Decreasing drug waste, reducing drug costs, and improving workflow efficiency through the implementation of automated chemotherapy dose rounding rules in the electronic health record system

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To decrease drug waste and cost by implementing automated chemotherapy dose rounding rules in the electronic health record (EHR). Dose rounding of chemotherapy is a recognized method for reducing drug waste, and professional organizations have published guidelines recommending dose rounding when possible. Summary On the basis of current literature and guideline recommendations, Mayo Clinic developed system-wide consensus to allow dose rounding for biologic and chemotherapy agents to the nearest vial size if rounding resulted in the dose being within 10% of the originally calculated dose or to a convenient measurable volume, based on concentration of the drug, if rounding to the nearest vial size resulted in the dose being outside the 10% range. Oncology pharmacists reviewed and analyzed all drugs listed in the EHR used in injectable form for the treatment of cancer and developed dose rounding rules. The rules were implemented and applied at the dose calculation stage before provider signature. From January to June 2019, approximately 40,000 cancer treatment doses were administered. The rounding rules saved a total of 9,814 vials of drug, of which 5,329 were for biologic agents and 4,485 were for oncolytic drugs. This resulted in a total 6-month cost savings of $7,284,796 (in 2019 dollars; biologics, $5,727,402; oncolytics, $1,557,394). Conclusion Systematic implementation of dose rounding rules utilizing the EHR can result in significant reduction of drug waste and realization of savings.

Cryotherapy for Prevention of Taxane-Induced Peripheral Neuropathy: A Meta-Analysis

PurposeTaxanes are widely used in gynecological cancer therapy, however, taxane-induced peripheral neuropathy (TIPN) limits chemotherapy dose and reduces patients’ quality of life. As a safe and convenient intervention, cryotherapy has been recommended as a promising intervention in the recent clinical guidelines for the prevention of TIPN. Although there are a considerable number of studies which explored the use of cryotherapy in preventing chemotherapy-induced peripheral neuropathy (CIPN), there is insufficient large-scale clinical evidence. We performed a meta-analysis on the current available evidence to examine whether cryotherapy can prevent TIPN in cancer patients receiving taxanes.MethodsWe searched databases including PubMed, Embase, and Cochrane from inception to August 3, 2021 for eligible trials. Clinical trials that examined the efficacy of cryotherapy for prevention of TIPN were included. The primary outcome was the incidence of TIPN, and secondary outcomes were incidence of taxane dose reduction and changes in nerve conduction studies. The meta-analysis software (RevMan 5.3) was used to analyze the data.ResultsWe analyzed 2250 patients from 9 trials. Assessments using the Common Terminology Criteria for Adverse Events (CTCAE) score showed that cryotherapy could significantly reduce the incidence of motor and sensory neuropathy of grade≥2 (sensory: RR 0.65, 95%CI 0.56 to 0.75, p<0.00001; motor: RR 0.18, 95% CI [0.03, 0.94], p=0.04). When evaluated using the Patient Neuropathy Questionnaire (PNQ), cryotherapy demonstrated significant reduction in the incidence of sensory neuropathy (RR 0.11, 95% CI 0.04 to 0.31], p<0.0001), but did not show significant reduction in the incidence of motor neuropathy (RR 0.46, 95% CI 0.11 to 1.88, p=0.28). Cryotherapy was associated with reduced incidences of taxane dose reduction due to TIPN (RR 0.48, 95% CI [0.24, 0.95], p=0.04) and had potential to preserve motor nerves.ConclusionsCryotherapy is likely to prevent TIPN in patients receiving taxanes. High quality and sufficient amount of evidence is warranted.

