Assessment of extended urine protein monitoring frequency in patients receiving bevacizumab

2020 ◽  
pp. 107815522094395
Author(s):  
Molly Schiffer ◽  
Lejla Zukovic ◽  
Sophia Hall ◽  
Man Yee Merl
Keyword(s):  
Package Insert ◽  
Patient Characteristics ◽  
Urine Collection ◽  
New Haven ◽  
Urine Protein ◽  
Medication History ◽  
Negative Results ◽  
Monitoring Frequency ◽  
Bevacizumab Treatment ◽  
Grade 3

Purpose Proteinuria monitoring is required for patients receiving bevacizumab. Nonetheless, the frequency of monitoring is not specified in the package insert. A 2014 quality improvement study performed at Yale New Haven Health System (YNHHS) found that proteinuria occurred in 15% (all grade) of the 162 patients evaluated. These results led to decreasing the frequency of proteinuria monitoring from every treatment to every other treatment. The objective of this study is to assess the safety of the extended interval for urine protein (UP) monitoring. Methods Patients receiving at least four bevacizumab treatments at YNHHS from January to June 2017 were randomly selected and retrospectively reviewed. The following data were collected: baseline patient characteristics, comorbidities, medication history, and proteinuria monitoring. The grade, prevalence and management of proteinuria were evaluated. The minimum necessary sample size was determined to be 384 treatments to achieve a 95% confidence interval. Results Fifty-five patients and 388 bevacizumab treatments were evaluated. Urine protein was assessed in 52.5% of treatments. The incidence of proteinuria among patients was 7.2% (grade 2) and 0% (grade 3). Cumulative dose and the number of total bevacizumab doses did not affect the timing for onset or severity of proteinuria. Two patients with UP ≥ 2+ were further monitored using a 24-h urine collection test with negative results. No treatments were held due to proteinuria. Conclusion Monitoring proteinuria every other treatment does not increase the frequency of adverse events. Urine protein is now monitored prior to every third bevacizumab treatment, reducing unnecessary labs and chair time.

Routine proteinuria monitoring for bevacizumab in patients with gynecologic malignancies

2016 ◽  
Vol 22 (6) ◽  
pp. 771-776 ◽  
Author(s):  
Catherine S Lee ◽  
Laura M Alwan ◽  
Xiaocui Sun ◽  
Katherine A McLean ◽  
Renata R Urban
Keyword(s):  
Risk Factors ◽  
Gynecologic Oncology ◽  
Cost Savings ◽  
Retrospective Chart Review ◽  
Creatinine Ratio ◽  
Gynecologic Malignancies ◽  
Urine Protein ◽  
Potential Cost ◽  
Bevacizumab Treatment ◽  
Grade 3

Background Proteinuria leading to nephrotic syndrome is a rare adverse event arising from treatment with bevacizumab. There is limited evidence to guide the frequency and appropriate test for monitoring for proteinuria. The purpose of this study was to determine the prevalence and severity of proteinuria during bevacizumab administration to patients with gynecologic malignancies, and to evaluate risk factors associated with this toxicity; a secondary objective was to evaluate the cost of routine proteinuria monitoring to assess for opportunities of cost containment that could change clinical practice. Methods A retrospective chart review was performed at an academic gynecologic oncology clinic. Women over 18 years of age with a diagnosed gynecologic malignancy were evaluated for the development of proteinuria while receiving bevacizumab treatment as measured by a urine protein-to-creatinine ratio. Patient and disease-specific risk factors were evaluated using logistic regression to determine correlations of risk factors to development of proteinuria. Cost assessment was performed using institution-specific data for urine laboratory tests. Results Eighty-nine patients were identified, and the overall prevalence of proteinuria of any grade was 35%. The mean number of bevacizumab cycles was 13 (2–64 cycles). The majority of patients experienced grade 1 proteinuria (70%, 62 patients). Grade 3 proteinuria was observed in two patients (2%). There was a trend toward increased bevacizumab cycles associated with increased grade proteinuria ( p = 0.053), however there were no factors significantly associated with the development of proteinuria as measured by urine protein-to-creatinine ratio. Conclusion Monitoring of urine protein-to-creatinine ratios with each cycle may be unnecessary due to the low prevalence of grade 3 proteinuria observed. Additionally, urine protein-to-creatinine ratios may not provide adequate assessment of proteinuria toxicity associated with bevacizumab therapy. Potential cost savings opportunities for the institution can be realized with a cost-reductive monitoring algorithm that will utilize less costly laboratory techniques for patients at high risk of developing proteinuria.

