Outpatient administration of paclitaxel, ifosfamide, and cisplatin (TIP) for germ cell tumor.

PURPOSE: The combination of paclitaxel, ifosfamide, and cisplatin (TIP) is frequently used for the treatment of metastatic germ cell tumors. Due to complex supportive care and infusion requirements, TIP is typically given in the inpatient setting. This analysis describes the development and implementation of a protocol for complete outpatient administration of TIP chemotherapy. METHODS: From July 2020 to June 2021, adults receiving TIP for germ cell tumor at University of Michigan Rogel Cancer Center were evaluated for outpatient administration. The primary outcome was number of inpatient bed days saved by giving outpatient TIP chemotherapy, with the goal of giving 75% of TIP cycles outpatient. Patients receiving outpatient TIP were also assessed for chemotherapy dose reduction or delays and acute toxicities of kidney injury, encephalopathy, and hemorrhagic cystitis. RESULTS: From July 2020 to July 2021, three patients received 13 cycles of TIP. Ten cycles (77%) were administered in the outpatient setting, resulting in a savings of 50 inpatient bed days in one year. No patients required a dose reduction or delay in chemotherapy or experienced acute kidney injury, encephalopathy, or hemorrhagic cystitis during outpatient TIP treatment. CONCLUSION: Despite logistic and supportive care challenges, TIP can be administered completely in the outpatient setting.

Evaluation of biliary toxicity in patients with hepatic artery infusion pumps.

PURPOSE: Identify risk factors for biliary toxicity in patients with colorectal liver metastases who received floxuridine (FUDR) via a surgically implanted hepatic artery infusion pump (HAIP). Describe the incidence of biliary toxicity and evaluate relevant patterns in the biliary toxicity cohort. METHODS: A single center, retrospective, case-control study included adult colorectal cancer patients with liver metastases who received at least one cycle of FUDR via a surgically implanted HAIP from 1 January 2017, to 1 October 2021. Patients were excluded if they had incomplete records, cholangiocarcinoma diagnosis, or received concurrent mitomycin and FUDR. Biliary toxicity criteria derived from existing HAIP literature were utilized to determine whether patients experienced biliary toxicity. Multiple variables were compared by univariate statistical analysis between the biliary toxicity and non-biliary toxicity cohorts to identify potential risk factors for development of FUDR-induced biliary toxicity. RESULTS: Out of 50 patients who had a HAIP implanted, 39 met the inclusion criteria. Five of the 39 patients (12.7%) included in the analysis met the pre-specified biliary toxicity criteria. No risk factors for biliary toxicity were identified. All five patients who developed biliary toxicity demonstrated elevations in alkaline phosphatase (ALP) prior to meeting the toxicity criteria. CONCLUSION: Biliary toxicity remains a significant and therapy-limiting consequence of FUDR administration. Rising ALP may be an early indicator of subsequent biliary toxicity. Future studies with more patients may identify risk factors that can facilitate risk mitigation strategies.

Solving coagulation conundrums: comparing prophylaxis strategies in adult patients receiving PEG-asparaginase.

PEG-asparaginase is a key component in treatment regimens for acute lymphoblastic leukemia (ALL). Major side effects include thrombosis and bleeding; however, there is currently no consensus on methods to prevent these complications. In this multi-center retrospective cohort study of 101 adults, we compared two prophylaxis strategies: cryoprecipitate and fresh frozen plasma (Cryo/FFP) versus cryoprecipitate and antithrombin (ATIII). The overall incidence of venous thromboembolism (VTE) was not significantly different between the two groups (19.7% for Cryo/FFP and 8.6% in Cryo/ATIII, p = 0.17), and neither was grade ≥3 bleeding (3% for Cryo/FFP and 11.4% for Cryo/ATIII, p = 0.18). Given the significant cost associated with ATIII without a clear benefit, a careful benefit and risk analysis should be considered before utilizing ATIII as a prophylaxis strategy to prevent thrombosis or bleeding following asparaginase administration.

Utility of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening in patients with acute myeloid leukemia (AML).

