Browsing by Author "Wood, William A."

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    A phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer
    (Oxford University Press, 2024) Sanoff, Hanna K.; Deal, Allison M.; Patel, Jai; Sorah, Jonathan D.; Gaddy, Jacquelyne; O’Neil, Bert; Turk, Anita; Irvin, William; Boles, Jeremiah; Lee, Michael S.; McRee, Autumn; Wardell, Alexis C.; Weck, Karen E.; Basch, Ethan; Wood, William A.; Innocenti, Federico; Medicine, School of Medicine
    Background: FOLFIRI is a standard regimen for metastatic colorectal cancer (mCRC). We hypothesized that a pharmacogenomic-directed strategy where more efficient irinotecan metabolizers (UGT1A1 *1/*1 homozygotes and *1/*28 heterozygotes) receive higher-than-standard irinotecan doses would improve progression-free survival (PFS) compared to non-genotype selected historical controls with acceptable toxicity. Methods: In this phase II multicenter study irinotecan dosing in first-line FOLFIRI and bevacizumab for mCRC was based on UGT1A1 genotype with *1/*1, *1/*28, and *28/*28 patients receiving 310 mg/m2, 260 mg/m2, and 180 mg/m2, respectively. Primary endpoint was PFS. Secondary endpoints were investigator and patient-reported adverse events, and estimation of overall survival (OS). Results: One-hundred patients were enrolled with 91 evaluable for PFS and 83 evaluable for best response. Median PFS was 12.5 months (90% CI 10.9, 15.4), shorter than the anticipated alternative hypothesis of 14 months. PFS by genotype was 12.5 months (90% CI 10.9, 17.4) for *1/*1, 14.6 months (90% CI 11.8, 17.5) for *1/*28, and 6 months (90% CI 2.3, 7.7) for *28/28, respectively. OS was 24.5 months (90% CI 19.1, 30.7) and by genotype was 26.5 (90% CI 19.1, 32.9), 25.9 (90% CI 17.6, 37.7), and 13.4 (90% CI 2.3, 20.5) months for *1/*1, *1/*28, and *28/*28, respectively. G3/4 toxicity was similar between all subgroups, including diarrhea and neutropenia. Conclusions: A pharmacogenomic-directed irinotecan strategy improved PFS in the *1/*1 and *1/*28 genotypes with higher rates of neutropenia and similar rates of diarrhea compared to expected with standard FOLFIRI dosing. However, improvements in response rate and PFS were modest. This strategy should not change standard practice for mCRC patients in the first-line setting.
  • Thumbnail Image
    Item
    A randomized double-blind placebo-controlled trial of intravenous thiamine for prevention of delirium following allogeneic hematopoietic stem cell transplantation
    (Elsevier, 2021) Nakamura, Zev M.; Deal, Allison M.; Park, Eliza M.; Quillen, Laura J.; Chien, Stephanie A.; Stanton, Kate E.; McCabe, Sean D.; Heiling, Hillary M.; Wood, William A.; Shea, Thomas C.; Rosenstein, Donald L.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Objective: To determine if high dose intravenous (IV) thiamine can prevent delirium during hospitalization following allogeneic HSCT. Secondarily, we evaluated the effects of high dose IV thiamine on thiamine levels and explored risk factors for delirium. Methods: Randomized, double-blind, placebo-controlled trial in patients undergoing allogeneic HSCT at a U.S. academic medical center between October 2017 and March 2020. 64 participants were randomized 1:1 to thiamine 200 mg IV three times daily for 7 days or placebo. We used the Delirium Rating Scale to assess for delirium. Delirium incidence was compared between groups using the chi-square test. Group differences in time to onset and duration of delirium were compared using the Kaplan-Meier method. Fisher's Exact and Wilcoxon Rank Sum tests were used to examine associations between pre-transplantation variables and delirium. Results: 61 participants were analyzed. Delirium incidence (25% vs. 21%, Chi-square (df = 1) = 0.12, p = 0.73), time to onset, duration, and severity were not different between study arms. Immediately following the intervention, thiamine levels were higher in the thiamine arm (275 vs. 73 nmol/L, t-test (df = 57) = 13.63, p < 0.0001), but not predictive of delirium. Variables associated with delirium in our sample included disease severity, corticosteroid exposure, infection, and pre-transplantation markers of nutrition. Conclusion: High dose IV thiamine did not prevent delirium in patients receiving allogeneic HSCT. Given the multiple contributors to delirium in this population, further research regarding the efficacy of multicomponent interventions may be needed.
