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.

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.

Primary prophylactic granulocyte colony-stimulating factor (GCSF) in Gilbert’s disease patients treated with FOLFIRI first line for metastatic colorectal cancer (mCRC): Final results of the FFCD 0604 study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3614-3614 ◽  
Author(s):  
Thierry Lecomte ◽  
Olivier Bouche ◽  
Alice oden-Gangloff ◽  
Karine Le Malicot ◽  
Thomas Aparicio ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Hepatic Metastases ◽  
Progression Free Survival ◽  
Primary Site ◽  
High Rate ◽  
Molecular Technique ◽  
Best Response ◽  
Life Threatening ◽  
Grade 3

3614 Background: Gilbert’s disease patients (pts) (homozygotous for the UGT1A1*28 allele) have a major risk (>30%) of severe, life-threatening, neutropenia when treated with Irinotecan (IRI). The aim of this study was to demonstrate that, in these pts, treated with IRI 1st line for mCRC, primary prevention with GCSF (lenograstim) reduces under 10% the risk of grade 4 or febrile neutropenia. Methods: This is a prospective, multicenter, phase II study of FOLFIRI + bevacizumab 1st line (IRI 180 mg/m² every 2 weeks) and primary prophylactic GCSF (D5 to D11 each course) in mCRC pts with Gilbert’s disease. Pre-chemotherapy UGT1A1 genotyping was centralized and standardized using a biological molecular technique applied on DNA blood-extracted lymphocytes. Using a 2-step Fleming design, (α=5% and β=90%), 30 pts had to be included with an interim analysis (IA) planned after 20 pts and 4 months of follow-up. Results: Twenty pts from 7 centers were included between 10/2007 and 02/2012 and 19 analysed for the IA. Median pts age was 63 years (range: 45-73), 60% were females, 90% were PS 0 or 1, 80% had a colic primary site and 73% hepatic metastases. The primary site was non- resected in 1/3 of pts. The total number of administered courses of chemotherapy was 229 with a median of 12 per pt (range: 1-40). Among all these courses, 213 were administered with GCSF. IRI was administered as defined by the protocol with a nearly 100% rate of received /theoretical dose. Grade 3 neutropenia rate was 10.5%. No grade 3-4 diarrhea, no grade 4 or febrile neutropenia and no toxic death were observed. No declared SAEs were related to GCSF. In term of best response at 6 months, 7 pts were in complete or partial response and 9 had stable disease. Median progression free survival and overall survival were respectively 8.7 months (4.9; 13.4) and 24.4 months (12.6; ND). Conclusions: This study is the first to demonstrate that a pharmacogenetic approach based on a simple genetic test easy to perform can achieve a high rate of safe and performant administration of IRI in high risk mCRC pts. Clinical trial information: NCT00541125.

Lifetime traumas and their influence on advanced cancer patients’ illness understanding and likelihood of end-of-life discussions.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9146-9146
Author(s):  
Elizabeth L Kacel ◽  
Paul K Maciejewski ◽  
Holly Gwen Prigerson
Keyword(s):  
Logistic Regression ◽  
Posttraumatic Stress ◽  
End Of Life ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Patient Characteristics ◽  
Advanced Cancer Patients ◽  
Life Threatening ◽  
Oncology Providers ◽  
The Impact

9146 Background: Research on posttraumatic stress in cancer patients has focused on patient reactions to their cancer diagnosis. Few studies have examined the impact of lifetime traumatic events prior to diagnosis on how advanced cancer patients understand the life-threatening nature of their illness and how likely they are to discuss their end-of-life (EOL) wishes with their oncology providers. Methods: The Coping with Cancer (CwC) is an NCI-funded prospective, multi-institutional cohort study of advanced cancer patients and their caregivers. Participants were recruited from September 2002 to February 2008 from six comprehensive cancer centers across the United States. Lifetime traumas were captured by the number of events reported in response to the Structured Clinical Interview for the DSM-IV (SCID) Lifetime Posttraumatic Stress Disorder question that probed for “extremely upsetting” life events. Associations between patient characteristics and number of lifetime traumas were estimated as odds ratios using ordinal logistic regression. Associations between number of lifetime traumatic exposures, controlling for confounding patient characteristics, and patient Terminal Illness Acknowledgement (TIA) and reports of EOL discussions were estimated as odds ratios using multiple logistic regression. Results: After adjusting for race, education, and recruitment site, the number of lifetime traumas patients reported remained significantly associated with TIA (OR = 1.25, p = .034) and discussion of EOL wishes (OR = 1.29, p = .013). Conclusions: The greater the number of traumatic experiences reported by cancer patients the more likely they are to acknowledge that they are terminally ill and discuss their end-of-life wishes with their oncology providers. The impact of witnessing or experiencing serious or life-threatening events in the past appears to improve advanced cancer patients’ abilities to understand the seriousness of their condition and increases the likelihood that they will discuss their preferences for care at the end of life with their doctors.