Prevalence of discordant QTc values among cancer patients by the Bazett, Fridericia, and Framingham formulae: Evidence for a standardized approach.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6575-6575
Author(s):  
P. Christopher Parish ◽  
Benyam Muluneh ◽  
Charles Hicks ◽  
Brian Jensen ◽  
Joshua F. Zeidner ◽  
...  
Keyword(s):  
Adverse Event ◽  
Cancer Patients ◽  
Clinical Management ◽  
Package Insert ◽  
Patient Characteristics ◽  
High Rate ◽  
Correction Formula ◽  
Life Threatening ◽  
Potential Impact ◽  
Grade 3

6575 Background: Many chemotherapies have the potential to prolong the QT interval, requiring monitoring of the corrected QT (QTc) to prevent life-threatening arrhythmias. Most clinical guidelines recommend adjusting/holding chemotherapy with Grade 3 or higher toxicity by CTCAE (QTc≥500). Several formulae are used for QTc monitoring including Bazett, Fridericia, and Framingham. The most commonly used formula, Bazett, is well-documented to result in inappropriately high QTc values although the potential impact of this overcorrection on cancer treatment is unknown. We aimed to describe the prevalence of QTc prolongation among cancer patients and the effects on CTCAE adverse event grading by various QTc formulae to determine the potential impact on clinical management. Methods: We performed a single-center retrospective analysis of QT values from electrocardiograms (ECGs) collected January 2010-April 2020 and evaluated associations between QTc values, medications, and patient characteristics. QTc prolonging agents were determined by FDA package insert and cross-referenced with CredibleMeds.org. Results: 20,017 ECGs were evaluated. 18.6% (3,730) met ACC/ACCF/HRS criteria for prolonged QTc by ≥1 QT correction formula (either Bazett, Fridericia, or Framingham). 7.5% (1,494) were prolonged with all three formulae, and 8.6% (1,635) were prolonged only with Bazett. The CTCAE classification using the Bazett formula differed from both Fridericia and Framingham in 37.9% (7,583) of the ECGs. In contrast, Fridericia and Framingham formulae resulted in the same CTCAE classification in 94.5% (18,912). Of 1,789 ECGs classified as Grade 3 toxicity by Bazett, 72.0% (1,288, 6.4% of all ECGs) were classified as Grade 2 or less by both Fridericia and Framingham. 12.0% (2,340) of all ECGs were taken from patients (n = 421) on 24 different QT-prolonging chemotherapies. In 38.8% (909) of the ECGs, the CTCAE classification using the Bazett formula differed from both Fridericia and Framingham while use of Fridericia and Framingham formulae resulted in the same classification in 93.0% (2,176) of the ECGs. Of 293 ECGs classified as Grade 3 toxicity by Bazett, 65.2% (191) were classified as Grade 2 or less by both Fridericia and Framingham. Conclusions: To our knowledge, this is the largest analysis of discrepancies between different QTc formulae in patients receiving chemotherapy. These findings demonstrate an unacceptably high rate of discordance between formulae. Discordant data can lead to inconsistent clinical management and adverse event grading underscoring the urgent need to standardize QTc monitoring and reporting. These findings support the discontinuation of the routine use of the Bazett correction formula among cancer patients as CTCAE Grade 3 reporting from the Bazett formula is unreliable in over 65% of cases.

Incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis

2016 ◽  
Vol 23 (3) ◽  
pp. 179-184 ◽  
Author(s):  
Prakirthi Yerram ◽  
Shraddha Kansagra ◽  
Osama Abdelghany
Keyword(s):  
Risk Factors ◽  
Bone Metastasis ◽  
Calcium Supplementation ◽  
Common Side Effect ◽  
New Haven ◽  
Study Population ◽  
Skeletal Related Events ◽  
Kidney Insufficiency ◽  
Grade 3 ◽  
Haven Hospital

Background Denosumab therapy is commonly used for the prevention of skeletal-related events in patients with bone metastasis. However, a common side effect of denosumab is hypocalcemia. Objective The aim of the study is to determine the incidence of hypocalcemia in patients receiving denosumab for prevention of skeletal-related events in bone metastasis and evaluate risk factors for developing hypocalcemia. Methods This was a retrospective medication use evaluation reviewing the incidence of hypocalcemia in patients receiving outpatient denosumab for prevention of skeletal-related events at Yale–New Haven Hospital. Additionally, various risk factors were reviewed to determine their risk of developing hypocalcemia. Results As per Common Terminology Criteria for Adverse Events v4.03, of the 106 patients included in the study population, 37 (35%) patients had an incidence of hypocalcemia within 30 days of denosumab administration. Fourteen patients (13.2%) had an incidence of grade 1, 13 patients (12.3%) had an incidence of grade 2 hypocalcemia, and 7 patients (6.6%) had an incidence of grade 3 hypocalcemia. Grade 4 hypocalcemia occurred in three (2.8%) patients. Calcium supplementation did not decrease the risk of developing hypocalcemia. Patients who had one or more episodes of acute kidney insufficiency were at a higher risk of developing hypocalcemia (odds ratio = 7.5 (95% confidence interval = 1.8–36.3), p = 0.001). Conclusion This study found that the overall incidence of hypocalcemia and severe hypocalcemia was higher than reported in clinical trials. Additionally, calcium supplementation did not have an effect on incidence of hypocalcemia, while patients who experienced acute kidney insufficiency while on denosumab had a higher likelihood of developing hypocalcemia.

