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Current Oncology (Toronto, Ont.) Sep 2021From a Canadian perspective, there has been a limited discussion on the frontline management of young, fit patients with chronic lymphocytic leukemia (CLL). The... (Review)
Review
From a Canadian perspective, there has been a limited discussion on the frontline management of young, fit patients with chronic lymphocytic leukemia (CLL). The prevalence of this population ranges between 2 and 22 per 100,000 persons in Canada and varies by region. Until recently, fixed-duration fludarabine-based chemoimmunotherapy (CIT) was the primary treatment option in Canada for this patient population. The ECOG1912 trial has since demonstrated that ibrutinib and rituximab therapy are as effective as fludarabine-cyclophosphamide-rituximab (FCR) in this population. The ALLIANCE trial showed that rituximab added no incremental benefit to ibrutinib. Canadian payors and physicians adopted ibrutinib monotherapy as the CLL standard of care, even in the young, fit population, although frontline ibrutinib therapy is often reimbursed by provincial public drug plans only in patients with high-risk disease or those who are unfit to receive fludarabine. Young, fit patients with CLL and their physicians may now choose between continuous ibrutinib monotherapy and fixed-duration CIT with FCR. Factors affecting this choice include patient preference and the short- and long-term toxicity profiles of both regimens, and a risk-based algorithm is provided. As new continuous-therapy options enter the market, all treatment choices present benefits and risks that must be communicated to the patient.
Topics: Antineoplastic Combined Chemotherapy Protocols; Canada; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Pyrazoles; Rituximab
PubMed: 34677244
DOI: 10.3390/curroncol28050326 -
Oncology Nursing Forum Jul 2020In oncology, chemotherapy treatment delays potentially jeopardize patient safety and impede progress toward disease remission. The purpose of this study was to examine...
PURPOSE
In oncology, chemotherapy treatment delays potentially jeopardize patient safety and impede progress toward disease remission. The purpose of this study was to examine the causes and consequences of chemotherapy treatment delays and possible solutions to improve quality of care.
PARTICIPANTS & SETTING
The current authors selected a purposive sample of eight ambulatory oncology practices for ethnographic site visits, which lasted five days each.
METHODOLOGIC APPROACH
The authors conducted 290 observation hours, including clinician shadowing, and 46 semistructured interviews with clinicians (oncology nurses, physicians, and advanced practice providers). Deductive and inductive thematic analysis was performed on all data.
FINDINGS
The authors identified four primary themes from the analysis that affect delays.
IMPLICATIONS FOR NURSING
Future investigations should examine nurses' communication practices in the context of timely chemotherapy administration because communication and documentation technologies within healthcare settings continuously evolve.
Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care Facilities; Drug Therapy; Female; Humans; Male; Middle Aged; Neoplasms; Oncology Nursing; Qualitative Research; Quality of Health Care; Time-to-Treatment; United States
PubMed: 32555555
DOI: 10.1188/20.ONF.417-427 -
Clinical Breast Cancer Apr 2018Trastuzumab improves survival outcomes for patients with HER2-positive (HER2) breast cancer, yet not all such women receive this important therapy. Trastuzumab was... (Review)
Review
Trastuzumab improves survival outcomes for patients with HER2-positive (HER2) breast cancer, yet not all such women receive this important therapy. Trastuzumab was approved by the US Food and Drug Administration in 1998 and the European Medicines Agency in 2000 as treatment for HER2 metastatic breast cancer (MBC). Observational studies between 2000 and 2015 in patients with HER2 MBC suggest that nearly 12% in the United States, 27% to 54% in Europe, and 27.1% to 49.2% in China did not receive trastuzumab or any other HER2-targeted agent as first- and/or later-line for treatment of metastatic disease. In 2006, both agencies approved trastuzumab as adjuvant therapy for patients with HER2 early breast cancer (EBC). Observational studies on real-world treatment patterns for HER2 EBC between 2005 and 2015 suggest that 19.1% to 59.5% of patients across regions of North America, Europe, Australia, New Zealand, and China did not receive (neo)adjuvant trastuzumab. Data suggest that some patient subgroups, including older patients, those with HER2/hormone receptor-positive disease, and women with small and/or node-negative HER2 tumors, were less likely to receive anti-HER2 therapy. Barriers to accessing trastuzumab are multifactorial and include issues related to drug funding and high treatment costs for patients that have been reported worldwide. Herein, we review available literature on the use of, and barriers to, treatment with trastuzumab in patients with HER2 breast cancer. We also discuss how the availability of safe and effective biosimilars might increase access to trastuzumab and allow greater use of anti-HER2 therapy, potentially improving patient outcomes.
