Sylvia Bartel

Medication safety in the ambulatory chemotherapy setting

Little is known concerning the safety of the outpatient chemotherapy process. In the current study, the authors sought to identify medication error and potential adverse drug event (ADE) rates in the outpatient chemotherapy setting.

Lack of efficacy of streptozocin and doxorubicin in patients with advanced pancreatic endocrine tumors.

Background:The combination of streptozocin and doxorubicin has been considered the standard palliative chemotherapy regimen in patients with advanced pancreatic endocrine tumors (PETs). However, a recent review failed to confirm high antitumor activity in patients with advanced PETs. Methods:We retrospectively reviewed the records of 16 consecutive patients who received streptozocin and doxorubicin for advanced PETs at Dana Farber/Partners Cancer Care institutions. Baseline patient characteristics, radiographic response to therapy, treatment-related toxicity, progression-free and overall survival were analyzed. Results:One patient demonstrated an objective partial response to therapy (objective response rate [ORR], 6%; 95% confidence interval [CI], 0–18%). Six patients achieved stable disease (38%; 95% CI, 14–62%) and 9 patients demonstrated disease progression on initial restaging (56%; 95% CI, 33–77%). The median progression-free survival and overall survival were 3.9 months (95% CI, 2.8–8.8) and 20.2 months (95% CI, 9.7–37.4), respectively. Conclusions:In this retrospective cohort, the combination of streptozocin and doxorubicin failed to demonstrate substantial antitumor activity in patients with advanced PET. Our findings underscore the need for new therapeutic options in this patient population.

Medication errors involving oral chemotherapy

Given the expanding use of oral chemotherapies, the authors set out to examine errors in the prescribing, dispensing, administration, and monitoring of these drugs.

Stratified Administration of Serotonin 5-HT3 Receptor Antagonists (Setrons) for Chemotherapy-Induced Emesis: Economic Implications

The serotonin 5-HT3 receptor antagonists or ‘setrons’ have become the standard of care for the prevention of chemotherapy-induced emesis (CIE) and are first-line therapy for acute CIE in healthcare organisations worldwide. However, their superior efficacy versus standard antiemetics comes at a significant cost. Currently, 3 agents are available in the US: ondansetron, granisetron and dolasetron.The most important treatment-related factor contributing to CIE is the emetogenicity of chemotherapy. The ability to customise, or stratify, the setron dose to match the emetogenic challenge of the chemotherapy administered has potential benefits, both clinically and economically. In adults, there is an appreciable amount of clinical literature addressing stratified administration; however, the amount of ‘hard’ economic data is rather limited. Intuitively, if clinical outcomes are equivalent, then stratified administration should be associated with economic benefits, as it generally promotes the use of doses lower than those recommended by the manufacturer. The literature strongly substantiates this for ondansetron, but is not as favourable for granisetron or dolasetron.As the rationale and justification for dose stratification is contained in the clinical literature, the authors have reviewed the pertinent literature supporting the clinical and economic benefits of dose stratification in both adult and paediatric patients. The authors also provide a discussion of various additional strategies that can be employed to ensure the appropriate and cost-effective use of setrons in real-world practice settings. These strategies include the use of lower doses than recommended by manufacturers, use for acute versus delayed phase emesis, enhancing the antiemetic efficacy by the addition of a corticosteroid, use of oral versus injectable formulations (when appropriate) and the implementation and use of local, national and international drug use guidelines.

Denosumab in hypercalcemia of malignancy: A case series

Background Denosumab is a nuclear factor-kappa ligand monoclonal antibody whose FDA-approved indications include treatment of osteoporosis, bone loss with certain anticancer hormonal agents, and prevention of skeletal-related events in patients with bone metastases from solid tumors. In clinical trials, the incidence of severe hypocalcemia has been reported as 3.1–10.8%. To date, case reports and two clinical trials have reported the use of denosumab in the management of hypercalcemia of malignancy. No reports of denosumab-induced hypocalcemia have been reported for the hypercalcemia of malignancy population. Methods We performed a retrospective chart review of all patients who received denosumab for hypercalcemia of malignancy to describe the effects of denosumab on calcium levels at our institution. Results Seven patients received doses of denosumab for hypercalcemia of malignancy. The most common tumor types were breast cancer (n = 3) and hematologic malignancies (n = 2). All patients had bone involvement. Two patients received single doses of 60 mg. The other five patients received 120 mg. The mean corrected calcium levels were 13.7 mg/dL and 12.24 mg/dL for the days of admission and denosumab administration, respectively (p = 0.1889). The mean corrected calcium level for the last known value was 9.92 mg/dL, while in house (p = 0.0016). Supportive care prior to denosumab included hydration (n = 7), bisphosphonates (n = 6), and calcitonin (n = 5). One patient had a calcium level of 6.6 mg/dL on day 4 after denosumab, requiring calcium supplementation and telemetry. Of the seven patients treated with denosumab for hypercalcemia of malignancy at our institution, six patients were discharged alive. Of these, one patient died two days after discharge. Last-known follow-up was a median of 26 days, range, 3–195, for all patients. Conclusions Denosumab helped decrease calcium in patients with hypercalcemia of malignancy. However, symptomatic hypocalcemia may result from denosumab in hypercalcemia of malignancy.