scholarly journals Fludarabine Melphalan Versus Fludarabine Treosulfan As Reduced Intensity Conditioning Regimens in Allogeneic Hematopoietic Stem Cell Transplant - a Retrospective Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4493-4493
Author(s):  
Akanksha Chichra ◽  
Lingaraj Nayak ◽  
Rushabh Kothari ◽  
Siddhesh Arun Kalantri ◽  
Avinash Bonda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Gvhd ◽  
Patient Characteristics ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Entire Cohort ◽  
Conditioning Regimens ◽  
Grade 3 ◽  
Haplo Group ◽  
Very High

Introduction Allogeneic hematopoietic stem cell transplantation (AHSCT) has evolved as a curative therapy for various hematological malignancies. Regimen-related toxicity and transplant-related mortality (TRM) preclude the use of myeloablative conditioning (MAC) regimens in older and unfit patients. Reduced intensity conditioning (RIC) regimens have enabled AHSCT in such patients. There is a recent rise in use of RIC regimens even in younger patients in view of decreased toxicity and equal efficacy as reported in some studies. Fludarabine + Melphalan (FM) and Fludarabine + Treosulfan (FT) are 2 such regimens. There are no prospective randomised comparisons between these regimens. We retrospectively analysed these 2 regimens for toxicities and outcomes. Methods This is a retrospective single centre analysis of all consecutive patients with haematological cancers who received either FM or FT from April 2008 to December 2018. The entire cohort was divided into two groups - Matched Sibling Donor (MSD)/Matched Unrelated Donor (MUD) and Haploidentical (Haplo) transplants for analysis. We compared patient characteristics, toxicities and outcomes in both the groups based on conditioning regimen. The FT regimen consisted of fludarabine (30 mg/m2 on days − 6 to − 2) combined with treosulfan (12-14 gm/m2 on days − 6 to − 4) with or without 2 Gy TBI on day-1. The FM regimen consisted of fludarabine (30 mg/m2 on days − 7 to − 3) combined with melphalan (140 mg/m2 on day -1).Prophylaxis for GVHD consisted of calcineurin inhibitor (CNI) plus methotrexate (MTX)or mycophenolate mofetil (MMF) in MSD/MUD. Rabbit ATG (2.5-5 mg/kg) was used for MUD. Haplo transplant patients received post-transplant cyclophosphamide with CNI and MMF. Comorbidities were scored according to the HCT-CI. Disease Risk Index(DRI) and EBMT score were recorded for all patients. Neutrophil (NE) and platelet engraftment (PE) were defined as per standard criteria. Early toxicity after AHCT was graded according to CTCAE version 4. Total parenteral nutrition (TPN) was used in patients as per the physician's discretion. Acute GVHD and chronic GVHD were recorded according to standard criteria. All patients underwent chimerism studies at day 15, 30 and then monthly for 1 year. Mixed chimerism was defined as > 5% to < 95% donor chimerism. The toxicities in various arms were compared by Chi-square test or Fisher exact test, while OS was calculated by Kaplan Meier method and the survival probabilities were compared using log-rank test. Competing risk analysis was used to calculate cumulative incidence of relapse and TRM. Results The study included 138 patients, 98 males and 40 females. The diagnoses were AML- 53, ALL- 30, MDS/MPN- 49 and lymphoma -6. Patient characteristics are outlined in Table 1. MSD/MUD transplants were 105 (FM- 94; FT-11); 33 were Haplo (FM-17; FT-16) transplants. PBSC was the stem cell graft in 136 (99%) patients. In both MSD/MUD and Haplo groups, there were no significant differences in median age, gender, pre transplant CMV status, HCT-CI and EBMT score between the two conditioning regimens. In MSD/MUD group, significantly more patients had high/very high DRI in FT arm (45% vs 17%; P=0.056) Comparison of engraftment and toxicity variables of both FM and FT arms are outlined in Table 2. In MSD/MUD group, 44 (47%) patients in FM arm had grade 3/4 oral mucositis compared to 1 (9%) in FT arm (P=0.02). Corresponding numbers were 7 (41%) and 1 (6%) in Haplo group (P=0.039). Grade 3/4 diarrhoea was higher in the FM vs FT arm of Haplo group (41% vs 6%; P=0.039) but not in the MSD/MUD cohort. More patients received TPN in the FM arms of both MSD/MUD and Haplo groups (Table 2). Incidence of grade III-IV acute GVHD was higher in FT vs FM in MSD/MUD group (27% vs 17%; P=0.04). The median follow up of entire cohort was 4.8 years. The OS (figure 1) at 5 years was 62% in FM arm of MSD/MUD group vs 53% in FT arm (P=NS). Similarly OS (figure 2) at 5 years was 41% and 28 %( P=NS) in FM and FT arms respectively of Haplo group. The cumulative incidence of TRM and relapse at 2 years were not different in FM and FT arms of both MSD/MUD and Haplo groups (Table 2). Conclusion Grade 3 and 4 oral mucositis and diarrhoea were significantly less with FT than FM in both MSD/MUD and Haplo groups. FT provided comparable outcomes to FM in the MSD / MUD group in spite of having higher proportions of patients with high / very high DRI. Prospective randomised studies are required to compare various RIC regimens. Disclosures No relevant conflicts of interest to declare.

