scholarly journals Retrospective cohort analysis of prescription patterns of cancer medications during periods of drug stockouts in Botswana

BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e049574
Author(s):  
Sonya Davey ◽  
Surbhi Grover ◽  
Warren B Bilker ◽  
Dipho I Setlhako ◽  
Tlotlo B Ralefala ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Cohort ◽  
Cohort Analysis ◽  
Kaposi Sarcoma ◽  
Sub Saharan Africa ◽  
Secondary Outcome ◽  
Cancer Drug ◽  
Breast Cancer Patients ◽  
Prescription Patterns ◽  
The Impact

ObjectiveCancer drug stockouts occur at high frequencies globally, however, their effects on treatment are understudied in sub-Saharan Africa (SSA). We aimed to determine whether causes of suboptimal cancer treatment prescriptions differed between periods of stockout and full treatment supply.DesignA retrospective cohort study of systemic therapy prescriptions for patients diagnosed with the twelve most common solid tumour cancers treated in 2016.SettingPrincess Marina Hospital in Gaborone, Botswana.ParticipantsPatients in the retrospective cohort who experienced any suboptimal treatment events, defined as ≥7 days delay or switch from guideline-concordant initiated therapy.Primary and secondary outcome measuresFrequency of delays and patterns of prescription changes for specific regimens and cancer types.Results167/378 patients contributed to 320 suboptimal events (115 therapy switches, 167 delays and 38 events with both), over 1452 total chemotherapy cycles received. Events during stockout were 43% delays, 43% switches and 14% both during stockout periods and 67.2% delays, 24.4% switches and 8.4% both during non-stockout periods (p<0.001). Majority of switches involved de-escalation of initially prescribed guideline-recommended regimens in patients with breast cancer, Kaposi sarcoma and patients with colorectal cancer, which occurred more frequently during periods of drug stockouts. Among patients with breast cancer, substitution of docetaxel for paclitaxel event occurred exclusively during paclitaxel drug stockout. Delays of ≥7 days events were most frequent in breast cancer patients receiving paclitaxel during stockout, and combination doxorubicin and cyclophosphamide even during periods of non-stockout.ConclusionsThe aetiology of suboptimal events differed during stockout and non-stockout periods. Prescription patterns that involved de-escalation of initiated therapy and substitution of paclitaxel with docetaxel occurred frequently during periods of drug stockout. Further research needs to be conducted to understand the impact of stockout on survival and barriers to maintaining essential cancer medicines supplies in SSA, and the factors driving frequent delays in therapy delivery.

Prescription patterns and associated cost during periods of cancer drug stockouts in a resource-limited setting.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18129-e18129
Author(s):  
Sonya Davey ◽  
Surbhi Grover ◽  
Dipho Irene I Setlhako ◽  
Tlotlo Bathethi Ralefala ◽  
Patrick Manshimba ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Systemic Chemotherapy ◽  
Drug Prescription ◽  
Sub Saharan Africa ◽  
Cancer Drug ◽  
Clinical Effects ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Prescription Patterns

e18129 Background: Cancer drug stockouts occur at high frequencies globally, however their clinical effects are understudied in sub-Saharan Africa (SSA). We aim to describe prescription patterns and cost of systemic chemotherapy in cancer patients in Botswana during periods of stockout. Methods: Using a retrospective cohort study of the ten most common solid tumor malignancies treated with systemic chemotherapy at Princess Marina Hospital (PMH), Gaborone in 2016, we conducted a subset analysis of suboptimal events, defined as a cycle with ≥ 7 days delay or therapy switch from initiated guideline regimen, that occurred during drug stockout vs non-stockout periods. We estimated financial cost of therapy per cycle using Management Sciences for Health International Price Indicator Guide. Chi-squared and Wilcoxon rank sum were used for comparisons. Results: 167/378 patients contributed to 320 suboptimal events. 63% (201/320) of events occurred during a drug stockout, of which 43%, 43% and 14% were delays, switches, or both, respectively. There were significantly more delays (56% vs 44%, p < .0001) and switches (75% vs 26%, p < .0001) during stockout periods vs no stockout. The majority of switches during drug stockouts occurred in breast cancer patients receiving curative therapy: 48% (20/42) were “paclitaxel + trastuzumab” ($4673) to “paclitaxel alone” ($35) in HER2 positive patients resulting in a 99% cost decrease; and 29% (12/42) were paclitaxel ($35) to docetaxel ($108) resulting in a 209% cost increase per cycle switched. Colon cancer patients receiving palliative-intent therapy were the second most frequent patients with therapy switches during stockout periods: 42% (8/19) were “capecitabine + oxaliplatin” ($259) to “capecitabine alone” ($105) resulting in a 59% cost decrease. Conclusions: Breast cancer patients form the majority of patients treated with systemic chemotherapy at PMH and experienced the most delays and switches in therapy during drug stockout periods. Changes in drug prescription patterns during stockout periods may be associated with switches leading to inferior but less costly regimens, and in some cases costly regimens with higher toxicity. Interventions that minimize cancer drug stockouts are imperative and further studies to understand impact of stockout on survival are needed in SSA.

scholarly journals Impact of variants in ATP-binding cassette transporters on breast cancer treatment

2020 ◽  
Vol 21 (18) ◽  
pp. 1299-1310
Author(s):  
Qingyang Xiao ◽  
Yitian Zhou ◽  
Volker M Lauschke
Keyword(s):  
Breast Cancer ◽  
Rare Variants ◽  
Therapy Response ◽  
Cancer Drug ◽  
Atp Binding ◽  
Breast Cancer Patients ◽  
Cancer Drug Resistance ◽  
The Impact ◽  
Substantial Interest ◽  
Atp Binding Cassette

