1 June 2010 to 31 January 2012. Adherence was evaluated using the medication possession ratio. RESULTS: A total of 124 patients were included. Thirty-eight (31%) patients were non-adherent to their tyrosine kinase inhibitor regimen. Patients not receiving concurrent medications were more likely to be non-adherent (odds ratio (OR) 2.33, 95% confidence interval (CI) 1.05-5.13, p=0.04). The median medication possession ratio was 0.95 (IQR=0.83-1.07). Median medication possession ratio was lower in patients receiving imatinib compared to dasatinib or nilotinib (0.95 vs. 1.00, p=0.01) and in those less than 50 years old compared to those greater than 50 years old (0.92 vs. 0.97, p=0.02). CONCLUSIONS: Optimal tyrosine kinase inhibitor adherence in chronic myeloid leukemia patients poses a significant obstacle in achieving best possible outcomes while reducing healthcare costs. In this study, one in three chronic myeloid leukemia patients treated with a tyrosine kinase inhibitor were non-adherent to their regimen. Those at higher risk of non-adherence were on no concurrent medications, less than 50 years old, and those treated with imatinib. Active intervention to improve tyrosine kinase inhibitor adherence should be developed, implemented, and evaluated to improve patient outcomes at our center.

Does gastric acid suppression affect sunitinib efficacy in patients with advanced or metastatic renal cell cancer?

INTRODUCTION: Renal cell cancer is a chemotherapy-insensitive cancer treated by vascular endothelial growth factor receptor antagonists. Recently, a question has arisen on whether there is an interaction between tyrosine kinase inhibitors, such as sunitinib, and acid suppressing agents. METHODS: A retrospective chart review was conducted for patients at two tertiary care centers who received sunitinib between 1 January 2006 and 31 March 2013. Using electronic systems and a province-wide electronic health records database, medication dispensing records were obtained. A univariate Cox's proportional hazard model determined if acid suppression had effects on progression-free survival and overall survival. RESULTS: Of 383 patient charts reviewed, 231 were included in the study. Patients on intermittent acid suppression, lost to follow-up or received sunitinib for less than one week were excluded from the study. The median age of the study population was 65. Patients who received no acid suppression (n = 186) had a median progression-free survival of 23.6 weeks (95% CI, 19.0-31.9 weeks) and patients who received continuous acid suppression (n = 45) had a median progression-free survival of 18.9 weeks (95% CI, 11.0-23.7 p = 0.04). A median overall survival of 62.4 weeks (95% CI, 42.0-82.7 weeks) was observed in the group with no acid suppression, while a median overall survival of 40.9 weeks (95% CI, 26.1-74.4 weeks) was observed in the continuous acid suppression group (p = 0.02). CONCLUSION: There was a significant difference in progression-free survival and overall survival between the acid suppressed and no acid suppression groups. Further research is required to confirm this potential interaction.