scholarly journals ACTR-32. NRG ONCOLOGY RTOG 1205: RANDOMIZED PHASE II TRIAL OF CONCURRENT BEVACIZUMAB AND RE-IRRADIATION VS. BEVACIZUMAB ALONE AS TREATMENT FOR RECURRENT GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi20-vi20 ◽  
Author(s):  
Christina Tsien ◽  
Stephanie Pugh ◽  
adam Dicker ◽  
Jeffrey Raizer ◽  
Martha Matuszak ◽  
...  
Keyword(s):  
Objective Response ◽  
Patient Characteristics ◽  
Recurrent Glioblastoma ◽  
Rank Test ◽  
Significance Level ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Recurrent Gbm

Abstract This study sought to determine whether re-irradiation (ReRT) and concurrent bevacizumab (BEV) improves overall survival (OS) compared to BEV alone in recurrent glioblastoma (GBM). Patients (pts) were randomized 1:1 to ReRT (35 Gy/10 fractions) plus BEV (IV 10 mg/kg q2 wks) vs. BEV alone. With 160 pts, there was 80% power to detect a 31% reduction in death hazard for BEV+RT at a one-sided significance level of 0.10 using a log rank test. OS and PFS were estimated by Kaplan-Meier and HRs estimated by exact binomial distribution. Objective response was assessed using MacDonald and RANO criteria. From 11/2012 to 4/2016, 182 pts were randomized, with 170 eligible, analyzable pts. 11 pts did not receive protocol treatment. Patient characteristics (age, KPS, re-resection rates) were balanced between arms. Median f/u for censored pts was 12.8 months (mos; min-max, 0.03–52.8). BEV+ReRT did not improve OS vs BEV alone, with median OS of 10.1 vs 9.7 mos, (HR=0.98, 95% CI=0.70–1.38, p=0.46). Median PFS for BEV+RT and BEV was 7.1 vs. 3.8 mos, respectively (HR=0.73, 95% CI=0.53–1.0, p=0.051). BEV+ReRT improved 6-mo PFS rate (PFS6): 54 vs. 29%, (HR=0.42, 95% CI=0.34–0.5, p=0.001). Overall, treatment was well tolerated: 5% acute and 0% delayed grade 3+ treatment-related AE. Most patients died from recurrent GBM. CONCLUSION: RTOG 1205 is the first, prospective, randomized multi-institutional study to evaluate the safety and efficacy of ReRT in recurrent GBM using modern RT techniques. Overall, ReRT was shown to be safe and well tolerated. BEV+ReRT did not demonstrate a benefit in OS but an improved PFS6, and clinically meaningful PFS improvement. Molecular correlates of response analyses are ongoing. Funded by U10CA180868, U10CA180822 from the National Cancer Institute.

Retrospective Analysis of Fractionated High-Dose Melphalan (F-MEL) and Bortezomib-Thalidomide-Dexamethasone (VTD) with Autotransplant (AT) Support for Advanced and Refractory Multiple Myeloma (AR-MM).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3102-3102 ◽  
Author(s):  
Mauricio Pineda-Roman ◽  
Michelle H. Fox ◽  
Klaus A. Hollmig ◽  
Elias J. Anaissie ◽  
Frits van Rhee ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Single Agent ◽  
Patient Characteristics ◽  
Median Number ◽  
Outpatient Setting ◽  
High Dose ◽  
Life Threatening ◽  
Grade 3 ◽  
High Dose Melphalan ◽  
Asco 2006