Efficacy and Safety of Extended Use of Romiplostim Treatment for Chemotherapy-Induced Thrombocytopenia

Background: Chemotherapy induced thrombocytopenia (CIT) is common, adversely impacts chemotherapy relative dose intensity, and may adversely impact cancer control. There is no approved therapy for CIT. In our recent phase II study of solid tumor patients with CIT (Soff et al, J. Clin. Onc., 2019), romiplostim lead to correction of platelet counts in 85% of participants within 3 weeks. While on romiplostim maintenance, only 6.8% of participants experienced chemotherapy dose reduction or delay as a result of recurrent CIT within a minimum of two cycles of chemotherapy or 8 weeks. However, there is a lack of long-term data on the efficacy and safety of romiplostim in CIT. Objectives: This is an extension analysis of the phase II study for patients receiving romiplostim maintenance for 12 months or longer. Patients/Methods: In the phase II study, 44 patients successfully met the primary endpoint of correction of their platelet count within 3 weeks and resumed chemotherapy with romiplostim maintenance. 21 patients (48%) remained on romiplostim for 12 months or longer. Data were collected from one month prior to initiation of romiplostim to one month after the last dose of drug. Data extracted included complete blood count, chemotherapy doses and dates, romiplostim doses and dates, body weight, cancer diagnosis, age, gender, date of death and thrombotic events. Efficacy was demonstrated by persistent maintenance of platelet counts during long-term chemotherapy and avoidance of episodes of reduced chemotherapy dose intensity. Safety was assessed by two methods: tracking the rates of venous or arterial thrombosis; as well as development of marrow fibrosis and/or secondary hematologic malignancy. The mean romiplostim doses and lab values are calculated by month of study participation. Results: All participants had metastatic disease. Breast (N=6) and colorectal (N=6) were the most common cancers. No participant discontinued romiplostim therapy due to an adverse event or futility. One patient received romiplostim at our institution, but chemotherapy at an outside hospital; details of his chemotherapy were not available for this analysis. 14 of the 20 (70%) of the analyzable participants experienced no episode of CIT; 4 subjects experienced a single chemotherapy dose delay due CIT. No patient experienced multiple delays in chemotherapy due to CIT. Two patients required a chemotherapy dose reduction. The mean monthly platelet counts remained controlled throughout the period of analysis. (Figure 1A). The mean romiplostim doses were in the range of 3-5 mcg/kg through 35 months. There were insufficient participants beyond month 36 to allow meaningful interpretation of platelet counts or mean romiplostim doses. There was no evidence of adverse impact on absolute neutrophil count or hemoglobin levels (Figure 1B). No patient developed leukoerythroblastic changes indicative of marrow fibrosis, and no cases of secondary hematologic malignancy were identified. Two participants experienced thrombosis. One individual experienced a deep vein thrombosis. A second participant with an established history of congenital thrombophilia, experienced multiple tumor associated infarctions. The thrombotic events did not lead to discontinuation of participation in the trial for either participant. Of the 44 patients in the phase 2 study who resumed chemotherapy, 21 were alive at 12 months (48%) and 12 were alive at 24 months (27%). Conclusions: In this long-term analysis, romiplostim was effective and safe in the treatment of CIT with no evidence of drug resistance, marrow fibrosis, or secondary hematologic malignancy. The rates of thrombosis were no higher than expected for this patient demographic. There are some limitations to our analysis which includes our inability to accurately capture non-parenteral chemotherapy (oral or investigational agents) which were excluded from our analysis. We are unable to assess an impact on overall survival or cancer progression. However, the fact that half the participants were alive at 12 months and a quarter at 24 months is a reassuring signal. The analysis also is limited to the patients who were eligible for the initial phase 2 trial and corrected their platelet count within 3 weeks. Within these limitations, the extension study provides reassurance for long-term efficacy and safety of romiplostim treatment for CIT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Romiplostim is approved to increase platelet counts in ITP and pre-surgery. We are describing the results of a clinical trial.

Meta-Analysis of Chemotherapy-Induced (Febrile) Neutropenia and Chemotherapy Disruptions Associated with Same-Day Versus Standard (24-72h) Pegfilgrastim Administration in Non-Hodgkin Lymphoma Patients