BACKGROUND: Current literature has demonstrated the utility of the MRSA nasal screen as a de-escalation tool to decrease unnecessary anti-MRSA antibiotic therapy. However, data on the applicability of this test in patients with hematologic malignancy is lacking. METHODS: This is a single-center, retrospective cohort study of patients with acute myeloid leukemia (AML) with or without a history of hematopoietic cell transplant (HCT), with pneumonia and MRSA nasal screening with respiratory cultures obtained. The primary outcome was to determine the negative predictive value (NPV) of the MRSA nasal screen for MRSA pneumonia. Secondary outcomes included sensitivity, specificity, positive predictive value (PPV) of the MRSA nasal screen and prevalence of MRSA pneumonia. RESULTS: Of 98 patients with AML and pneumonia, the prevalence of MRSA pneumonia was 4.1% with confirmed positive MRSA respiratory cultures observed in 4 patient cases. In patients with confirmed MRSA pneumonia, 3 had positive MRSA nasal screens while 1 had a false negative result, possibly due to a long lag time (21 days) between MRSA nasal screen and pneumonia diagnosis. Overall, the MRSA nasal screen demonstrated 75% sensitivity and 100% specificity, with a PPV of 100% and a NPV of 98.9%. CONCLUSIONS: Given the low prevalence, empiric use of anti-MRSA therapy in those AML and HCT patients with pneumonia may not be warranted in clinically stable patients. For patients in whom empiric anti-MRSA antibiotics are initiated, nasal screening for MRSA may be utilized to de-escalate anti-MRSA antibiotics in patients with AML with or without HCT.

Clinical controversies in the treatment of cancer-associated venous thromboembolism.

Cancer-associated venous thromboembolism (VTE) is a common complication of malignancy. Patients with cancer exhibit risk factors for both recurrent VTE and major or minor bleeding. Direct oral anticoagulants (DOACs) are an attractive treatment option; however, there is a lack of consensus among national guidelines for choice between DOACs and LMWH, agent selection, dosing strategy, and duration of anticoagulation. Characteristics of the thrombotic event, the malignancy, the patient, and the anticoagulant must be considered. A systematic search of online databases was performed to identify literature on the management of cancer-associated VTE. Multiple controversies remain surrounding the optimal treatment of cancer-associated VTE.

Impact of Extended-Interval Versus Standard Dosing of Zoledronic Acid on Skeletal Events in Non-Small-Cell Lung Cancer and Small-Cell Lung Cancer Patients With Bone Metastases.

BACKGROUND: Zoledronic acid every 4 weeks (Q4wk) reduces the incidence of skeletal-related events (SREs) in patients with metastatic lung cancer. Lung cancer patients were excluded from extended-interval dosing trials (every 12 weeks [Q12wk]) that demonstrated noninferiority of the 2 dosing schemes. To date, the optimal dosing of zoledronic acid in metastatic lung cancer remains unknown. OBJECTIVE: To determine whether zoledronic acid dosed Q12wk is similar to Q4wk dosing for prevention of SRE in patients with metastatic lung cancer. METHODS: A retrospective analysis was performed in patients with non-small-cell lung cancer and small-cell lung cancer with bone metastases who received Q12wk and Q4wk zoledronic acid. The primary outcome was incidence of SRE at 1 year. Secondary analyses included time to first SRE, overall survival (OS), incidence of osteonecrosis of the jaw (ONJ), kidney dysfunction, and hypocalcemia. RESULTS: A total of 34 patients received Q12wk and 46 patients received Q4wk zoledronic acid. Incidence of SRE at 1 year (Q12wk, 23.5%, vs Q4wk, 23.9%; 95% CI = -0.184 to 0.192; P = 0.968) and median time to SRE (not reached for either cohort; P = 0.530) did not differ. The Q12wk cohort had longer median OS (24.00 vs 8.97 months; P = 0.022). There were no differences in incidence of ONJ, kidney dysfunction, and hypocalcemia. CONCLUSION AND RELEVANCE: This is the first report examining extended-interval dosing of zoledronic acid in metastatic lung cancer. Incidence and time to SRE at 1 year were similar. This extended-interval dosing may be safe and reasonable for patients with lung cancer with bone metastases.