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.

scholarly journals Early fatigue in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: an insight from clinical practice

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Alessio Cortellini ◽  
Maria G. Vitale ◽  
Federica De Galitiis ◽  
Francesca R. Di Pietro ◽  
Rossana Berardi ◽  
...  
Keyword(s):  
Adverse Event ◽  
Clinical Practice ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Common Grade ◽  
Study Population ◽  
Grade 3 ◽  
Ecog Ps

Abstract Background Fatigue was reported as the most common any-grade adverse event (18.3%), and the most common grade 3 or higher immune-related adverse event (irAE) (0.89%) in patients receiving PD-1/PD-L1 checkpoint inhibitors in clinical trial. Methods The aim of this retrospective multicenter study was to evaluate the correlations between “early ir-fatigue”, “delayed ir-fatigue”, and clinical outcomes in cancer patients receiving PD-1/PD-L1 inhibitors in clinical practice. Results 517 patients were evaluated. After the 12-weeks landmark selection, 386 (74.7%) patients were eligible for the clinical outcomes analysis. 40.4% were NSCLC, 42.2% were melanoma, 15.3% renal cell carcinoma and 2.1% other malignancies. 76 patients (19.7%) experienced early ir-fatigue (within 1 month from treatment commencement), while 150 patients (38.9%) experienced delayed ir-fatigue. Early ir-fatigue was significantly related to shortened PFS (HR = 2.29 [95% CI 1.62–3.22], p < 0.0001) and OS (HR = 2.32 [95% CI 1.59–3.38], p < 0.0001) at the multivariate analysis. On the other hand, we found a significant association between the occurrence of early ir-fatigue, ECOG-PS ≥ 2 (p < 0.0001), and disease burden (p = 0.0003). Delayed ir-fatigue was not significantly related to PFS nor OS. Conclusions Early ir-fatigue seems to be negative prognostic parameter, but to proper weight its role we must to consider the predominant role of performance status, which was related to early ir-fatigue in the study population.

scholarly journals Tolerance of weekly metronomic paclitaxel and carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer patients who are unlikely to tolerate 3 weekly paclitaxel and carboplatin

2016 ◽  
Vol 05 (02) ◽  
pp. 063-066 ◽  
Author(s):  
S. B. Dessai ◽  
S. Chakraborty ◽  
T. V.S. Babu ◽  
S. Nayanar ◽  
A. Bhattacharjee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Response Rates ◽  
Weekly Paclitaxel ◽  
Life Threatening ◽  
Radiological Response ◽  
Grade 3

Abstract Objective: There are little data regarding safety and effectiveness of neoadjuvant chemotherapy (NACT) in patients who are considered unfit for receiving 3 weekly paclitaxel and carboplatin. The aim of this study was to examine the toxicity and response rates of weekly paclitaxel and carboplatin as NACT in such cohort of patients. Methods: Study population included advanced ovarian cancer patients who were unlikely to tolerate 3 weekly paclitaxel and carboplatin and hence received weekly paclitaxel (80 mg/m 2) and carboplatin AUC-2 as NACT. The data regarding the baseline characteristics, chemotherapy tolerance, completion rates, toxicity (Common Terminology Criteria for Adverse Events version 4.02), and radiological response rates are presented. SPSS version 16 was used for analysis. Descriptive statistics is presented. Results: Eleven patients received this schedule. Nine patients completed nine cycles of NACT. Except one, all patients completed NACT with an average relative dose intensity of >0.8. There was no chemotherapy-related mortality. Grade 3-4 life-threatening complications were seen in two patients. The post NACT response rate was 100%. Conclusions: Weekly paclitaxel and carboplatin chemotherapy is safe and efficacious in patients who are unsuitable for 3 weekly paclitaxel and carboplatin chemotherapy schedules.

Effect of Undertriage on the Outcomes of Cancer Patients with Febrile Neutropenia, Sepsis, and Septic Shock

2021 ◽  
pp. 105477382199968
Author(s):  
Anas Alsharawneh
Keyword(s):  
Emergency Department ◽  
Septic Shock ◽  
Length Of Stay ◽  
Febrile Neutropenia ◽  
Cancer Patients ◽  
Emergency Setting ◽  
Extended Length ◽  
Life Threatening ◽  
Sepsis And Septic Shock ◽  
Timely Treatment