Topics: Antineoplastic Combined Chemotherapy Protocols; Australia; Biosimilar Pharmaceuticals; Breast Neoplasms; Chemotherapy, Adjuvant; China; Disease-Free Survival; Drug Costs; Europe; Fees, Pharmaceutical; Female; Global Health; Health Services Needs and Demand; Humans; Mastectomy; Neoadjuvant Therapy; New Zealand; Patient Selection; Receptor, ErbB-2; Trastuzumab; United States
PubMed: 29525430
DOI: 10.1016/j.clbc.2018.01.006 -
Annals of the Academy of Medicine,... Jan 2010Patients with peritoneal carcinomatosis (PC) usually have dismal prognoses, even with traditional systemic therapy. Peritonectomy or cytoreductive surgery (CRS) has been... (Review)
Review
INTRODUCTION
Patients with peritoneal carcinomatosis (PC) usually have dismal prognoses, even with traditional systemic therapy. Peritonectomy or cytoreductive surgery (CRS) has been used to treat selected patients. It is also commonly used in the management of pseudomyxoma peritonei (PMP), often in combination with hyperthermic intraperitoneal chemotherapy (HIPEC).
METHODS AND RESULTS
In the present review article, the indications for CRS and HIPEC are examined, along with its technical aspects, resulting morbidity and mortality. Patients with documented peritoneal carcinomatosis from colorectal and ovarian cancer or PMP, absence of extra-abdominal metastases and liver parenchymal metastases and with an ECOG performance status of <2 should be considered for CRS and HIPEC.
CONCLUSION
It is important to recognise the role of and indications for CRS and HIPEC. Biologic factors of the disease and completeness of resection are important prognostic factors. Cytoreductive surgery, combined with intraperitoneal chemotherapy, can improve survival in selected patients with peritoneal-based malignancies.
Topics: Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Humans; Hyperthermia, Induced; Infusions, Parenteral; Patient Selection; Peritoneal Neoplasms; Survival Analysis
PubMed: 20126816
DOI: No ID Found -
The New England Journal of Medicine Aug 2023Partial resistance of to the artemisinin component of artemisinin-based combination therapies, the most important malaria drugs, emerged in Southeast Asia and now...
BACKGROUND
Partial resistance of to the artemisinin component of artemisinin-based combination therapies, the most important malaria drugs, emerged in Southeast Asia and now threatens East Africa. Partial resistance, which manifests as delayed clearance after therapy, is mediated principally by mutations in the kelch protein K13 (PfK13). Limited longitudinal data are available on the emergence and spread of artemisinin resistance in Africa.
METHODS
We performed annual surveillance among patients who presented with uncomplicated malaria at 10 to 16 sites across Uganda from 2016 through 2022. We sequenced the gene encoding kelch 13 () and analyzed relatedness using molecular methods. We assessed malaria metrics longitudinally in eight Ugandan districts from 2014 through 2021.