A comparison of response in the presence or absence of a delay in induction therapy with bortezomib, lenalidomide, and dexamethasone.

PURPOSE: Lenalidomide, bortezomib, and dexamethasone (RVd) has emerged as a preferred induction therapy in multiple myeloma (MM) in the United States. Due to lenalidomide's teratogenic risk, patients and prescribers must comply with a risk evaluation and mitigation strategy (REMS) program. The REMS program limits dispensing to certain third-party specialty pharmacies, whose average prescription fill times are longer than in-house specialty pharmacies. In practice, a delay in procurement of lenalidomide may mean that patients start therapy with only bortezomib and dexamethasone, delaying the start of more effective triplet therapy. The primary objective of this study is to determine if a delay from start of bortezomib and dexamethasone to start of triplet therapy with lenalidomide impacts rate of achievement of very good partial response (VGPR) after four cycles of RVd. METHODS: This was a single-center retrospective review of adults with newly diagnosed MM who received RVd induction therapy at University of North Carolina Medical Center between April 2014 and June 2017. Patients who started lenalidomide ≥10 days after bortezomib comprised the "Delay" group, while those who started lenalidomide concurrently with bortezomib or within 1-9 days after bortezomib comprised the "No Delay" group. The primary outcome was VGPR or better response rate after four cycles of RVd. RESULTS: Thirty-eight patients met inclusion criteria. Nine patients (23.7%) experienced any delay in initiation of lenalidomide, with a mean delay of 7.8 days (range 1-18). Four patients (10.5%) experienced a delay ≥10 days. No patients in the Delay group were of reproductive potential, compared to 8.8% in the No Delay group (p = 0.54). VGPR or better response rate did not differ between the Delay and No Delay groups (66.7% vs. 58.8%, p = 0.79). The mean number of lenalidomide prescriptions generated per RVd cycle was 1.35 (range 1-5, SD 0.74). CONCLUSIONS: This study did not demonstrate an effect on clinical response after delays ≥10 days between bortezomib and lenalidomide initiation. No patients in the delay group were females of reproductive potential, which is the primary target for increased safety behind the REMS program.

Comparison of Weight-Based Dosing Strategies for Intravenous Immunoglobulin in Patients with Hematologic Malignancies.

STUDY OBJECTIVE: Intravenous immunoglobulin (IVIG) is a weight-based therapy used to treat and prevent infections in patients with hematologic malignancies. IVIG doses were calculated traditionally using actual body weight (ABW). However, limited pharmacokinetic data suggest dosing strategies using ideal body weight (IBW) or adjusted body weight (adjBW) may be appropriate given the small volume of distribution of IVIG. Our objective was to compare the effectiveness of using a precision-dosing strategy (IBW or adjBW) with a traditional-dosing strategy (ABW) for IVIG in patients with hematologic malignancies or those undergoing hematopoietic stem cell transplant, as well as to perform an IVIG drug use analysis. DESIGN: Retrospective cohort study. SETTING: Academic medical center. PATIENTS: Between April 2014 and September 2016, 209 IVIG encounters met inclusion criteria for the primary outcome. Of those encounters, 125 were dosed using the traditional-dosing strategy, and 84 used the precision-dosing strategy. MEASUREMENTS AND MAIN RESULTS: The primary outcome was infection rate within 30 days of IVIG administration. Secondary outcomes included 60-day infection rate, immunoglobulin G (IgG)-level response (IgG higher than 400 mg/dl), and realized and potential IVIG savings. No difference in 30-day infection rate between precision- and traditional-dosing strategies was identified (15.5% vs 16%, respectively, p=0.823). Similarly, no difference was identified in the 60-day infection rate between groups (23.2% vs 19.8%, respectively, p=0.568). Levels of IgG obtained after IVIG repletion showed a treatment response rate of 86% in both groups. Use of a precision-dosing strategy achieved $2600/month in institutional savings with the opportunity for an additional $4600/month in savings with complete adherence to this dosing strategy. CONCLUSION: No differences in infection rate and IgG-level response were identified when a precision-dosing strategy was used. Implementation of an IVIG precision-dosing strategy provided institutional cost savings.