scholarly journals Drug Resistance and the Role of Combination Chemotherapy in Improving Patient Outcomes

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Denise A. Yardley
Keyword(s):  
Drug Resistance ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Subsequent Development ◽  
Patient Treatment ◽  
Prior Therapy ◽  
Concurrent Use ◽  
Heavily Pretreated ◽  
Chemotherapy Agents ◽  
The Impact

Resistance to cancer chemotherapy is a common phenomenon especially in metastatic breast cancer (MBC), a setting in which patients typically have had exposure to multiple lines of prior therapy. The subsequent development of drug resistance can result in rapid disease progression during or shortly after completion of treatment. Moreover, cross-class multidrug resistance limits patient treatment choices, particularly in a setting where treatments options are few. One attempt to minimize the impact of drug resistance has been the concurrent use of two or more chemotherapy agents with unrelated mechanisms of action and differing modes of drug resistance, with the intent of blocking the development of multiple intracellular escape pathways essential for tumor survival. Within the past decade, an array of mechanistically diverse agents has augmented the list of combination regimens that may be both synergistic and efficacious in pretreated MBC. The aim of this paper is to review mechanisms of resistance to common chemotherapy agents and to consider current combination treatment options for heavily pretreated and/or drug-resistant patients with MBC.

scholarly journals Budgetary restrictions and ethical behaviours in a hospital context – evidence from general surgeons

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Cristina Piedade Silva ◽  
Rita Martins de Sousa
Keyword(s):  
Medical Profession ◽  
Participant Observation ◽  
Methodological Approach ◽  
Treatment Options ◽  
Patient Treatment ◽  
Ethical Behaviour ◽  
Content Type ◽  
Ethical Implications ◽  
General Surgeons ◽  
The Impact

Purpose The purpose of this paper is to study how budgetary constraints can have ethical implications on patient treatment options. Design/methodology/approach By applying a qualitative methodological approach (interviews) and participant observation, this paper studies the behaviour of surgeons in scenarios of financial restriction. Findings The empirical findings show that despite the conflict between the economy and the leges artis, surgeons maintain the ethical and deontological principles of their profession with fair rules of orientation. Practical implications The importance of this study can be realised by its continuity. One of the authors is already implicated on a wider research to investigate the influence of the economic scarcity of resources on general surgeons’ ethical behaviours. Social implications This paper is a contribution to understanding the rules that restrain the activities of surgeons. Politicians sometimes do not have a full understanding of the pressures that the medical profession faces in their day-to-day activities. Currently, with the addition of problems relate to COVID-19, politicians and populations seem to better understand the importance of the Serviço Nacional de Saúde (SNS), This paper hopes that this understanding will be not only a conjectural moment. Originality/value In conjunction with the economic recession that began in the first decade of this century, health institutions have long faced budgetary constraints that condition their material and human resources and correspondingly shape the scope of health professional activities. Until now, it has not been studied the impact of economic crises on the ethical behaviour of Portuguese surgeons. Therefore, this research is a first step and a useful contribution to understanding the rules that can restrain (or not) the ethical conduct of these health professionals.

scholarly journals Prospective Analysis of Patients with Metastatic Breast Cancer receiving Eribulin Mesylate as Second or More Lines of Chemotherapy: An Indian Experience

2018 ◽  
Vol 12 ◽  
pp. 117955491878247 ◽  
Author(s):  
BJ Srinivasa ◽  
Bhanu Prakash Lalkota ◽  
Girish Badarke ◽  
Diganta Hazarika ◽  
Nasiruddin Mohammad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Options ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Microtubule Inhibitor ◽  
Eribulin Mesylate ◽  
Primary Tumors ◽  
Free Survival ◽  
Heavily Pretreated

