Pain descriptors of taxane acute pain syndrome (TAPS) in breast cancer patients-a prospective clinical study.

BACKGROUND: Taxane acute pain syndrome (TAPS) is a clinically significant side-effect of taxane chemotherapy, often described as arthralgia and myalgia that occurs 2-3 days after infusion. The aim of this study was to assess pain descriptors used by patients during their experience of TAPS. METHODS: A clinical prospective cohort study was conducted on breast cancer patients who had not received prior chemotherapy and were asked to complete diaries on three consecutive docetaxel treatment cycles on days 1-7, 14, and 21 (acute phase). Questionnaires to assess pain severity, descriptors of pain, and the interference in activities due to pain were adapted from the Brief Pain Inventory and the McGill Pain Questionnaire. Telephone questionnaire follow-up was done at 1, 3, 6, 9, and 12 months following docetaxel (delayed phase). RESULTS: The most commonly used descriptor for acute and chronic pain was "aching" (90-96%). However, in the delayed phase of the study, "burning" (32-50%), "radiating" (39-48%), and "sharp" (40-69%) were used more often. In both acute and chronic pain phases, most patients experienced moderate/severe pain regardless of the location. Pain in cycle 1 was predictive of pain in subsequent taxane cycles (p < 0.0001). Pain in cycle 3 was predictive of chronic pain (p < 0.002). CONCLUSIONS: The descriptors used by patients experiencing chemotherapy-induced pain (ChIP) may be reflective of the underlying mechanisms. It is suspected that TAPS initiates as an acute inflammatory pain, which over time develops into neuropathic pain, known as chemotherapy-induced peripheral neuropathy (CIPN). However, the subjective pain experience varies from patient to patient.

A prospective study of docetaxel-associated pain syndrome.

PURPOSE: To investigate the natural history of taxane-associated acute pain syndrome (TAPS) in a docetaxel patient cohort and to examine the long-term manifestation of TAPS. PATIENTS AND METHODS: For three consecutive treatment cycles, taxane-naive breast cancer patients completed diaries on days 1-7, 14, and 21 and telephone questionnaires 1, 3, 6, 9, and 12 months following treatment. Questionnaires to assess pain and interference were adapted from the Brief Pain Inventory. To examine the experience of arthralgia and myalgia as one syndrome, information on patient experiences with arthralgia or myalgia was elicited separately in order to determine how closely experiences of each toxicity correlated with each other. A ≥2 point increase from baseline was defined as an arthralgia or myalgia "pain flare," and only those with "flare" were included in calculations of incidence. RESULTS: A total of 278 patients were accrued. Thirty-eight patients were omitted due to missing information, and 24 patients were omitted due to metastatic disease, for a total of 216 patients overall and 188 in the docetaxel cohort. A total of 74.5% of docetaxel patients experienced joint pain flare, and 78.2% experienced muscle pain flare at some point in the overall course of three treatment cycles. Joint and muscle pain peaked on days 4-5 for each cycle, and median pain severity for both joint and muscle pain was 4/10 during the 21-day period. Median onset of joint pain flare was 3 days for cycle 1 and 4 days for cycles 2 and 3, with an average median duration of 4 days. Median onset of muscle pain flare was 4 days for all three cycles, with a median duration of 4 days for cycles 1 and 2, and 5 days for cycle 3. Both joint and muscle pain persisted 1 year after treatment in approximately half of responding patients. CONCLUSION: This study documents the significant incidence of TAPS in patients treated with docetaxel chemotherapy and shows a long-term persistence of the syndrome.

High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate.

PURPOSE: Abiraterone acetate (AA), used to treat metastatic castration-resistant prostate cancer (mCRPC), inhibits androgen biosynthesis by blocking cytochrome P450 (CYP) 17A1. It also inhibits other cytochromes involved in the metabolism of various widely used medications. As such, there is presumably a high potential for drug-drug interactions (DDIs) that can diminish the efficacy of AA or concurrent medications, or increase the risk of DDI-related adverse events (AEs). However, the scale of AA-associated DDIs is currently unknown. METHODS: We conducted a retrospective review of pharmacy records and electronic patient charts to retrieve individual drug histories and on-treatment AEs of mCRPC patients beginning AA therapy in a tertiary care setting. Potential DDIs were analyzed using two commercial databases, Lexicomp and Micromedex. RESULTS: Eighty-four informative patients were identified. Sixty-five patients (77 %) and 44 patients (52 %) were flagged for one or more potential DDIs by the Lexicomp and Micromedex databases, respectively. One hundred eighty-four potential DDIs were identified overall, with a median of 1 DDI per patient in both databases. Possibly due to rigorous DDI screening before AA treatment initiation, we did not identify a definite instance of DDI-related AEs. CONCLUSIONS: The use of commercial DDI databases suggests a substantial risk of potentially consequential DDIs in mCRPC patients undergoing AA therapy. However, prospective investigations with larger patient populations are required to better establish the clinical relevance of these DDIs.