Abstract Background: MEL is an effective and safe AT regimen for MM, usually administered as a single dose at 200mg/m2; mucositis is dose-limiting. There is recent pre-clinical and clinical evidence of synergistic interaction of MEL with both immuno-modulatory agents (thalidomide, MPT [Palumbo, Lancet, 2006], lenalidomide, RMP [Palumbo, ASCO, 2006]) and with the first-in-class proteasome inhibitor, bortezomib (VelcadeR) (VMP, Mateos, ASCO, 2006). We previously reported on the marked activity of VTD in AR-MM, even in a setting of resistance to single agent thalidomide and bortezomib (Blood, January, 2004). In a clinical setting of AR-MM, we administered IV MEL after bortezomib (V) on days 1, 4, 7 +/− d 10, along with daily thalidomide (T) and dexamethasone (D), in order to achieve maximum pharmacological synergy of all 4 drugs. Patients and Methods: A retrospective analysis was performed of 22 patients with AR-MM, who were treated with the F-MEL-VTD regimen with the following MEL fractions: 3-F at 50–80mg/m2 for total doses of 150–240 mg/m2, 18 patients; 4-F at 50–60mg/m2 for total doses of 200–240 mg/m2, 4 patients; 5-F at 15–50 mg/m2 for total doses of 150–250 mg/m2, 2 patients. V was given at doses of 1.0–1.3 mg/m2 immediately preceding each MEL fraction; T was dosed at 100–200 mg/d from day 1 until the last day of MEL; D was given at 20–40 mg on the day of and after V and MEL. Two patients received 2 cycles of F-MEL-VTD, so that 24 courses could be evaluated. Results: Patient characteristics included a median age of 61yr (range, 46–75yr), median creatinine of 0.85mg/dL (range, 0.6–1.9mg/dL); abnormal cytogenetics (CA) were present in 15/22 (68%) - typifying the high-risk nature of their disease; the median number of prior regimens was 6 (range, 1–14); prior AT: 0 in 3 patients, 1 in 11, 2 in 8 and 3 in 1 patients. F-MEL-VTD was initiated in the outpatient setting in 15, only 3 of whom required subsequent hospital admission. Toxicities included grade 3–4 diarrhea mainly due to C. difficile in 8 (33%) and oral mucositis > grade 2 in only 1; grade 3 fever in 3 (12%) with Aspergillus pneumonia in 2 patients; no transplant-related mortality. Hematopoietic recovery was excellent with median times to ANC>500/microL of 10 days (range, 8–19d) and platelets > 50.000/microL of 17 days (range, 10–24d); 2 patients receiving 1.88 and 1.95 x 106 CD34+ cells/kg failed to recover platelet counts to >50.000/microL. Response rates were measured at 6 weeks, using Blade criteria: CR, 11 (46%) with an additional 3 achieving near-CR (>=n-CR, 59%); PR, 4 (17%); the remainder 24% had transient or no response. Conclusion: F-MEL-VTD was remarkably well tolerated, permitting total MEL dose escalation to > 200mg/m2 in 13 of 22 patients, without incurring grade >2 stomatitis in the majority of patients. Due to the protracted administration involved in this regimen, the median duration of neutropenia was 10 d (range, 8 to 19d) with life-threatening infections observed in only 2 patients. These encouraging data form the basis for a randomized trial of VTD followed by standard 1-F MEL versus 3-F MEL with VTD preceding each MEL dose.

Economic Impact of Adverse Events in Chronic Myelogenous Leukemia: A Cost of Treatment Analysis of Dasatinib.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3309-3309 ◽  
Author(s):  
Sarah Y. Liou ◽  
Kimbach T. Tran ◽  
Jennifer M. Stephens ◽  
Nneka C. Onwudiwe ◽  
Marc F. Botteman
Keyword(s):  
Adverse Events ◽  
Economic Impact ◽  
Chronic Myelogenous Leukemia ◽  
Package Insert ◽  
Myelogenous Leukemia ◽  
Cost Of Treatment ◽  
Blast Phase ◽  
Total Cost ◽  
Grade 3