RESULTS
By 2021-2022, the prevalence of parasites with validated or candidate resistance markers reached more than 20% in 11 of the 16 districts where surveillance was conducted. The PfK13 469Y and 675V mutations were seen in far northern Uganda in 2016-2017 and increased and spread thereafter, reaching a combined prevalence of 10 to 54% across much of northern Uganda, with spread to other regions. The 469F mutation reached a prevalence of 38 to 40% in one district in southwestern Uganda in 2021-2022. The 561H mutation, previously described in Rwanda, was first seen in southwestern Uganda in 2021, reaching a prevalence of 23% by 2022. The 441L mutation reached a prevalence of 12 to 23% in three districts in western Uganda in 2022. Genetic analysis indicated local emergence of mutant parasites independent of those in Southeast Asia. The emergence of resistance was observed predominantly in areas where effective malaria control had been discontinued or transmission was unstable.
CONCLUSIONS
Data from Uganda showed the emergence of partial resistance to artemisinins in multiple geographic locations, with increasing prevalence and regional spread over time. (Funded by the National Institutes of Health.).
Topics: Animals; Humans; Artemisinins; Benchmarking; Parasites; Uganda; Drug Resistance; Malaria; Protozoan Proteins
PubMed: 37611122
DOI: 10.1056/NEJMoa2211803 -
Schizophrenia Research Jun 2012To assess the prevalence and correlates of antipsychotic polypharmacy (APP) across decades and regions. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess the prevalence and correlates of antipsychotic polypharmacy (APP) across decades and regions.
METHODS
Electronic PubMed/Google Scholar search for studies reporting on APP, published from 1970 to 05/2009. Median rates and interquartile ranges (IQR) were calculated and compared using non-parametric tests. Demographic and clinical variables were tested as correlates of APP in bivariate and meta-regression analyses.
RESULTS
Across 147 studies (1,418,163 participants, 82.9% diagnosed with schizophrenia [IQR=42-100%]), the median APP rate was 19.6% (IQR=12.9-35.0%). Most common combinations included first-generation antipsychotics (FGAs)+second-generation antipsychotics (SGAs) (42.4%, IQR=0.0-71.4%) followed by FGAs+FGAs (19.6%, IQR=0.0-100%) and SGAs+SGAs (1.8%, IQR=0.0-28%). APP rates were not different between decades (1970-1979:28.8%, IQR=7.5-44%; 1980-1989:17.6%, IQR=10.8-38.2; 1990-1999:22.0%, IQR=11-40; 2000-2009:19.2% IQR=14.4-29.9, p=0.78), but between regions, being higher in Asia and Europe than North America, and in Asia than Oceania (p<0.001). APP increased numerically by 34% in North America from the 1980s 12.7%) to 2000s (17.0%) (p=0.94) and decreased significantly by 65% from 1980 (55.5%) to 2000 (19.2%) in Asia (p=0.03), with non-significant changes in Europe. APP was associated with inpatient status (p<0.001), use of FGAs (p<0.0001) and anticholinergics (<0.001), schizophrenia (p=0.01), less antidepressant use (p=0.02), greater LAIs use (p=0.04), shorter follow-up (p=0.001) and cross-sectional vs. longitudinal study design (p=0.03). In a meta-regression, inpatient status (p<0.0001), FGA use (0.046), and schizophrenia diagnosis (p=0.004) independently predicted APP (N=66, R(2)=0.44, p<0.0001).
CONCLUSIONS
APP is common with different rates and time trends by region over the last four decades. APP is associated with greater anticholinergic requirement, shorter observation time, greater illness severity and lower antidepressant use.
