Evaluation of Cockcroft-Gault (CG) and abbreviated modified diet in renal disease (MDRD) formulae in dosing of cancer drugs other than carboplatin

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2522-2522
Author(s):  
S. A. Jennings ◽  
M. L. de Lemos ◽  
A. Levin ◽  
N. Murray
Keyword(s):  
Cancer Patients ◽  
Initial Dose ◽  
Dose Adjustment ◽  
Specific Treatment ◽  
Secondary Outcome ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Treatment Protocols ◽  
Cancer Agency ◽  
Similar Accuracy

2522 Background: Glomerular filtration rate (GFR) is often used to determine initial dosing of renally-excreted cancer drugs. Estimated GFR (eGFR) can be calculated using serum creatinine (SrCr) -based formulae such as CG and MDRD. MDRD is more accurate in non-cancer patients, does not require patient weight, and is reported automatically by all laboratories in British Columbia (BC). We previously showed that CG and MDRD have similar accuracy for carboplatin dosing in patients with gynecological malignancies. We now examine dosing of all renally-excreted cancer drugs in the general cancer population. Since this setting does not include routine measurement of GFR, we report the concordance of eGFR derived from CG and MDRD. Methods: Patient data were collected retrospectively at the BC Cancer Agency. The primary outcome was concordance of eGFR derived from CG and MDRD, using the method of Bland and Altman. A difference of ≥ 30% was assumed to be clinically significant because this difference would usually lead to dose adjustment based on reclassification of renal function. The secondary outcome was the proportion of patients who would have received a different initial dose due to difference in eGFR. Each patient’s dose was determined from dose adjustment tables stated in specific treatment protocols. Results: 313 patients were evaluated: 40% male, median 56y, 67.5kg, 166cm, SrCr 74micromol/L. Median eGFR derived from CG and MDRD were 86.8mL/min and 87.6mL/min, respectively. A difference of ≥ 30% in eGFR was found in 17.9% (56/313) of patients. 8.6% (27/313) of patients would have received a different dose due to difference in eGFR; of these, 67% (18/27) would have received a higher dose. Conclusions: There is good concordance of eGFR derived from CG and MDRD for most cancer patients, with less than 10% of patients expected to receive a different initial dose of chemotherapy. MDRD may be a reasonable alternative to CG for dosing of any renally-excreted cancer drug. No significant financial relationships to disclose.

Better treatment at what cost? A study of myeloma spending.

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 60-60
Author(s):  
Rohini Naipaul ◽  
Elena Mow ◽  
Rebecca Mercer ◽  
Lyndee Yeung ◽  
Scott Gavura ◽  
...  
Keyword(s):  
Drug Costs ◽  
Drug Benefit ◽  
Fiscal Year ◽  
Cancer Drug ◽  
Public Expenditures ◽  
Publicly Funded ◽  
Cancer Drugs ◽  
Treatment Protocols ◽  
Pricing Policies ◽  
Funding Program

60 Background: Multiple myeloma represents less than 1.5% of new cancer cases in Canada. Currently, the estimated median overall survival is at least 5-6 years, primarily driven by therapeutic advances over the past decade. As treatment protocols routinely use doublet and triplet combinations, there are increasing concerns about the ability of health systems to afford growing costs of treatment. To inform system planning in Ontario, we examined trends in costs and utilization of myeloma drugs funded by Ontario’s New Drug Funding Program (NDFP) and the Ontario Drug Benefit program (ODB). Methods: NDFP primarily funds IV cancer drugs while ODB funds take-home cancer drugs (THCD). Treatment volumes and government costs, including drug costs and pharmacy fees where applicable, were obtained from ODB and NDFP claims data. Based on the available data, trends were examined from the 2010/11 to the second quarter of the 2019/20 fiscal year. Results: A total of 7 myeloma drugs (3-IV cancer drugs, 4-THCD) were examined. Over 9 years (2010/11 - 2018/19), spending on publicly-funded myeloma drugs increased by 303% while treatment volumes increased by 116%. Between 2014/15 and 2018/19, bortezomib spending decreased by 72%, largely due to generic pricing policies, while lenalidomide spending increased by 158%, likely due to new indications. By 2018/19, these 7 drugs accounted for 17% of the total cancer drug costs under Ontario's publicly funded programs. NDFP spending on IV cancer drugs by the second quarter of 2019/20 has surpassed the annual expenditures in 2018/19 due to the addition of daratumumab. Conclusions: Since 2010/11, growth in Ontario's public expenditures on myeloma drugs has outpaced savings from pricing policies and this growth is mainly driven by the high cost of the novel agents.