Abstract OBJECTIVES: With a greater focus on costs in today’s health care markets, it is important to evaluate overall costs and quality of care associated with new therapies in cost-effectiveness analyses. Adverse events (AEs) associated with cancer therapies often result in substantial economic costs and negative impacts on patient quality of life. AEs may also affect adherence to therapy and result in suboptimal treatment outcomes. Important AEs of dasatinib in chronic myelogenous leukemia (CML) patients who are resistant to imatinib include neutropenia, thrombocytopenia, anemia, gastrointestinal hemorrhage, central nervous system hemorrhage, and fluid retention leading to effusions and heart dysfunction. This study evaluated the total cost of treatment with dasatinib in patients with chronic, accelerated, and myeloid blast phase CML, taking into account both drug and AE-associated costs. METHODS: A literature-based economic model was developed to examine the short-term potential impact of AEs in patients with CML treated with dasatinib. The incidence rates of Grade 3/4 AEs were obtained from the SPRYCEL™ (dasatinib) package insert. The AEs were assumed to occur within the first 6 months of treatment. The costs associated with the AEs were obtained from published medical literature and the 2003 Healthcare Cost and Utilization Project database of mean hospital charges by principal diagnosis, converting to costs using a Medicare cost-to-charge ratio of 0.55. Dasatinib dosing assumptions were based on the FDA briefing documents of the SPRYCEL™ filing submission presented at the June 2, 2006 Oncology Drug Advisory Committee meeting. The initial dose for dasatinib was 70 mg twice daily based on the package insert. Patients were assumed to remain on treatment for 6 months. However, dose interruption of 7–14 days during the first 3 months of treatment and dose reduction to 50 mg twice daily in the second 3 months of treatment were assumed in 46–55% and 9–10% of patients, respectively. Drug costs were based on wholesale acquisition cost. Univariate and multivariate sensitivity analyses were conducted. All costs were adjusted to 2006 U.S. dollars using the medical care component of the consumer price index. RESULTS: In the base case analysis, the expected 6-month per-patient cost of treatment for dasatinib was $31,528 for chronic phase, $44,340 for accelerated phase, and $48,666 for myeloid blast phase. Six-month drug cost alone was $22,284 per patient in each phase. Grade 3/4 AEs accounted for approximately 29%, 50%, and 54% of the total cost of care for chronic, accelerated, and myeloid blast phases, respectively. Sensitivity analysis showed that the 6-month cost of Grade 3/4 AEs may range from $5,235–$10,696 for chronic, $16,109–$23,723 for accelerated, and $12,971–$27,551 for myeloid blast phases. Primary cost drivers were the hematologic AEs. CONCLUSIONS: This study provides an estimate for the total cost of treatment with dasatinib that considers treatment costs for severe AEs associated with therapy. These results highlight the importance of including treatment-related AEs in addition to drug costs when assessing the economic value of treatment options for CML. Future studies should expand the time horizon of the analysis and include recurring AEs to more comprehensively evaluate the overall economic impact of AEs with dasatinib.

Phase II Trial of Standard Dose Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (CHOP) and Rituximab (R-CHOP) Plus Bevacizumab for Advanced Stage Diffuse Large B-Cell (DLBCL) NHL: Southwest Oncology Group Study S0515

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 591-591 ◽  
Author(s):  
Alison T. Stopeck ◽  
Joseph M Unger ◽  
Lisa M. Rimsza ◽  
Brent Farnsworth ◽  
Michael LeBlanc ◽  
...  
Keyword(s):  
Adverse Events ◽  
Standard Dose ◽  
Immunohistochemical Analysis ◽  
Patient Characteristics ◽  
Tissue Microarrays ◽  
Left Ventricular ◽  
Serious Adverse Events ◽  
Significant Toxicity ◽  
Southwest Oncology Group Study ◽  
Grade 3

