Dose: Intensity, Response

Author(s):  
Nicole Brandt
Author(s):  
C. Renn Upchurch Sweeney ◽  
J. Rick Turner ◽  
J. Rick Turner ◽  
Chad Barrett ◽  
Ana Victoria Soto ◽  
...  

2020 ◽  
Vol 12 ◽  
pp. 175883592097411
Author(s):  
Natalie Reizine ◽  
Everett E. Vokes ◽  
Ping Liu ◽  
Tien M. Truong ◽  
Rita Nanda ◽  
...  

Background: Many cancer patients who receive chemotherapy experience adverse drug effects. Pharmacogenomics (PGx) has promise to personalize chemotherapy drug dosing to maximize efficacy and safety. Fluoropyrimidines and irinotecan have well-known germline PGx associations. At our institution, we have delivered PGx clinical decision support (CDS) based on preemptively obtained genotyping results for a large number of non-oncology medications since 2012, but have not previously evaluated the utility of this strategy for patients initiating anti-cancer regimens. We hypothesize that providing oncologists with preemptive germline PGx information along with CDS will enable individualized dosing decisions and result in improved patient outcomes. Methods: Patients with oncologic malignancies for whom fluoropyrimidine and/or irinotecan-inclusive therapy is being planned will be enrolled and randomly assigned to PGx and control arms. Patients will be genotyped in a clinical laboratory across panels that include actionable variants in UGT1A1 and DPYD. For PGx arm patients, treating providers will be given access to the patient-specific PGx results with CDS prior to treatment initiation. In the control arm, genotyping will be deferred, and dosing will occur as per usual care. Co-primary endpoints are dose intensity deviation rate (the proportion of patients receiving dose modifications during the first treatment cycle), and grade ⩾3 treatment-related toxicities throughout the treatment course. Additional study endpoints will include cumulative drug dose intensity, progression-free survival, dosing of additional PGx supportive medications, and patient-reported quality of life and understanding of PGx. Discussion: Providing a platform of integrated germline PGx information may promote personalized chemotherapy dosing decisions and establish a new model of care to optimize oncology treatment planning.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Spyridoula Vazou ◽  
Collin A. Webster ◽  
Gregory Stewart ◽  
Priscila Candal ◽  
Cate A. Egan ◽  
...  

Abstract Background/Objective Movement integration (MI) involves infusing physical activity into normal classroom time. A wide range of MI interventions have succeeded in increasing children’s participation in physical activity. However, no previous research has attempted to unpack the various MI intervention approaches. Therefore, this study aimed to systematically review, qualitatively analyze, and develop a typology of MI interventions conducted in primary/elementary school settings. Subjects/Methods Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to identify published MI interventions. Irrelevant records were removed first by title, then by abstract, and finally by full texts of articles, resulting in 72 studies being retained for qualitative analysis. A deductive approach, using previous MI research as an a priori analytic framework, alongside inductive techniques were used to analyze the data. Results Four types of MI interventions were identified and labeled based on their design: student-driven, teacher-driven, researcher-teacher collaboration, and researcher-driven. Each type was further refined based on the MI strategies (movement breaks, active lessons, other: opening activity, transitions, reward, awareness), the level of intrapersonal and institutional support (training, resources), and the delivery (dose, intensity, type, fidelity). Nearly half of the interventions were researcher-driven, which may undermine the sustainability of MI as a routine practice by teachers in schools. An imbalance is evident on the MI strategies, with transitions, opening and awareness activities, and rewards being limitedly studied. Delivery should be further examined with a strong focus on reporting fidelity. Conclusions There are distinct approaches that are most often employed to promote the use of MI and these approaches may often lack a minimum standard for reporting MI intervention details. This typology may be useful to effectively translate the evidence into practice in real-life settings to better understand and study MI interventions.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guohua Liang ◽  
Wenjie Ma ◽  
Yanfang Zhao ◽  
Eryu Liu ◽  
Xiaoyu Shan ◽  
...  