Background: While the product label and international guidelines recommend pegfilgrastim administration 24-72 hours following completion of chemotherapy, increasingly clinicians administer pegfilgrastim using a same-day protocol. We performed a meta-analysis to compare the incidence of febrile neutropenia (FN), chemotherapy-induced neutropenia (CIN) grade 4, and CIN/FN-related chemotherapy delays and dose reductions in non-Hodgkin lymphoma (NHL) patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone with or without rituximab (R±CHOP) who were provided with pegfilgrastim on the same-day of chemotherapy versus the standard 24-72h post-chemotherapy time window. Methods: Six databases were searched for studies that compared same-day pegfilgrastim with the standard regimen in NHL patients. Given the low heterogeneity (I 2<50%, Cochrane Q test P>0.10, fixed-effect model was used to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for all outcomes of interest. Results: We identified 7 studies, including one clinical trial (Burris et al. 2010) and six retrospective cohort studies (Woods et al. 2010, Ibrahim et al. 2011, Karol et al. 2013, Cheng et al. 2014, Bartels et al. 2021, McBride et al. 2021), that evaluated same-day versus standard 24-72h administration of pegfilgrastim in NHL patients. Results were statistically non-significant for all outcomes (Figure 1): FN across all chemotherapy cycles (OR=1.48, 95%CI= 0.98-2.23, P=0.06, N of studies=7); FN after the first cycle (OR=1.98, 95% CI=0.80-4.90, P=0.14, N=4); CIN grade 4 across all cycles (OR=0.73, 95% CI=0.37-1.47, P= 0.38, N=3); CIN grade 4 after the first cycle (OR=2.58, 95%CI= 0.86-7.73, P=0.09, N=3); and chemotherapy dose delays or reductions (OR=2.25, 95%CI=0.42-11.97, P= 0.34, N=2). Conclusion: In this independent study, the likelihood of developing FN and CIN grade 4 in the first cycle or across all chemotherapy cycles, and the likelihood of chemotherapy dose delays or reductions were statistically not different in NHL patients treated with R±CHOP and administered pegfilgrastim same-day or 24-72h post-chemotherapy. In the setting of NHL treated with R±CHOP, administering pegfilgrastim on the day of completion of chemotherapy may be a safe and effective method of prophylaxis. Figure 1 Figure 1. Disclosures Alrawashdh: Genentech: Current Employment. McBride: BMS: Current Employment. Abraham: Matrix45, LLC: Current holder of individual stocks in a privately-held company.

The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis

There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX)(5-FU and oxaliplatin assessed separately), or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤ 80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer.

A Retrospective Evaluation of Chemotherapy Overdoses in Dogs and Cats

Chemotherapy overdoses (ODs) are severe complications that can occur following the use of antineoplastics. However, little is known about chemotherapy ODs in veterinary medicine. The goals of this retrospective study were to report the occurrence, type, and cause of known chemotherapy ODs in companion animal medicine. The American College of Veterinary Internal Medicine oncology and internal medicine listservs were solicited for chemotherapy OD cases in dogs and cats. An OD was defined as administration of a chemotherapy dose 10% higher than intended, or at a shorter interval than planned. Twelve non-anthracycline ODs in 11 dogs, and 3 cat ODs, were collected. Overdoses in dogs included carboplatin, cyclophosphamide, L-asparaginase, lomustine, mustargen, vincristine, and vinorelbine. The cat ODs included doxorubicin and vincristine. In dogs, the median OD was 2.1x (range: 1.2–10x) the intended dose. All dogs survived the OD and developed a variety of gastrointestinal and hematologic toxicities of varying grades. Both cats with a 2.4x vincristine OD died despite supportive care. The cat who received a 2x OD of doxorubicin survived the event, experiencing Veterinary Cooperative Oncology Group–common terminology criteria for adverse events (VCOG) grade I thrombocytopenia and anemia, and VCOG grade II neutropenia. Chemotherapy ODs appear to be rare in veterinary medicine and are typically 2–3xs the intended dose. Clinical effects include VCOG grade I and II gastrointestinal distress and VCOG grade III and IV hematologic effects. With appropriate supportive care, most patients will survive the event. Life-threatening events are more common in cats following vincristine ODs.

Ataxia-telangiectasia and combined hepatocellular-cholangiocarcinoma: A case report

Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by ataxia, cutaneous and ocular telangiectasia, impaired immunity with susceptibility to sino-pulmonary infections, radiation sensitivity and cancers particularly of haemato-lymphoid origin. Liver function tests abnormalities and elevated alfa feto-protein have been reported in A-T however there is no reported case of combined hepatocellular-cholangiocarcinoma (cHCC-CC) in literature. These tumours should be treated in similar fashion as in general population however reduction of chemotherapy dose might be helpful in decreasing chemo-toxicity.