The effects of denosumab on calcium profiles in advanced cancer patients with bone metastases.

OBJECTIVE: To retrospectively examine the incidence and management of hypocalcemia for patients with bone metastases treated with denosumab. METHODS: Patients who had a record of filling a prescription of denosumab for treatment of bone metastases at the outpatient pharmacy at the Odette Cancer Centre from May 2011 to February 2013 were included in the analysis. Demographic information, previous bisphosphonate usage, calcium and albumin values, and adverse events were obtained using the Sunnybrook Electronic Patient Record system (EPR) and the Oncology Symptom Control and Information Resource (OSCIR). Hypocalcemia was defined as a calcium value below 2.0 mmol/L within a 28-day±7-day window after the last injection of denosumab based on the Common Terminology Criteria for Adverse Events (CTCAE) grade 2 hypocalcemia. RESULTS: A total of 55 patients had record of a prescription for denosumab filled with an average age of 62 years (range 40 to 93 years), 18 (32.7%) were males and 37 (67.3%) were females. Twenty-nine (52.7%) patients had primary breast cancer, 12 (21.8%) prostate, 10 (18.2%) lung, and 4 (7.3%) with other types. Using CTCAE grading of hypocalcemia, 17 (32.7%) patients experienced grade 1, 4 (7.7%) patients grade 2, 4 (7.7%) patients grade 3, and 1 (1.9%) patient grade 4. The number of injections before the incident of hypocalcemia was a median of one injection (range 1 to 14). Time from the first hypocalcemia lab value to normocalcemia was a median of 33 days. CONCLUSIONS: This study found that 9 of 52 (17.3%) patients had at least one incidence of hypocalcemia of grade 2 or higher after receiving denosumab. Cautionary measures should be taken to avoid hypocalcemia in patients receiving denosumab.

Managing chemotherapy-induced nausea and vomiting in head and neck cancer patients receiving cisplatin chemotherapy with concurrent radiation.

BACKGROUND: The purpose was to retrospectively examine the anti-emetic regimens prescribed for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) for head and neck cancer patients receiving moderate- or high-emetogenic chemotherapy (MEC/HEC) along with concurrent radiation treatment at an outpatient ambulatory care center to determine the efficacy of anti-emetics prescribed. METHODS: Consecutive patients with head and neck cancers who initiated cisplatin chemotherapy with concurrent radiation treatment between January 2013 and June 2015 were investigated. Patients' anti-emetic use and occurrence of CINV was extracted from available clinical documentation. Patients were divided into two cohorts: CISPL-HIGH (n=161), and CISPL-WEEKLY (n=38). RESULTS: A total of 199 head and neck cancer patients (158 male, 41 female) were included in the analysis (mean age =59 years). In the CISPL-HIGH cohort, 33 males (26%) and 16 females (49%) experienced CINV. In the CISPL-WEEKLY cohort, four males (13%) and two females (25%) experienced CINV. Nausea occurred in 71 patients (62 HEC and 9 MEC). The odds of achieving complete response (no nausea or vomiting) were 3.5 (P<0.0016) times more likely for patients receiving MEC. Overall, the complete response rate for the prophylaxis in MEC and HEC was 61% and 31%, respectively. Anti-emetic changes occurred in 34% and 11% of patients receiving HEC and MEC, respectively. CONCLUSIONS: In the current study CINV control for patients receiving HEC was sub-optimal. Changes to our prophylactic antiemetic regimens may help improve patient outcomes.

Cost-Effectiveness Analysis of Different Sequences of the Use of Epidermal Growth Factor Receptor Inhibitors for Wild-Type KRAS Unresectable Metastatic Colorectal Cancer.