ASHP Guidelines on Preventing Medication Errors with Chemotherapy and Biotherapy

The purposes of these guidelines are to define best practices for the safe use of chemotherapy and biotherapy agents and to assist practitioners in improving their medication-use systems to prevent medication errors and patient harm from these agents. Although the guidelines are intended primarily

Predictive factors for all-trans retinoic acid-related differentiation syndrome in patients with acute promyelocytic leukemia

All-trans retinoic acid (ATRA) used for the treatment of APL can lead to the development of differentiation syndrome (DS), a potentially life threatening complication. Since ATRA is metabolized by cytochrome P450 (CYP) enzymes, we sought to identify drug interactions that might be associated with a higher risk for the development of DS in addition to other predictive factors related to the incidence of DS. We identified 60 consecutive patients with APL treated at our institution with ATRA from May 2004 until January 2010. Of the 60 patients identified, 29 (48%) developed DS within a median of 5 days (range 1-31) of ATRA initiation. We did not find any difference in overall incidence of DS whether patients were on concurrent CYP 2C8, 2C9 or 3A4 inhibitors, inducers or substrates. In multivariable analysis, higher peripheral blood blast counts on admission (p=0.04) as well as higher body mass index (p=0.003) were associated with developing DS. Out of the 29 patients with DS, there were 4 early deaths of which 2 were attributed to DS compared to no early deaths in the patients who did not develop DS (p=0.05). Regarding disease-related outcomes, only CR rate was different between patients developing DS versus those who did not develop DS.

Multicenter evaluation of a new closed system drug-transfer device in reducing surface contamination by antineoplastic hazardous drugs

Purpose Results of a study to evaluate the effectiveness of a recently introduced closed system drug‐transfer device (CSTD) in reducing surface contamination during compounding and simulated administration of antineoplastic hazardous drugs (AHDs) are reported. Methods Wipe samples were collected from 6 predetermined surfaces in compounding and infusion areas of 13 U.S. cancer centers to establish preexisting levels of surface contamination by 2 marker AHDs (cyclophosphamide and fluorouracil). Stainless steel templates were placed over the 6 previously sampled surfaces, and the marker drugs were compounded and infused per a specific protocol using all components of the CSTD. Wipe samples were collected from the templates after completion of tasks and analyzed for both marker AHDs. Results Aggregated results of wipe sampling to detect preexisting contamination at the 13 study sites showed that overall, 66.7% of samples (104 of 156) had detectable levels of at least 1 marker AHD; subsequent testing after CSTD use per protocol found a sample contamination rate of 5.8% (9 of 156 samples). In the administration areas alone, the rate of preexisting contamination was 78% (61 of 78 samples); with use of the CSTD protocol, the contamination rate was 2.6%. Twenty‐six participants rated the CSTD for ease of use, with 100% indicating that they were satisfied or extremely satisfied. Conclusion A study involving a rigorous protocol and 13 cancer centers across the United States demonstrated that the CSTD reduced surface contamination by cyclophosphamide and fluorouracil during compounding and simulated administration. Participants reported that the CSTD was easy to use.

A Phase I Trial of Surgical Resection and Intraoperative Hyperthermic Cisplatin and Gemcitabine for Pleural Mesothelioma

Introduction: The primary objective of this single‐institution phase I clinical trial was to establish the maximum tolerated dose of gemcitabine added to cisplatin and delivered as heated intraoperative chemotherapy after resection of malignant pleural mesothelioma. Methods: The extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators’ assessment of patient fitness and potential for macroscopic complete resection. Previously established intracavitary dosing of cisplatin (range 175–225 mg/m2) with systemic cytoprotection was used in combination with escalating doses of gemcitabine, following a 3‐plus‐3 design from 100 mg/m2 in 100‐mg increments. Results: From 2007 to 2011, 141 patients were enrolled and 104 completed treatment. The median age of those completing treatment was 65 years (range 43–85 years), and 22 (21%) were female. In the EPP arm (n = 59), 31 patients (53%) had the epithelioid histologic type and the median radiographic tumor volume was 236 cm3 (range 16–4285 cm3). In the P/D arm (n = 41), 29 patients (71%) had the epithelioid histologic type and the median tumor volume was 79 cm3 (range 6–1107 cm3). The operative mortality rate was 2%, and 35 and 22 serious adverse events were encountered among 27 patients (46%) and 16 patients (39%) in the EPP and P/D arms, respectively. Dose‐limiting toxicity (grade 3 leukopenia) was observed in two patients who were receiving 1100 mg/m2 of gemcitabine, thus establishing the maximum tolerated dose at 1000 mg/m2, in combination with 175 mg/m2 of cisplatin. The median overall and recurrence‐free survival times in treated patients were 20.3 and 10.7 months, respectively. Conclusions: Combination cisplatin and gemcitabine heated intraoperative chemotherapy can be administered safely and feasibly in the context of complete surgical resection of malignant pleural mesothelioma by EPP or P/D.

Chemotherapy and Medication Safety

Pediatric hematology oncology patients are at risk for medication and chemotherapy administration errors, which can lead to significant morbidity and mortality. Proper measurement and identification of medication errors are imperative to improvement, and chemotherapy error rates can be reduced through standardization of processes and continuous process improvement. To ensure sustainability, organizations should adopt a culture of safety and transparency.