scholarly journals Effects of Herbal Medicine Use on Adherence to Conventional Anticancer Drugs

2020 ◽  
pp. 1-20
Author(s):  
Christine Karungi ◽  
Philip Asiimwe ◽  
Conrad Ssentongo ◽  
Sharon Primah Tuhaise ◽  
Joseph Oloro
Keyword(s):  
Herbal Medicine ◽  
Cancer Patients ◽  
Anticancer Drugs ◽  
Herbal Medicines ◽  
Referral Hospital ◽  
Secondary Outcome ◽  
Cancer Drugs ◽  
Medicine Use ◽  
Regional Referral Hospital ◽  
Anti Cancer

Background: Use of herbal medicines alongside conventional anticancer drugs is common among cancer patients. This may potentially cause reduced adherence to conventional anti-cancer drugs, unpredictable side effects and unknown drug-herb interactions. This in the long run could result in poor clinical outcomes. Aim: This study was conducted to investigate how use of herbal medicines affects adherence to conventional anti-cancer drugs, to determine the proportion of patients using both conventional and herbal anticancer medicines and to identify the common herbal medicines used alongside conventional anti-cancer drugs by patients at the Mbarara Regional Referral Hospital Oncology unit. Methods and Findings: A cross-sectional study was conducted in the oncology clinic of Mbarara Regional Referral Hospital found in Mbarara district, Uganda. Data was collected between 20th March and 20th April 2019 from 122 participants who met the inclusion criteria with subsequent consenting. Our primary outcome was adherence and secondary outcome was to investigate whether cancer patients use herbal medicines alongside conventional anti-cancer drugs. Our study had 122 patients most of them belonging to the Banyankole tribe, 75 (61.5%) being males. Of the 72 (59.02%) patients who used herbal medicine, 40 (55.56%) were males and 66.67% of the herbal users reported relief from herbal medicines. Aloe Vera was the most commonly used herb. Most of the patients 77 (63.1%) showed high adherence, this was greater in the non-herbal users than in the herbal users (COR=1.62) though this was not significant (p=0.399). Conclusion: It is most likely that majority of cancer patients use at least one herb during their course of life. The results did not show a significant relationship between herbal medicine use and adherence to conventional anti-cancer drugs. The high proportion of herbal medicine users calls for more research into the area to provide further information that can help optimize cancer treatment outcomes.

scholarly journals Pan-Cancer Integrative Analysis of Whole-Genome De novo Somatic Point Mutations Reveals 17 Cancer Types

2021 ◽  
Author(s):  
Amirreza Kazemi ◽  
Amin Ghareyazi ◽  
Kimia Hamidieh ◽  
Hamed Dashti ◽  
Maedeh Tahaei ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Molecular Mechanisms ◽  
High Throughput Sequencing ◽  
Specific Treatment ◽  
Cancer Drug ◽  
Cancer Type ◽  
Cancer Subtypes ◽  
Genotypic Analysis ◽  
Cancer Types ◽  
Pan Cancer