Topics: Antipsychotic Agents; Asia; Drug Therapy; Drug Therapy, Combination; Europe; Humans; North America; Oceania; Polypharmacy; Schizophrenia
PubMed: 22534420
DOI: 10.1016/j.schres.2012.03.018 -
European Journal of Pharmacology Sep 2018Quantitative techniques improve our understanding of tumor volume data for combination treatments and its translation across in vivo models and species. The focus of... (Review)
Review
Quantitative techniques improve our understanding of tumor volume data for combination treatments and its translation across in vivo models and species. The focus of this paper is therefore on understanding in vivo data, highlighting key structural elements of pharmacodynamic tumor models, and challenging these methods from a translational point of view. We introduce the concept of Tumor Static Exposure (TSE) both for single and multiple combined anticancer agents. The TSE curve separates all possible exposure combinations into regions of tumor growth and tumor shrinkage. Moreover, the degree of curvature of the TSE curve indicates the degree of synergy or antagonism. We demonstrate the TSE approach by two case studies. The first examines a combination of the drugs cetuximab and cisplatin. The TSE curve associated with this combination reveals a weak synergistic effect, suggesting only modest gains from combination therapy. The second case study examines combinations of ionizing radiation and a radiosensitizing agent. In this case, the TSE curve exhibits a pronounced curvature, indicating a strong synergistic effect; tumor regression can be achieved at significantly lower exposure levels and/or radiation doses. Finally, an allometric approach to human dose prediction demonstrates the translational power of the model and the TSE concept. We conclude that the TSE approach, which embodies model-based measures of both drug (potency) and target properties (tumor growth rate), has a strong potential for ranking of compounds, supporting compound selection, and translating preclinical findings to humans.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Humans; Neoplasms
PubMed: 30036534
DOI: 10.1016/j.ejphar.2018.07.041 -
Asian Pacific Journal of Cancer... Oct 2022To characterize the compliance status of adjuvant endocrine therapy (aET) and its relationship with disease-free survival (DFS) in hormone receptor-positive (HR+) and...
Full Compliance of Adjuvant Endocrine Therapy Is Associated with Higher Disease-Free Survival in Hormone Receptor-Positive and HER2-Negative Chinese Breast Cancer Patients with First Tumor Recurrence.
PURPOSE
To characterize the compliance status of adjuvant endocrine therapy (aET) and its relationship with disease-free survival (DFS) in hormone receptor-positive (HR+) and HER2-negative (HER2-) in Chinese breast cancer (BC) patients with first tumor recurrence.
METHODS
All women with primary unilateral stage I - III HR+HER2- BC and first tumor recurrence in 2008 - 2018 at our institution were identified. Full (vs. none/partial) compliance of aET was classified from records. Multivariate Cox regression estimated the hazard ratio (HR), its 95% confidence interval (CI), and p value. DFS. Covariates included age, T stage, N stage, pathology, tumor grade, LVI, chemotherapy, radiotherapy. Results: A total 258 patients had average age 47.4 years at BC diagnosis and median DFS 31.7 months. Patients with ipsilateral (contralateral) region and organ recurrence were 47.7% (19.8%) and 71.9%. Compared to the patients with none/partial compliance of aET, the full compliance patients (54.3% ) had a higher DFS (median 35.0 vs. 25.2 months, p=0.009). Multivariate analysis showed that the full compliance of aET was associated with a lower HR 0.614 (95%CI 0.467 - 0.807, p<0.001) on recurrence. Early discontinuation (67.5%, 56/83) due to the drug side effects was the top reason for partial compliance of aET.
CONCLUSIONS
Full compliance of aET was quite low in Chinese HR+HER2- BC patients. However, it was associated with a 38.6% lower risk of first tumor recurrence. To search for effective tools to improve the compliance of aET in this population should be stressed.
Topics: Female; Humans; Middle Aged; Breast Neoplasms; Chemotherapy, Adjuvant; China; Disease-Free Survival; Neoplasm Recurrence, Local; Receptor, ErbB-2
PubMed: 36308366
DOI: 10.31557/APJCP.2022.23.10.3413 -
Economic Evaluation of First-Line Atezolizumab for Extensive-Stage Small-Cell Lung Cancer in the US.Frontiers in Public Health 2021This study evaluated the cost-effectiveness of atezolizumab + chemotherapy vs. chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (SCLC) in...