Background: Eribulin mesylate is a non-taxane microtubule inhibitor which can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of eribulin monotherapy in heavily pretreated patients with MBC. Methods: In this study, a total of 45 eligible patients with MBC who received eribulin in HCG Cancer Speciality Center from November 2014 to March 2016 were prospectively analyzed. Breslow (generalized Wilcoxon) survival analysis was carried out for progression-free survival and for overall survival. Patients were excluded if they had not taken treatment for 3 cycles and defaulted/expired during the treatment. Results: In this study, median age of patients was 52 years. A total of 27 (60%) patients had estrogen receptor and progesterone receptor (PR) positive primary tumors, whereas HER2 was overexpressed or amplified in 7 (15.6%); a triple negative subtype was recorded in 13 patients (28.9%). Regarding toxicity, 30 patients (66.67%) tolerated treatment well and 3 patients (6.67%) got anemia, 6 patients (13.3%) experienced neutropenia, and 7 (15.62%) patients had neurological toxicity. About 14 (31.1%) patients showed PR, 12 (26.7%) patients had stable disease (SD), whereas 19 (42.25%) patients showed progression disease (PD). Response evaluation at 6 cycles was possible in 18 patients and revealed that 4 (22.5%) patients showed PR, 10 (55.5%) patients had SD, whereas 4 (22.2%) patients had PD. Progression-free survival of the overall study population was 3.95 months. Conclusions: Eribulin mesylate is efficacious and tolerable chemotherapy as second- and third-line treatment options for MBC.

Impacts of toxicity on patient treatment choices for metastatic breast cancer.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 18-18 ◽  
Author(s):  
Carol B. White ◽  
Mary Lou Smith ◽  
Oyewale O. Abidoye ◽  
Deepa Lalla
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Online Survey ◽  
Metastatic Breast ◽  
Treatment Decisions ◽  
Subsequent Treatment ◽  
Patient Treatment ◽  
Treatment Choices ◽  
Almost All ◽  
The Impact

18 Background: Most patients with metastatic breast cancer (MBC) are treated with chemotherapy and/or targeted therapy with varying toxicity profiles. Experience with adverse events (AE) may vary and factor into subsequent treatment decisions. As newer agents and combinations become available, it becomes increasingly important to understand which AEs impact treatment decisions. Methods: The objective was to assess patient experience with AEs and preferences for future treatments. Following focus groups and pretests, an online survey was released by breast cancer organizations to recruit patients with MBC. The survey assessed the impact of experiences on future treatment choices and measured preferences via conjoint analysis (CA). Results: A total of 551 respondents completed the online survey. Among the AEs studied to assess their impact on either treatment stops or breaks, neutropenia topped the list, particularly for a required break. Fatigue, hand and foot syndrome, diarrhea, joint pain and peripheral neuropathy (PN) were high for chosen stops. Five AEs (fatigue, alopecia, diarrhea, PN, neutropenia) were studied extensively. Almost all respondents report experiencing fatigue, ~80% experienced alopecia, and ~66% each of the other 3 AEs. For each AE, the majority of respondents reported their prior experience would not impact a future decision involving the same AE; about 1/3 report they’d be more likely to take a treatment with the same AE; 8% to 18% would be less likely to take a treatment with the same AE. CA was also used to assess influence of the 5 AEs on future decisions. Within the tested ranges of likelihood, severity and duration, alopecia had the highest impact; PN, diarrhea, and neutropenia were in the middle; and fatigue was lowest. Further analysis is ongoing and final results will include differences in patient subgroups. Conclusions: This information informs priorities for development of new therapies allowing additional attention on AEs that matter most to patients. In addition, these results may generate discussion and consideration of patient preferences in conversations about care and treatment selection.

A simulation study of loss to follow up: The impact on time to event and prevention.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e14097-e14097
Author(s):  
Donna Elise Levy ◽  
Bingyan Wu ◽  
Daniel Quinn ◽  
Sophie Jentzsch ◽  
Christine Lusk ◽  
...  
Keyword(s):  
Treatment Options ◽  
Patient Treatment ◽  
Future Research ◽  
Time To Event ◽  
Loss To Follow Up ◽  
Study Results ◽  
Patient Attrition ◽  
The Impact ◽  
Future Patient

e14097 Background: Patient attrition during study follow up is a concern in all clinical trials, although its impact on study results has rarely been assessed. In oncology, in particular, where studies are lengthier and may be extended into longitudinal studies, there is an increased likelihood of loss to follow up (LTFU) (Gill et al., 2018). This creates a heightened need to understand how it affects the trial’s validity. The loss of data from patients who have been LTFU can reduce a study’s precision and power. This imprecision not only impacts the results of the current study but can also affect future research as well as future patient treatment options. Studies have found that participant characteristics differ in individuals LTFU as compared to those who remain in follow up (Childs et al., 2011; Geng et al., 2008; Hochheimer et al., 2016). This further emphasizes how attrition can skew study results and their interpretation and supports the need to minimize patient attrition during follow up in order to reduce bias and generate robust study estimates. Methods: This study assessed the impact of LTFU rates on the study estimates through simulations using SAS software. While all endpoints can be affected by LTFU, this study assessed time-to-event endpoints. Exponential distribution was assumed with varying rates of LTFU. In addition, the work covered suggestions for reducing LTFU. Results: Even for low rates of LTFU, biases are introduced in time-to event endpoints. Conclusions: Researchers should make every effort to minimize the extent of LTFU in the design and of and conduct of their trials.