Abstract Abstract 591 Introduction: VEGF and VEGF receptors (VEGFR) are frequently over-expressed in DLBCL. Elevated levels of circulating VEGF have also been associated with a worse prognosis and resistance to chemotherapy. This trial was initiated to determine if the addition of anti-VEGF targeted therapy to standard R-CHOP would improve PFS without adding significant toxicity in previously untreated patients with stage III, IV or bulky stage II DLBCL. Methods: 64 eligible patients were treated with standard dose R-CHOP plus bevacizumab administered at 15mg/kg on day1. Patients received therapy every 21 days for a maximum of 8 cycles. Both biologics were administered prior to chemotherapy. Pretreatment tumor biopsies from 40 patients were submitted for construction of tissue microarrays for VEGF/VEGFR immunohistochemical analysis. Two 1 mm tissue cores were assessed for each DLBCL specimen and expression of VEGF and VEGFR scored on a scale of 0 (no expression) to +3 (strong expression) by 2 pathologists. Both lymphoma and endothelial cell (blood vessel) staining was assessed with the higher score being recorded. Results: 73 patients were enrolled with 9 patients found ineligible, the majority (n = 7) secondary to incorrect histology. Patient characteristics for the 64 eligible patients included: median age 68 years with 77% of the patients over 60 years (age range: 22–85), 44 males, IPI scores: 3 low, 22 low-intermediate, 29 high-intermediate, and 8 high. Median follow-up is 2.0 years. Based on prior studies, and adjusted for the observed IPI factor frequencies seen in this study, the projected 1 year historical PFS rate in this population would be 71%, while the observed 1 year PFS estimate was 77% (95% CI: 66 – 87%). The PFS estimate at 2-years was 69% (95% CI: 57 – 80%). The 1 and 2 year overall survival estimates were 86% and 79%, respectively. Among all patients (including ineligibles), a total of 30 patients experienced 40 serious adverse events (SAE) while on study. The majority of SAE were hematologic, but also included 2 patients with sudden death, 5 patients with GI perforations (4 occurring after cycle 1), and 5 patients with grade 3 or 4 thrombotic events. Additional adverse events of interest included 7 patients who developed hypertension (4 patients with grade 3), and 13 patients who developed grade 2 or 3 left ventricular dysfunction. VEGF expression was observed in 98% (IHC scoring: +1 in 18%, +2 in 38%, and +3 in 43%) of lymphoma cells and VEGFR was expressed in 95% (IHC scoring:+1 in 28%, +2 in 40%, and +3 in 28%) of blood vessels by immunohistochemistry analysis. Conclusions: Despite high protein expression of VEGF and VEGFR in newly diagnosed DLBCL specimens, the addition of bevacizumab to standard R-CHOP chemotherapy did not significantly improve PFS from expected results with R-CHOP alone. Although the observed 1-year PFS estimate trended higher than the historical estimate, a target PFS of 81% was pre-specified as warranting further investigation. Significant toxicities were associated with the addition of bevacizumab, including an increased incidence of cardiac dysfunction and GI perforation. Our results do not support additional studies of this regimen in this patient population. Disclosures: Stopeck: Genentech: Consultancy, Honoraria, Speakers Bureau. Off Label Use: Bevacizumab therapy in NHL. Fisher:Roche: Consultancy.

Risk Factors for the Development of and Outcomes of Patients Who Develop Severe Cytokine Release Syndrome after Peripheral Blood Haploidentical Donor Transplant

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3419-3419
Author(s):  
Ramzi Abboud ◽  
Michael Slade ◽  
Wenners Ballard ◽  
Jesse Keller ◽  
John F DiPersio ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Patient Characteristics ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Graft Versus Host ◽  
Grade 3 ◽  
Active Disease ◽  
Related Mortality

Abstract Background:Allogeneic hematopoietic cell transplantation is a cornerstone of therapy for hematologic malignancies and often a patient's only curative intent treatment. Following development of post-transplant cyclophosphamide (PTCy) regimens, the use of haploidentical hematopoietic cell transplantation (haplo-HCT) has expanded. While overall outcomes for haploidentical transplantation appear to be excellent, its novel approach brings toxicities that are particular to its biological and clinical milieu. We recently described occurrence of severe cytokine release syndrome (CRS) after haplo-HCT. We further reported that severe CRS was associated with poor clinical outcomes, including transplant related mortality (TRM), overall survival (OS), and neutrophil engraftment (Abboud et al, BBMT, 2016). However, the factors predicting the occurrence of and long-term outcomes of patients who develop severe CRS after haplo-HCT is currently not known. Objective: To describe our clinical experience with CRS in an expanded cohort of haplo-HCT patients, its implication on clinical outcomes and elucidation of possible risk factors for the development of severe CRS. Patients and Methods: We performed a retrospective review of patients who had undergone peripheral blood T-Cell replete haplo-HCT with PTCy from July 2009 through March 2016 at our institution. A total of 137 patients were identified, 51% (74) were male, with a median age at transplant of 52 (19-73), a total of 40% (57) had active disease at the time of transplant. The most common diagnosis was AML (93 pts), followed by ALL (16 pts) and MDS (15 pts). Thirty-one percent (44 pts) had undergone prior transplant. In grading CRS, we used our approach modified from by Lee et al (Blood, 2014). Twenty-two patient, donor and disease characteristics were examined to identify predictors for the development of severe CRS. Results:One hundred and twenty-four (90%) of patients met criteria for CRS, and 26 (19%) suffered from severe (grade 3-4) CRS. Virtually all patients (99%) with CRS suffered from fevers. Patients with severe CRS had a significant delay in neutrophil (p < 0.0001) and platelet (p < 0.0001) engraftment compared to the patients who developed mild or no CRS (Figure 1A and 1B). Severe CRS was also associated with a high early transplant related mortality; the rate of death before post-transplant day 28 was 6.9 times higher for patients with grade 3-4 CRS compared with those with mild CRS (p < 0.0001, Figure 1C). Consistent with these findings, the development of severe CRS was associated with extremely poor survival. Median survival was 3 months for grade 3-4 CRS, 15 months for grade 1-2 CRS, and 13 months for no CRS. One-year OS was 4% for grade 3-4 CRS, 55% for grade 1-2 CRS, and 50% for no CRS (Figure 1D). There was no difference in the cumulative incidence of relapse, acute graft versus host disease, and chronic graft versus host disease (data not shown). A total of nine patients received Anti-IL-6 Therapy with tociluzimab (4 mg/kg of actual body weight), 4 of which suffered from severe CRS. In terms of predictive factors, the development of severe CRS was associated with disease risk index (p=0.037), HCT-CI score (p=0.005) and presence of a previous transplant (p=0.026) by univariate analysis. Risk and severity of CRS did not differ by age, ABO mismatch, age, CMV status of donor, donor sex, T-cell or CD34 cell dose. There was no difference in rates of CRS among patients in remission or with active disease at the time of transplant. Conclusions: Severe CRS after peripheral blood haplo-HCT is associated with high early TRM, poor OS and delayed neutrophil and platelet engraftment. Furthermore, patients with high DRI, high HCT-CI and prior HCT are at a higher risk for the development of severe CRS after haplo-HCT. We have previously shown the safety and potential efficacy of using anti-IL-6 therapy in these patients. Our current results suggest potential benefit to targeting this pathway prophylactically in patients at high risk for the development of severe CRS. Table Patient Characteristics Table. Patient Characteristics Figure CRS impacts neutrophil (A) and platelet (B) engraftment and is associated with high TRM (C) and poor OS (D). Figure. CRS impacts neutrophil (A) and platelet (B) engraftment and is associated with high TRM (C) and poor OS (D). Disclosures DiPersio: Incyte Corporation: Research Funding. Abboud:Gerson and Lehman Group: Consultancy; Merck: Research Funding; Teva: Research Funding, Speakers Bureau; Novartis: Research Funding; Pfizer: Research Funding; Seattle Genetics: Research Funding; Alexion: Honoraria; Baxalta: Honoraria; Pharmacyclics: Honoraria; Takeda: Honoraria; Cardinal: Honoraria. Fehniger:Affimed: Consultancy; Celgene: Research Funding; Fortress Biotech: Consultancy.