The advent of high throughput sequencing has enabled researchers to systematically evaluate the genetic variations in cancer, resulting in identifying many cancer-associated genes. Although cancers in the same tissue are widely categorized in the same group, they demonstrate many differences concerning their mutational profiles. Hence there is no “silver bullet” for the treatment of a cancer type. This reveals the importance of developing a pipeline to identify cancer-associated genes accurately and re-classify patients with similar mutational profiles. Classification of cancer patients with similar mutational profiles may help discover subtypes of cancer patients who might benefit from specific treatment types. In this study, we propose a new machine learning pipeline to identify protein-coding genes mutated in a significant portion of samples to identify cancer subtypes. We applied our pipeline to 12270 samples collected from the International Cancer Genome Consortium (ICGC), covering 19 cancer types. Here we identified 17 different cancer subtypes. Comprehensive phenotypic and genotypic analysis indicates distinguishable properties, including unique cancer-related signaling pathways, in which, for most of them, targeted treatment options are currently available. This new subtyping approach offers a novel opportunity for cancer drug development based on the mutational profile of patients. We also comprehensive study the causes of mutations among samples in each subtype by mining the mutational signatures, which provides important insight into their active molecular mechanisms. Some of the pathways we identified in most subtypes, including the cell cycle and the Axon guidance pathways, are frequently observed in cancer disease. Interestingly, we also identified several mutated genes and different rates of mutation in multiple cancer subtypes. In addition, our study on “gene-motif” suggests the importance of considering both the context of the mutations and mutational processes in identifying cancer-associated genes. The source codes for our proposed clustering pipeline and analysis are publicly available at: https://github.com/bcb-sut/Pan-Cancer.

Fanconi Anemia DNA Repair Pathway as a New Mechanism to Exploit Cancer Drug Resistance

2020 ◽  
Vol 20 (9) ◽  
pp. 779-787
Author(s):  
Kajal Ghosal ◽  
Christian Agatemor ◽  
Richard I. Han ◽  
Amy T. Ku ◽  
Sabu Thomas ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Dna Repair ◽  
Fanconi Anemia ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Cancer Drugs ◽  
Repair Pathway ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Cancerous Cells

Chemotherapy employs anti-cancer drugs to stop the growth of cancerous cells, but one common obstacle to the success is the development of chemoresistance, which leads to failure of the previously effective anti-cancer drugs. Resistance arises from different mechanistic pathways, and in this critical review, we focus on the Fanconi Anemia (FA) pathway in chemoresistance. This pathway has yet to be intensively researched by mainstream cancer researchers. This review aims to inspire a new thrust toward the contribution of the FA pathway to drug resistance in cancer. We believe an indepth understanding of this pathway will open new frontiers to effectively treat drug-resistant cancer.

scholarly journals DRUG REPOSITION OF NON-CANCER DRUGS FOR CANCER TREATMENTS VIA PHARMACOVIGILANCE APPROACH - REPURPOSING DRUGS IN ONCOLOGY

2019 ◽  
pp. 310-314 ◽  
Author(s):  
Mrugank Bhaskarkumar Parmar ◽  
Shital Panchal
Keyword(s):  
Statistical Analysis ◽  
Cancer Treatment ◽  
Drug Repositioning ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Management Activity ◽  
Post Marketing Surveillance ◽  
Source Data

This study for drug repositioning has been performed for the drugs which are in the market since more than a decade and they are approved with their well-established efficacy and safety in human being. Objective of this study was to reposition the existing non-cancer drug therapy for cancer treatment, which is having well characterized pharmacologic profile with more efficacy and least toxicity as anti-neoplastic agent. We have retrieved the source data from FDA Adverse Event Reporting System (FAERS) for the last 13 years covering duration from 2004 to 2016 and analysed those using pharmacovigilance approach ‘a proposed future novel pharmaceutical tool for drug reposition’. Signal management activity was performed for statistical analysis. Result of statistical analysis derived that propranolol; metformin; pioglitazone; dabigatran and nitroglycerin are the existing non-cancer drugs which deserved for their direct / indirect reposition for cancer treatment and anti-neoplastic activity. Further studies retrieving the source data from other regulatory database (e.g. Eudravigilance of EMA and VigiFlow of WHO) and post-marketing surveillance study with the same objective may adjuvant our results for the reposition of existing drugs by pharmacovigilance approach.