PURPOSE: Patients with unresectable wild-type KRAS metastatic colorectal cancer benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev), and epithelial growth factor receptor inhibitors (EGFRI). The most cost-effective regimen remains unclear. METHODS: A Markov model was constructed to examine the costs and outcomes of three treatment strategies: strategy A (reference strategy): EGFRI monotherapy in third line ([3L]; ie, first-line [1L]: Bev + FOLFIRI [FP + I] or FOLFOX [FP + O]; second line [2L]: FOLFIRI/FOLFOX; 3L: EGFRI); strategy B: EGFRI and I in 3L (ie, 1L: Bev + FOLFIRI/FOLFOX; 2L: FOLFIRI/FOLFOX; 3L: EGFRI + I); and strategy C: EGFRI in 1L (ie, 1L: EGFRI + FOLFIRI/FOLFOX; 2L: Bev + FOLFIRI/FOLFOX; 3L: best supportive care). Efficacy data of the treatments were obtained from the literature. Health system resource use information was derived from chart review and the literature. Using Euro-QOL 5 Dimensions, utilities were obtained by surveying medical oncologists and costs from the Ontario Ministry of Health and the literature. The perspective of the Canadian public health care system was used over a 5-year time horizon with a 5% discount in 2012 Canadian dollars. RESULTS: All three strategies had similar efficacy, but strategy C was most expensive. The incremental cost-effectiveness ratios (ICERs) for strategies B and C compared with A were 119,623 and 3,176,591, respectively. The model was primarily driven by the acquisition cost of the drugs. Strategy B was most cost effective when the willingness-to-pay threshold was > $130,000 per quality-adjusted life-year. Sensitivity analysis showed that strategy C would be cost-effective only when the progression-free survival of EGFRI is better than Bev in 1L with hazard ratio < 0.23 at willingness-to-pay of $150,000 per quality-adjusted life-year. CONCLUSION: First-line use of EGFRI in metastatic colorectal cancer is not cost effective at its current pricing relative to Bev.

Oral Anticancer Medication Adherence, Toxicity Reporting, and Counseling: A Study Comparing Health Care Providers and Patients.

PURPOSE: Oral anticancer medications (OACMs) have created new treatment opportunities, but also challenges for patients and practitioners. We aimed to compare health care provider (HCP) and patient perceptions on OACM adherence, toxicity reporting, and patient educational needs. METHODS: An online survey for HCPs and paper survey for patients were analyzed using descriptive statistics. Bivariate analysis using the χ(2) test was used for some questions. RESULTS: There were 169 HCP and 143 patient responses; 91% of patients reported taking their OACMs as prescribed more than 75% of the time, but only 40% of HCPs believed their patients were as adherent; 97% of HCPs believed patients reported their adverse effects some or most of the time; 61% of patients reported toxicities sometimes, often, or very often, but 30% never or rarely reported; 66% of HCPs believed patients did not report toxicity because of fear of treatment interruption, compared with 2% of patients. HCPs (53%) and patients (62%) both believed adverse effect tolerance was a common reason not to report. Most HCPs (70%) believed patients reported adverse effects first to a nurse. Patients seemed to report equally to nurses (42%) and oncologists (38%). Both HCPs and patients favored paper-based educational materials and call-back programs. CONCLUSION: This study highlights disparities in patient and HCP perceptions of OACM adherence principles and toxicity reporting. Opportunities for improved patient education are identified, particularly around reporting significant toxicities. Different HCPs may benefit from complimentary counseling tools to encompass the entire spectrum of patient needs and provider practice.

Retrospective review of the incidence of monitoring blood glucose levels in patients receiving corticosteroids with systemic anticancer therapy.