Abstract Background Hand-foot syndrome (HFS) is a side effect of skin related to pegylated liposomal doxorubicin (PLD) application. Moderate to severe hand-foot syndrome (MSHFS) might have a serious impact on patients’ quality of life and treatment. However, information on risk factors for the development of MSHFS is still limited. To analyze the risk factors for PLD-induced MSHFS in breast cancer patients and constructed a logistic regression prediction model. Methods We conducted a retrospective analysis of breast cancer patients who were treated with a PLD regimen in the Tumor Hospital of Harbin Medical University from January 2017 to August 2019. A total of 26 factors were collected from electronic medical records. Patients were divided into MSHFS (HFS > grade 1) and NMHFS (HFS ≤ grade 1) groups according to the NCI classification. Statistical analysis of these factors and the construction of a logistic regression prediction model based on risk factors. Results A total of 44.7% (206/461) of patients developed MSHFS. The BMI, dose intensity, and baseline Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels in the MSHFS group, as well as good peripheral blood circulation, excessive sweat excretion, history of gallstones, and tumour- and HER2-positive percentages, were all higher than those in the NMHFS group (P < 0.05). The model for predicting the occurrence of MSHFS was P = 1/1 + exp. (11.138–0.110*BMI-0.234*dose intensity-0.018*baseline ALT+ 0.025*baseline AST-1.225*gallstone history-0.681* peripheral blood circulation-1.073*sweat excretion-0.364*with or without tumor-0.680*HER-2). The accuracy of the model was 72.5%, AUC = 0.791, and Hosmer-Lemeshow fit test P = 0.114 > 0.05. Conclusions Nearly half of the patients developed MSHFS. The constructed prediction model may be valuable for predicting the occurrence of MSHFS in patients.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick B. Johnston ◽  
Amanda F. Cashen ◽  
Petros G. Nikolinakos ◽  
Anne W. Beaven ◽  
Stefan Klaus Barta ◽  
...  

Abstract Background Belinostat is a histone deacetylase inhibitor approved for relapsed refractory peripheral T-cell lymphoma (PTCL). The primary objective of this study was to determine the maximum tolerated dose (MTD) of belinostat combined with CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall response rate (ORR), and belinostat pharmacokinetics (PK). Methods Patients were ≥ 18 years with histologically confirmed, previously untreated PTCL. Patients received belinostat (1000 mg/m2 once daily) + standard CHOP for 6 cycles with varying schedules using a 3 + 3 design in Part A. Part B enrolled patients at MTD dose. Results Twenty-three patients were treated. One patient experienced DLT (Grade 3 non-hematologic toxicity) on Day 1–3 schedule, resulting in escalation to Day 1–5 schedule (n = 3). No DLTs were observed and Day 1–5 schedule with 1000 mg/m2 was declared as MTD. Twelve additional patients were enrolled in Part B using MTD. Median relative dose intensity was 98%. All patients experienced adverse events (AEs), including nausea (78%), fatigue (61%), and vomiting (57%). Serious AEs occurred in 43%, with febrile neutropenia (17%) and pyrexia (13%). Overall ORR was 86% with 71% reported CR at MTD. Belinostat PK parameters were similar to single-agent. Conclusions Bel-CHOP was well tolerated and MTD in CHOP combination was the same dose and schedule as single agent dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT01839097.


Author(s):  
Kenichi Matsumoto ◽  
Akihiko Miyamoto ◽  
Tomoya Kawase ◽  
Taro Murai ◽  
Yuta Shibamoto

Abstract Aim: To evaluate the efficacy of concurrent chemotherapy and high-dose (≥55 Gy) intensity-modulated radiotherapy (CCIMRT) in comparison with chemotherapy alone and intensity-modulated radiotherapy (IMRT) alone for unresectable locally advanced or metastatic pancreatic cancer. Methods: Forty-six patients with pancreatic cancer undergoing CCIMRT (n = 17), chemotherapy alone (n = 16) or IMRT alone (n = 13) were analysed. Overall survival (OS), locoregional progression-free survival (LRPFS) and gastrointestinal toxicities were evaluated. The median radiation dose was 60 Gy (range, 55–60) delivered in a median of 25 fractions (range, 24–30). Gemcitabine (GEM) alone, GEM + S-1, S-1 alone, FOLFIRINOX and GEM + nab-paclitaxel were used in CCIMRT and chemo-monotherapy. Results: The 1-year OS rate was 69% in the CCIMRT group, 27% in the chemotherapy group and 38% in the IMRT group (p = 0·12). The 1-year LRPFS rate was 73, 0 and 40% in the 3 groups, respectively (p = 0·012). Acute Grade ≥ 2 gastrointestinal toxicity (nausea, diarrhea) was observed in 12% (2/17) in the CCIMRT group, 25% (4/16) in the chemotherapy group and 7·7% (1/13) in the IMRT group (p = 0·38). Late Grade 3 gastrointestinal bleeding was observed in 6·3% (1/16) in the chemotherapy group. Conclusion: High-dose CCIMRT yielded acceptable toxicity and favorable OS and LRPFS.


Author(s):  
Faheem Khan ◽  
Fatma Gargoum ◽  
Barry Kennedy ◽  
JIM CLAIR ◽  
Bernie O'Connor ◽  
...  

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