Developing a prediction model for benefit from fulvestrant in heavily pretreated metastatic breast cancer (MBC) patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1041-1041
Author(s):  
E. Amir ◽  
O. C. Freedman ◽  
G. Dranitsaris ◽  
J. Napolskikh ◽  
S. Chia ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Prediction Model ◽  
Hormonal Therapy ◽  
Metastatic Breast ◽  
Retrospective Chart Review ◽  
Older Age ◽  
Adjuvant Hormonal Therapy ◽  
Data Set ◽  
Prior Therapy ◽  
Heavily Pretreated

1041 Background: Fulvestrant use in heavily pretreated patients with MBC is associated with highly variable responses. This study aimed to characterize the benefit of fulvestrant therapy and develop a prediction model for clinical benefit in this setting. Methods: A nationwide, retrospective chart review of patients enrolled in a Canadian compassionate use program was performed. This program mandated prior therapy with tamoxifen and both steroidal and non-steroidal aromatase inhibitors. Charts from the seven highest accruing centers were reviewed. Sample size was based on the derivation of a model to predict the probability of a patient remaining on fulvestrant and free from chemotherapy for at least 3 months. Results: 305 women received at least one dose of fulvestrant; 207 went on to receive chemotherapy (68%). Of these, 48 (23%) required chemotherapy at 3 months, 113 (55%) at 6 months, and 170 (82%) by 12 months. Median duration of fulvestrant treatment was 126 days (range 23–1920). Median overall survival from start of fulvestrant was 698 days (25th percentile 316 days-75th percentile 1,359 days). The preliminary prediction model showed that older age (OR 0.96, 95% CI 0.93–0.99) and having received no adjuvant hormonal therapy (OR 0.5, 95% CI 0.2–1.25) predicted a greater chance of remaining chemotherapy-free at 3 months. Presence of lung (OR 2.55, 95% CI 1.1–5.9) or brain metastases (OR12.8, 95% CI 4.1–55.4) predicted a lower chance of remaining chemotherapy-free at 3 months. Conclusions: Older age and having received no prior adjuvant hormonal therapy predicted a greater chance of remaining chemotherapy free at 3 months, while lung and brain metastases predicted a lower chance. These factors will be validated in an international data set, and may be considered when prescribing fulvestrant. A 6-month prediction model is currently under development. [Table: see text]

scholarly journals Therapeutic Considerations for Docetaxel and Paclitaxel in Metastatic Breast Cancer

2020 ◽  
Vol 10 (1-s) ◽  
pp. 196-204
Author(s):  
Doranala Harshini ◽  
Sreenivas Pasula ◽  
Vesangi Keerthi Vaishnavi ◽  
Shiva Sai Tekula ◽  
M. Rajendar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Cancer ◽  
Treatment Options ◽  
Single Agent ◽  
Metastatic Breast ◽  
Complete Response ◽  
Heavily Pretreated ◽  
Combination Regimens ◽  
Refractory Diseases