Sepsis and neutropenia are considered the primary life-threatening complications of cancer treatment and are the leading cause of hospitalization and death. The objective was to study whether patients with neutropenia, sepsis, and septic shock were identified appropriately at triage and receive timely treatment within the emergency setting. Also, we investigated the effect of undertriage on key treatment outcomes. We conducted a retrospective analysis of all accessible records of admitted adult cancer patients with febrile neutropenia, sepsis, and septic shock. Our results identified that the majority of patients were inappropriately triaged to less urgent triage categories. Patients’ undertriage significantly prolonged multiple emergency timeliness indicators and extended length of stay within the emergency department and hospital. These effects suggest that triage implementation must be objective, consistent, and accurate because of the several influences of the assigned triage scoring on treatment and health outcomes.

scholarly journals Cost-effectiveness of paclitaxel, doxorubicin, cyclophosphamide and trastuzumab versus docetaxel, cisplatin and trastuzumab in new adjuvant therapy of breast cancer in china

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiaoping Xu ◽  
Li Yuanyuan ◽  
Zhu Jiejing ◽  
Liu Jian ◽  
Li Qingyu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Partial Response ◽  
Cancer Patients ◽  
Transition Probabilities ◽  
Complete Response ◽  
Sensitivity Analyses ◽  
Half Cycle ◽  
Breast Cancer Patients ◽  
Grade 3

Abstract Background Breast cancer is the most common cancer among women in China. Amplification of the Human epidermal growth factor receptor type 2 (HER2) gene is present and overexpressed in 18–20% of breast cancers and historically has been associated with inferior disease-related outcomes. There has been increasing interest in de-escalation of therapy for low-risk disease. This study analyzes the cost-effectiveness of Doxorubicin/ Cyclophosphamide/ Paclitaxel/ Trastuzumab (AC-TH) and Docetaxel/Carboplatin/Trastuzumab(TCH) from payer perspective over a 5 year time horizon. Methods A half-cycle corrected Markov model was built to simulate the process of breast cancer events and death occurred in both AC-TH and TCH armed patients. Cost data came from studies based on a Chinese hospital. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed.The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted. Results We identified 41 breast cancer patients at Hangzhou First People’s Hospital, among whom 15 (60%) had a partial response for AC-TH treatment and 13 (81.25%) had a partial response for TCH treatment.No cardiac toxicity was observed. Hematologic grade 3 or 4 toxicities were observed in 1 of 28 patients.Nonhematologic grade 3 or 4 toxicities with a reverse pattern were observed in 6 of 29 patients. The mean QALY gain per patient compared with TCH was 0.25 with AC-TH, while the incremental costs were $US13,142. The incremental cost-effectiveness ratio (ICER) of AC-TH versus TCH was $US 52,565 per QALY gained. Conclusions This study concluded that TCH neoadjuvant chemotherapy was feasible and active in HER2-overexpressing breast cancer patients in terms of the pathological complete response, complete response, and partial response rates and manageable toxicities.

ECG-guided PICC insertion using a new silicon catheter with a conductive tip: A retrospective clinical study

2021 ◽  
pp. 112972982110025
Author(s):  
Yu-Xia Yin ◽  
Wei Gao ◽  
Sheng-Yu Feng ◽  
Deng-Xu Wang ◽  
Min Wan ◽  
...  
Keyword(s):  
Clinical Study ◽  
Daily Practice ◽  
Patient Characteristics ◽  
Mobile App ◽  
High Rate ◽  
Exit Site Infection ◽  
Increased Risk ◽  
Retrospective Clinical Study ◽  
Operation Rate ◽  
Catheter Tip

Objective: Safety and efficacy of ECG-guided PICC insertion using a new silicon catheter with a conductive tip was evaluated in daily practice. Methods: A retrospective study was conducted on 1659 patients who accepted successful tip-conductive PICC placement and clinically followed-up until the catheter removal between January 2018 and April 2019. Baseline of patient characteristics, catheter placement characteristics, date of dressing changes as well as records of catheter-related complications were extracted from a special designed mobile APP. Results: The first-attempt success (success of placing catheter tip to the ideal position by primary indwelling operation) rate of PICC placement was 99.3%. The average duration of PICC placement was 128.7 ± 39.5 days and 1535 patients (92.5%) reached the therapy end-point without any complications and removed the catheter normally. The cumulative rates of total complications were 7.5%, including exit site infection (2.5%), phlebitis (0.9%), DVT (1.0%), catheter malposition (1.1%), catheter breakage (0.1%), and liquid extravasation (1.8%). In multivariable logistic regression analyses, hyperlipidemia, diabetes mellitus, lung cancer, stomach cancer, and lymphoma were significantly associated with increased risk of complications, as the independent risk factors. Conclusions: This retrospective clinical study demonstrates that ECG-guided insertion of a new tip-conductive PICC is associated with a high rate of first-attempt success and low rate of catheter related complications.

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