BACKGROUND: Corticosteroids are used adjuvant to certain chemotherapy regimens, either as an antiemetic, to reduce other side effects, or to enhance cancer treatment. Additionally, they are frequently used for symptom control in cancer patients with end stage disease. Corticosteroid use may induce hyperglycemia in approximately 20-50% of patients, which may negatively affect patient outcomes. OBJECTIVE: To determine the frequency of blood glucose monitoring in patients with and without diabetes receiving continuous corticosteroids with chemotherapy, and to determine the incidence of treatment-emergent abnormal blood glucose levels and steroid-induced diabetes mellitus (DM). METHODS: A retrospective review was conducted for 30 genitourinary (GU) cancer patients who were treated with continuous oral corticosteroids as part of their chemotherapy regimen. The Canadian Diabetes Association (CDA) criterion for diagnosis of diabetes was applied to categorize patients into two distinct groups, patients with diabetes and patients without diabetes. This categorization was made based on glucose measurements completed prior to commencement of corticosteroid therapy. Glucose monitoring was defined as receiving a laboratory blood glucose test before first chemotherapy administration along with a test within a week of each subsequent treatment cycle. The CDA criteria for diagnosis of pre-diabetes and diabetes was used to classify glucose levels as hyperglycemic. RESULTS: The mean incidence of blood glucose monitoring was 19% and 76% in patients with diabetes and patients without diabetes, respectively. Approximately, 40% of patients with diabetes required an adjustment to their diabetes management and a further 20% required hospitalization. Fifteen patients without diabetes received a fasting blood glucose test, of which 40% had abnormal blood glucose results; half of these fell into the pre-diabetic range and half in the diabetic range. Ten patients without diabetes were tested for diabetes using the CDA criteria for diabetes diagnosis during or after their chemotherapy, of which 30% developed diabetes. CONCLUSIONS: In order to optimize patient care, blood glucose levels should be monitored in all patients receiving continuous oral corticosteroids as part of their chemotherapy. Future studies should be conducted prospectively to determine the most effective manner of monitoring in order to implement screening guidelines and avoid unnecessary morbidity.

Time and labor costs associated with administration of intravenous bisphosphonates for breast or prostate cancer patients with metastatic bone disease: a time and motion study.

OBJECTIVES: To estimate, using a time and motion method, the time and labor costs associated with the administration of zoledronic acid and pamidronate in cancer patients with metastatic bone diseases. METHODS: During clinic visits for participating patients receiving intravenous zoledronic acid or pamidronate, all times and activities associated with the administration of bisphosphonates were recorded by a trained observer using a stopwatch and data recording forms. The total time associated with the administration of bisphosphonates was estimated and converted to labor costs by applying corresponding health care professional hourly wage rates plus the fringe-benefit rate. The costs were presented in 2011 Canadian dollars. RESULTS: A convenience sample of 37 patients from 2 hospital outpatient oncology clinics in Ontario and Quebec participated in the study. Nineteen patients were diagnosed with breast cancer and 18 with prostate cancer. The average patient age was 66 years, and patients had been diagnosed with cancer and metastatic bone disease for 8 years and 3 years, respectively. The times and costs associated with the administration of bisphosphonates for the 28 patients who did not receive concurrent chemotherapy during the scheduled clinic visits are also reported. The mean infusion time for patients receiving zoledronic acid was 20.6 minutes. With the use of ambulatory infusion devices, the mean infusion time of pamidronate was 23 minutes (limited to observations of patients who were seated during administration). In contrast, the mean infusion time using regular infusion devices was 162 minutes. The mean labor cost for administering zoledronic acid was $20. The mean labor cost for administering pamidronate was $10 using ambulatory infusion devices and $68 using regular infusion devices. CONCLUSION: The time burden to cancer patients with metastatic bone disease who receive intravenous bisphosphonates and the costs to the health care system are substantial, especially when regular infusion devices are used.

Baseline blood work before initiation of chemotherapy: what is safe in the real world?

INTRODUCTION: This is an observational study of patterns of practice of the timing of baseline blood work (BBW) before chemotherapy initiation. The primary objective was to evaluate the incidence of significant changes in laboratory values within 6 weeks before therapy. METHODS: All consecutive patients receiving chemotherapy within a 6-month period were analyzed retrospectively. Time interval between date of chemotherapy initiation and nearest blood work was calculated. Data from patients with one or more sets of values within 6 weeks were used to evaluate dosing changes. Changes in laboratory values collected closest to the date of chemotherapy and values collected before that but within 6 weeks were graded according to the National Cancer Institute's Common Toxicity Criteria. A change of ≥1 grade was considered clinically meaningful. RESULTS: Five hundred ninety-two patients were included. Median interval between BBW and initiation of chemotherapy was 4 days. Three hundred thirty-five patients had two or more sets of laboratory tests within the 6-week period, 33% of patients had a meaningful change in one or more values. The majority of changes occurred in hemoglobin (22%), ALT (14%), WBC (11%) and AST(10%), yet only 66% of patients had liver function tests as part of the BBW. CONCLUSIONS: Adherence to the institutional recommendation of BBW within 6 weeks was high. Baseline laboratory tests performed within 7 days of chemotherapy initiation would have detected nearly all significant changes; therefore, we suggest that this interval be tested in future randomized trials.