scholarly journals Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: a protocol for a systematic review and network meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. e033461
Author(s):  
Kyeore Bae ◽  
Si Yeon Song
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Pain Intensity ◽  
Aromatase Inhibitor ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Indirect Evidence ◽  
Secondary Outcome ◽  
Breast Cancer Patients ◽  
Patient Reported

IntroductionAromatase inhibitor-induced arthralgia (AIA) is a major adverse event of aromatase inhibitors (AIs) and leads to premature discontinuation of AI therapy in breast cancer patients. The objective of this protocol for a systematic review and network meta-analysis (NMA) is to provide the methodology to compare the change in pain intensity between different AIA treatments and demonstrate the rank probabilities for different treatments by combining all available direct and indirect evidence.Methods and analysisPubMed, the Cochrane Controlled Register of Trials (CENTRAL), EMBASE, Web of Science and ClinicalTrials.gov will be searched to identify publications in English from inception to November 2019. We will include randomised controlled trials (RCTs) assessing the effects of different treatments for AIA in postmenopausal women with stage 0–III hormone receptor-positive breast cancer. The primary endpoints will be the change in patient-reported pain intensity from baseline to post-treatment. The number of adverse events will be presented as a secondary outcome.Both pairwise meta-analysis and NMA with the Frequentist approach will be conducted. We will demonstrate summary estimates with forest plots in meta-analysis and direct and mixed evidence with a ranking of the treatments as the P-score in NMA. The revised Cochrane risk-of-bias tool for randomised trials will be used to assess the methodological quality within individual RCTs. The quality of evidence will be assessed.Ethics and disseminationAs this review does not involve individual patients, ethical approval is not required. The results of this systematic review and NMA will be published in a peer-reviewed journal. This review will provide valuable information on AIA therapeutic options for clinicians, health practitioners and breast cancer survivors.PROSPERO registration numberCRD42019136967.

Continental Divide? The Attitudes of US and Canadian Oncologists on the Costs, Cost-Effectiveness, and Health Policies Associated With New Cancer Drugs

2010 ◽  
Vol 28 (27) ◽  
pp. 4149-4153 ◽  
Author(s):  
Scott R. Berry ◽  
Chaim M. Bell ◽  
Peter A. Ubel ◽  
William K. Evans ◽  
Eric Nadler ◽  
...  
Keyword(s):  
United States ◽  
Health Care ◽  
Cost Effectiveness ◽  
Health Care Systems ◽  
The United States ◽  
Drug Costs ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Care Systems ◽  
Effective Treatments

Purpose Oncologists in the United States and Canada work in different health care systems, but physicians in both countries face challenges posed by the rising costs of cancer drugs. We compared their attitudes regarding the costs and cost-effectiveness of medications and related health policy. Methods Survey responses of a random sample of 1,355 United States and 238 Canadian medical oncologists (all outside of Québec) were compared. Results Response rate was 59%. More US oncologists (67% v 52%; P < .001) favor access to effective treatments regardless of cost, while more Canadians favor access to effective treatments only if they are cost-effective (75% v 58%; P < .001). Most (84% US, 80% Canadian) oncologists state that patient out-of-pocket costs influence their treatment recommendations, but less than half the respondents always or frequently discuss the costs of treatments with their patients. The majority of oncologists favor more use of cost-effectiveness data in coverage decisions (80% US, 69% Canadian; P = .004), but fewer than half the oncologists in both countries feel well equipped to use cost-effectiveness information. Majorities of oncologists favor government price controls (57% US, 68% Canadian; P = .01), but less than half favor more cost-sharing by patients (29% US, 41% Canadian; P = .004). Oncologists in both countries prefer to have physicians and nonprofit agencies determine whether drugs provide good value. Conclusion Oncologists in the United States and Canada generally have similar attitudes regarding cancer drug costs, cost-effectiveness, and associated policies, despite practicing in different health care systems. The results support providing education to help oncologists in both countries use cost-effectiveness information and discuss drug costs with their patients.