  • Thumbnail Image
    Item
    Breaking the Age Barrier: Physicians' Perceptions of Candidacy for Allogeneic Hematopoietic Cell Transplantation in Older Adults
    (Elsevier, 2021) Mishra, Asmita; Preussler, Jaime M.; Bhatt, Vijaya Raj; Bredeson, Christopher; Chhabra, Saurabh; D'Souza, Anita; Dahi, Parastoo B.; Danaher Hacker, Eileen; Gowda, Lohith; Hashmi, Shahrukh K.; Howard, Dianna S.; Jakubowski, Ann; Jayani, Reena; Koll, Thuy; Olin, Rebecca L.; Popat, Uday R.; Rodriguez, Cesar; Rosko, Ashley; Sabloff, Mitchell; Sorror, Mohamed L.; Sung, Anthony D.; Ustun, Celalettin; Wood, William A.; Burns, Linda; Artz, Andrew; School of Nursing
    Background: Despite continued increases in use of allogeneic hematopoietic cell transplantation (alloHCT) among older adults, no standardized geriatric assessment (GA) has been established to risk-stratify for transplant-related morbidity. We conducted a survey of transplant physicians to determine perceptions of the impact of older age (≥60 years) on alloHCT candidacy, and utilization of tools to gauge candidacy. Methods: We conducted a 23-item, online cross-sectional survey of HCT physicians caring for adults in the United States between May and July 2019. Results: Of the 770 invited HCT physicians, 175 (22.7%) completed the survey. The majority of respondents were 41–60 years old, male, and practiced in a higher volume teaching hospital. When considering regimen intensity, 29 physicians (17%) stated they would consider a myeloablative regimen for patients ≥70 years, and 141 (82%) would consider reduced intensity/non-myeloablative conditioning for patients ≥70 years. Almost all (90%) endorsed the need for a specialized assessment of pre-HCT vulnerabilities to guide candidacy decisions for older adults. Most physicians reported their centers rarely (33%) or never (46%) utilize a dedicated geriatrician/geriatric-oncologist to assess alloHCT candidates ≥60 years. Common barriers to performing a GA included uncertainty about which tools to use, lack of knowledge and training, and lack of appropriate clinical support staff. Conclusions: Many alloHCT physicians will consider alloHCT in patients up to age 75 years and not uncommonly, in patients older than that. However, application of tools and domains varies widely to assess candidacy in older adults. Incorporation of a standardized pre-transplant health assessment tool for risk stratification is a significant unmet need.
  • Thumbnail Image
    Item
    Collaborative Care for Depression and Anxiety in the Bone Marrow Transplant Population: A Pilot Feasibility Study
    (Wiley, 2021) Copeland, Anureet C.; Tan, Xianming; Nash, Rebekah P.; Holmes, Emily G.; Markey, Janell; Shea, Thomas C.; Wood, William A.; Park, Eliza M.; Psychology, School of Science
  • Thumbnail Image
    Item
    Longitudinal patient-reported outcomes on genotype-guided irinotecan dosing: feasibility and clinical relevance
    (Oxford University Press, 2024) Sorah, Jonathan D.; Deal, Allison M.; Stein, Sophia I.; Jonsson, Mattias; Innocenti, Federico; Turk, Anita; Boles, Jeremiah C.; Irvin, William; Basch, Ethan M.; Sanoff, Hanna K.; Wood, William A.; Medicine, School of Medicine
    Introduction: Standard investigator-based adverse events (AE) assessment is via CTCAE for clinical trials. However, including the patient perspective through PRO (patient-reported outcomes) enhances clinicians' understanding of patient toxicity and fosters early detection of AEs. We assessed longitudinal integration of PRO-CTCAE within clinical workflow in a phase II trial. Materials and methods: As a sub-study in a phase II trial of genotype-directed irinotecan dosing evaluating efficacy in patients with metastatic colorectal cancer receiving FOLFIRI and bevacizumab, patients reported on 13 AEs generating a PRO-CTCAE form. The primary objective was to estimate forms completed by patients and clinicians at least 80% of time. Secondary objectives were estimating concordance and time to first score of specific symptoms between patient and clinician pairs. Results: Feasibility of longitudinal PRO-CTCAE integration was met as 96% of patients and clinician-patient pairs completed at least 80% of PRO-CTCAE forms available to them with 79% achieving 100% completion. Concordance between patient and clinician reporting a severe symptom was 73% with 24 disconcordant pairs, 21 involved patients who reported a severe symptom that the clinician did not. Although protocol-mandated dose reductions were guided by CTCAE not PRO-CTCAE responses, the median time to dose reduction of 2.53 months, and the time-to-event curve closely approximated time to patient-reported toxicity. Conclusion: Longitudinal integration of PRO-CTCAE paired CTCAE proved feasible. Compared to clinicians, patients reported severe symptoms more frequently and earlier. Patient-reported toxicity more closely aligned with dose decreases indicating incorporation into routine clinical practice may enhance early detection of toxicity improving patient safety and quality of life.