There has been substantial interest in the impact of ATP-binding cassette (ABC) transporter variability on breast cancer drug resistance. Here, we provide a systematic review of ABC variants in breast cancer therapy. Notably, most studies used small heterogeneous cohorts and their identified associations lack statistical stringency, replication and mechanistic support. We conclude that commonly studied ABC polymorphisms are not suitable to accurately predict therapy response or toxicity in breast cancer patients and cannot guide treatment decisions. However, recent research shows that ABC transporters harbor a plethora of rare variants with individually small effect sizes, and we argue that a shift in strategy from target variant interrogation to comprehensive profiling might hold promise to drastically improve the predictive power of outcome models.

scholarly journals CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jennifer K. Lang ◽  
Badri Karthikeyan ◽  
Adolfo Quiñones-Lombraña ◽  
Rachael Hageman Blair ◽  
Amy P. Early ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Care Center ◽  
Left Ventricular ◽  
The Body ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Echocardiographic Parameters ◽  
The Impact

Abstract Background The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact of CBR3 V244M on the risk for anthracycline-related cardiotoxicity in adult cohorts. Objectives This study evaluated the presence of associations between CBR3 V244M genotype status and changes in echocardiographic parameters in breast cancer patients undergoing doxorubicin treatment. Methods We recruited 155 patients with breast cancer receiving treatment with doxorubicin (DOX) at Roswell Park Comprehensive Care Center (Buffalo, NY) to a prospective single arm observational pharmacogenetic study. Patients were genotyped for the CBR3 V244M variant. 92 patients received an echocardiogram at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Apical two-chamber and four-chamber echocardiographic images were used to calculate volumes and left ventricular ejection fraction (LVEF) using Simpson’s biplane rule by investigators blinded to all patient data. Volumetric indices were evaluated by normalizing the cardiac volumes to the body surface area (BSA). Results Breast cancer patients with CBR3 GG and AG genotypes both experienced a statistically significant reduction in LVEF at 6 months following initiation of DOX treatment for breast cancer compared with their pre-DOX baseline study. Patients homozygous for the CBR3 V244M G allele (CBR3 V244) exhibited a further statistically significant decrease in LVEF at 6 months following DOX therapy in comparison with patients with heterozygous AG genotype. We found no differences in age, pre-existing cardiac diseases associated with myocardial injury, cumulative DOX dose, or concurrent use of cardioprotective medication between CBR3 genotype groups. Conclusions CBR3 V244M genotype status is associated with changes in echocardiographic parameters suggestive of early anthracycline-related cardiomyopathy in subjects undergoing chemotherapy for breast cancer.

scholarly journals Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1992
Author(s):  
Max Seidensticker ◽  
Matthias Philipp Fabritius ◽  
Jannik Beller ◽  
Ricarda Seidensticker ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Disease ◽  
Positive Impact ◽  
Metastatic Breast ◽  
Normal Liver ◽  
Liver Parenchyma ◽  
Breast Cancer Patients ◽  
Radiation Induced ◽  
The Impact

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

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.

scholarly journals PITX2 DNA-Methylation: Predictive versus Prognostic Value for Anthracycline-Based Chemotherapy in Triple-Negative Breast Cancer Patients

Breast Care ◽  
2020 ◽  
pp. 1-9
Author(s):  
Rudolf Napieralski ◽  
Gabriele Schricker ◽  
Gert Auer ◽  
Michaela Aubele ◽  
Jonathan Perkins ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Predictive Value ◽  
Untreated Patient ◽  
Triple Negative ◽  
Statistical Significance ◽  
Breast Cancer Patients ◽  
The Impact

<b><i>Background:</i></b> PITX2 DNA methylation has been shown to predict outcomes in high-risk breast cancer patients after anthracycline-based chemotherapy. To determine its prognostic versus predictive value, the impact of PITX2 DNA methylation on outcomes was studied in an untreated cohort vs. an anthracycline-treated triple-negative breast cancer (TNBC) cohort. <b><i>Material and Methods:</i></b> The percent DNA methylation ratio (PMR) of paired-like homeodomain transcription factor 2 (PITX2) was determined by a validated methylation-specific real-time PCR test. Patient samples of routinely collected archived formalin-fixed paraffin-embedded (FFPE) tissue and clinical data from 144 TNBC patients of 2 independent cohorts (i.e., 66 untreated patients and 78 patients treated with anthracycline-based chemotherapy) were analyzed. <b><i>Results:</i></b> The risk of 5- and 10-year overall survival (OS) increased continuously with rising PITX2 DNA methylation in the anthracycline-treated population, but it increased only slightly during 10-year follow-up time in the untreated patient population. PITX2 DNA methylation with a PMR cutoff of 2 did not show significance for poor vs. good outcomes (OS) in the untreated patient cohort (HR = 1.55; <i>p</i> = 0.259). In contrast, the PITX2 PMR cutoff of 2 identified patients with poor (PMR &#x3e;2) vs. good (PMR ≤2) outcomes (OS) with statistical significance in the anthracycline-treated cohort (HR = 3.96; <i>p</i> = 0.011). The results in the subgroup of patients who did receive anthracyclines only (no taxanes) confirmed this finding (HR = 5.71; <i>p</i> = 0.014). <b><i>Conclusion:</i></b> In this hypothesis-generating study PITX2 DNA methylation demonstrated predominantly predictive value in anthracycline treatment in TNBC patients. The risk of poor outcome (OS) correlates with increasing PITX2 DNA methylation.

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