Prophylactic treatment of irinotecan-induced diarrhea with neomycin (a randomized, placebo-controlled, double-blind study)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3626-3626
Author(s):  
R. H. Mathijssen ◽  
F. A. De Jong ◽  
D. F. Kehrer ◽  
R. H. Van Schaik ◽  
J. Verweij ◽  
...  
Keyword(s):  
Prophylactic Treatment ◽  
Plasma Concentrations ◽  
Aminoglycoside Antibiotic ◽  
Concomitant Administration ◽  
Patient Characteristics ◽  
Common Side Effect ◽  
Double Blind Study ◽  
Double Blind ◽  
Severe Diarrhea ◽  
Grade 3

3626 Background: Delayed-type diarrhea is a common side-effect of irinotecan, and is associated with a bacterial-mediated formation of the active irinotecan metabolite SN-38 from its glucuronide conjugate in the intestines. We hypothesized that concomitant administration of the aminoglycoside antibiotic neomycin would diminish exposure of the gut to SN-38, ameliorating the incidence of diarrhea. Methods: Patients were treated with irinotecan in a randomized, placebo-controlled, double-blind trial. In arm A, patients received irinotecan (350 mg/m2 i.v. for 90 minutes once every 3 weeks) combined with neomycin (660 mg orally 3 times daily for 3 consecutive days, starting 2 days before chemotherapy). In arm B, patients received the same irinotecan regimen with placebo. To detect a 50% reduction to less than grade 2 diarrhea (power=.80; P=.05), 60 patients had to be studied. Blood samples for additional pharmacokinetic and pharmacogenetic analyses were obtained after separate informed consent. Results: Sixty-two patients were evaluable for toxicity analysis. Relevant baseline patient characteristics (P>.06), SN-38 plasma concentrations (P=.80; N=43), and UGT1A1*28 genotype status (P=.58; N=52) were similar in both arms. Distribution, severity, and duration of diarrhea did not differ significantly between both arms (P>.32), although grade 3 diarrhea tended to be less frequent in the neomycin arm (45% reduction; P=.19). Grade 2 nausea was more common in this arm (39% vs. 9%; P<.01). The presence of at least one UGT1A1*28 allele was strongly related to the incidence of grade 2–3 diarrhea (69% vs. 34%; P=.01). Conclusions: Our results do not suggest a role for neomycin in the prophylactic treatment of irinotecan-induced diarrhea. In addition, neomycin does not influence systemic SN-38 pharmacokinetics. Also, it is suggested that each patient’s UGT1A1*28 genotype status could be used as a prospective screening tool to prevent severe diarrhea. No significant financial relationships to disclose.

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