This study evaluated the cost-effectiveness of atezolizumab + chemotherapy vs. chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (SCLC) in the United States (US). The three health states partitioned survival (PS) model was used over the lifetime. Effectiveness and safety data were derived from the IMpower133 trial. The parametric survival model and mixture cure model were used for the atezolizumab + chemotherapy group to explore the long-term uncertainty of the effect of immunotherapy, and the parametric survival model was used for the chemotherapy group. Costs were derived from the pricing files of Medicare and Medicaid Services, and utility values were derived from previous studies. Sensitivity analyses were performed to observe model stability. If the mixture cure model was considered for the intervention group, compared with chemotherapy alone, atezolizumab + chemotherapy yielded an additional 0.11 quality-adjusted life-years (QALYs), with an incremental cost of US$84,257. The incremental cost-utility ratio (ICUR) was US$785,848/QALY. If the parametric survival model was considered for the intervention group, atezolizumab + chemotherapy yielded an additional 0.10 QALYs, with an incremental cost of US$84,257; the ICUR was US$827,610/QALY. In the one-way sensitivity analysis, progression-free (PF) and postprogression (PP) utilities were the main drivers. In the scenario analysis (PF utility = 0.673, PP utility = 0.473), the results showed that the ICUR was US$910,557/QALY and US$965,607/QALY when the mixture cure model and parametric survival model was considered for the intervention group, respectively. In the PSA, the probabilities that atezolizumab + chemotherapy would not be cost-effective were 100% if the willingness-to-pay threshold was US$100,000/QALY. The findings of the present analysis suggest that atezolizumab + chemotherapy is not cost-effective in patients receiving first-line treatment for extensive-stage SCLC in the US.
Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Humans; Lung Neoplasms; Medicare; United States
PubMed: 33889559
DOI: 10.3389/fpubh.2021.650392 -
World Journal of Surgical Oncology May 2021Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective routine treatments for colorectal peritoneal metastasis (PM). However,...
Neoadjuvant chemotherapy followed by hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal metastasis: a retrospective study of its safety and efficacy.
BACKGROUND
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective routine treatments for colorectal peritoneal metastasis (PM). However, the safety and efficacy of neoadjuvant chemotherapy (NAC) before CRS+HIPEC are poorly understood. Therefore, this study aimed to assess the perioperative safety and long-term efficacy of NAC prior to CRS+HIPEC for patients with synchronous colorectal PM.
METHODS
Patients with synchronous colorectal PM who received NAC prior to CRS+HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. The clinicopathologic characteristics, perioperative parameters, and survival rates of patients who underwent CRS+HIPEC with NAC (NAC group) and patients who underwent CRS+HIPEC without NAC (non-NAC group) were compared.
RESULTS
The study enrolled 52 patients, with 20 patients in the NAC group and 32 in the non-NAC group. In the NAC group, the proportion of patients with a peritoneal carcinomatosis index (PCI) score < 12 was significantly higher than that in the non-NAC group (80.0% vs 50.0%, P = 0.031), and more patients achieved complete cytoreduction (80.0% vs 46.9%, P = 0.018). The two groups had comparable grade III/IV complications and similar reoperation and mortality rates (P > 0.05). However, patients who received NAC had lower platelet counts (151.9 vs 197.7 × 10/L, P = 0.036) and neutrophil counts (4.7 vs 7.2 × 10/L, P = 0.030) on postoperative day 1. More patients survived for 2 years in the NAC group than in the non-NAC group (67.4% vs 32.2%, respectively, P = 0.044). However, the completeness of cytoreduction score (HR, 2.99; 95% CI, 1.14-7.84; P = 0.026), rather than NAC, was independently associated with overall survival (OS) in the multivariate analysis after controlling for confounding factors.
CONCLUSION
NAC administration before CRS+HIPEC can be regarded as safe and feasible for patients with colorectal PM with comparably low mortality rates and acceptable morbidity rates. Nevertheless, large-sample randomized controlled studies are needed to confirm whether the administration of NAC before CRS+HIPEC confers a survival benefit to patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; China; Colorectal Neoplasms; Combined Modality Therapy; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Hyperthermic Intraperitoneal Chemotherapy; Neoadjuvant Therapy; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Survival Rate
PubMed: 34001125
DOI: 10.1186/s12957-021-02255-w