scholarly journals Pre-Operative Decitabine in Colon Cancer Patients: Analyses on WNT Target Methylation and Expression

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2357
Author(s):  
Janneke F. Linnekamp ◽  
Raju Kandimalla ◽  
Evelyn Fessler ◽  
Joan H. de Jong ◽  
Hans M. Rodermond ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Operative Treatment ◽  
Primary Outcome ◽  
Target Genes ◽  
Primary Objective ◽  
Secondary Outcome ◽  
Dna Hypermethylation ◽  
Line1 Methylation ◽  
Stage Ii Colon Cancer

DNA hypermethylation is common in colon cancer. Previously, we have shown that methylation of WNT target genes predicts poor prognosis in stage II colon cancer. The primary objective of this study was to assess whether pre-operative treatment with decitabine can decrease methylation and increase the expression of WNT target genes APCDD1, AXIN2 and DKK1 in colon cancer patients. A clinical study was conducted, investigating these potential effects of decitabine in colon cancer patients (DECO). Patients were treated two times with 25 mg/m2 decitabine before surgery. Methylation and expression of LINE1 and WNT target genes (primary outcome) and expression of endogenous retroviral genes (secondary outcome) were analysed in pre- and post-treatment tumour samples using pyrosequencing and rt-PCR. Ten patients were treated with decitabine and eighteen patients were used as controls. Decitabine treatment only marginally decreased LINE1 methylation. More importantly, no differences in methylation or expression of WNT target or endogenous retroviral genes were observed. Due to the lack of an effect on primary and secondary outcomes, the study was prematurely closed. In conclusion, pre-operative treatment with decitabine is safe, but with the current dosing, the primary objective, increased WNT target gene expression, cannot be achieved.

scholarly journals Impact of the pan-Canadian Oncology Drug Review on provincial concordance with respect to cancer drug funding decisions and time to funding

2017 ◽  
Vol 24 (5) ◽  
pp. 295 ◽  
Author(s):  
A. Srikanthan ◽  
H. Mai ◽  
N. Penner ◽  
E. Amir ◽  
A. Laupacis ◽  
...  
Keyword(s):  
Linear Models ◽  
Drug Product ◽  
Median Number ◽  
Cancer Drug ◽  
Cancer Drugs ◽  
Oncology Drug ◽  
Before And After ◽  
Canadian Provinces ◽  
The Impact ◽  
Drug Review

Background The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 to address uneven drug coverage and lack of transparency with respect to the various provincial cancer drug review processes in Canada. We evaluated the impact of the pcodr on provincial decision concordance and time from Notice of Compliance (noc) to drug funding.Methods In a retrospective review, Health Canada’s Drug Product Database was used to identify new indications for cancer drugs between January 2003 and May 2014, and provincial formulary listings for drug-funding dates and decisions between 1 January 2003 and 31 December 2014 were retrieved. Multiple linear models and quantile regressions were used to evaluate changes in time to decision-making before and after the implementation of the pcodr. Agreement of decisions between provinces was evaluated using kappa statistics.Results Data were available from 9 provinces (all Canadian provinces except Quebec), identifying 88 indications that represented 51 unique cancer drugs. Two provinces lacked available data for all 88 indications at the time of data collection. Interprovincial concordance in drug funding decisions significantly increased after the pcodr’s implementation (Brennan-Prediger coefficient: 0.54 pre-pcodr vs. 0.78 post-pcodr; p = 0.002). Nationwide, the median number of days from Health Canada’s noc date to the date of funding significantly declined (to 393 days from 522 days, p < 0.001). Exploratory analyses excluding provinces with incomplete data did not change the results.Conclusions After the implementation of the pcodr, greater concordance in cancer drug funding decisions between provinces and decreased time to funding decisions were observed.

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