Breast cancer is the main source of death among women. Currently, 77% of women diagnosed with breast cancer are age 50 and older; however, it is projected that approximately 66% of the new cases diagnosed will occur in women younger than 65. Several clinical trials have assessed the wellbeing and adequacy of taxanes along with their tolerability in patients with metastatic cancer (MBC) The overview of these Paclitaxel and Docetaxel, the mechanism of action, pharmacokinetics and pharmacodynamics, dose and administration, adverse effects, clinical potency, and sufferable profiles combination therapies, the pathological complete response of these taxanes are included. The different novel formulations of taxanes are formulated from nanoparticles, polyglutamate, liposomes to improve the wellbeing and adequacy taxanes to reduce their toxicities. Single-agent research located with docetaxel and paclitaxel in metastatic breast most cancers show clinically huge antitumor motion even in the advanced stage, heavily pretreated, safe, as properly as in refractory diseases. This action is likewise clear with taxane-based combination regimens. Serious hematologic and nonhematologic toxicities are incompatible, with different toxicities noted dependent on the portion and weekly regimen selected.  Weekly docetaxel and paclitaxel regimens speak to important helpful treatment options for women suffering from metastatic breast cancer and have entered assessment as a major aspect of adjuvant treatment for this disease Toxicity associated with taxanes chemotherapy are based totally on the dose schedules and weekly regimen selected and the most frequent toxicities related with these marketers include myalgia, peripheral neuropathy, neutropenia, etc Docetaxel retains in tumor cells for longer duration when compared to paclitaxel because of its slow efflux and large amounts of uptake into the cell which explains its more benefits when compared to paclitaxel. Clinical studies conducted so far suggested a more benefit to risk ratio for docetaxel when compared to paclitaxel. This article reviews mainly different actions exhibited by taxanes in the therapy of metastatic breast cancer and others on stages of cancer along with the toxicities associated with these agents.  

scholarly journals Chemotherapy Options beyond the First Line in HER-Negative Metastatic Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Vito Lorusso ◽  
Agnese Latorre ◽  
Francesco Giotta
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
First Line ◽  
First Line Therapy ◽  
Heavily Pretreated ◽  
Literature Evidence ◽  
Antimicrotubule Agents ◽  
Chemotherapy Agents

Despite the recent advances in the biological understanding of breast cancer (BC), chemotherapy still represents a key component in the armamentarium for this disease. Different agents are available as mono-chemotherapy options in patients with locally advanced or metastatic BC (MBC) who progress after a first- and second-line treatment with anthracyclines and taxanes. However, no clear indication exists on what the best option is in some populations, such as heavily pretreated, elderly patients, triple-negative BC (TNBC), and those who do not respond to the first-line therapy. In this article, we summarize available literature evidence on different chemotherapy agents used beyond the first-line, in locally advanced or MBC patients, including rechallenge with anthracyclines and taxanes, antimetabolite and antimicrotubule agents, such as vinorelbine, capecitabine, eribulin, ixabepilone, and the newest developed agents, such as vinflunine, irinotecan, and etirinotecan.

scholarly journals Improving the effectiveness of cancer multidisciplinary team meetings: analysis of a national survey of MDT members’ opinions about streamlining patient discussions

2019 ◽  
Vol 8 (2) ◽  
pp. e000631 ◽  
Author(s):  
Linda Hoinville ◽  
Cath Taylor ◽  
Magda Zasada ◽  
Ross Warner ◽  
Emma Pottle ◽  
...  
Keyword(s):  
Patient Care ◽  
National Survey ◽  
Treatment Options ◽  
Secondary Analysis ◽  
Patient Treatment ◽  
Multidisciplinary Teams ◽  
Quality And Safety ◽  
Treatment Protocols ◽  
The Uk ◽  
The Impact

BackgroundCancer is diagnosed and managed by multidisciplinary teams (MDTs) in the UK and worldwide, these teams meet regularly in MDT meetings (MDMs) to discuss individual patient treatment options. Rising cancer incidence and increasing case complexity have increased pressure on MDMs. Streamlining discussions has been suggested as a way to enhance efficiency and to ensure high-quality discussion of complex cases.MethodsSecondary analysis of quantitative and qualitative data from a national survey of 1220 MDT members regarding their views about streamlining MDM discussions.ResultsThe majority of participants agreed that streamlining discussions may be beneficial although variable interpretations of ‘streamlining’ were apparent. Agreement levels varied significantly by tumour type and occupational group. The main reason for opposing streamlining were concerns about the possible impact on the quality and safety of patient care. Participants suggested a range of alternative approaches for improving efficiency in MDMs in addition to the use of treatment protocols and pre-MDT meetings.ConclusionsThis work complements previous analyses in supporting the development of tumour-specific guidance for streamlining MDM discussions considering a range of approaches. The information provided about the variation in opinions between MDT for different tumour types will inform the development of these guidelines. The evidence for variation in opinions between those in different occupational groups and the reasons underlying these opinions will facilitate their implementation. The impact of any changes in MDM practices on the quality and safety of patient care requires evaluation.

Phase III trial of ixabepilone plus capecitabine compared to capecitabine alone in patients with metastatic breast cancer (MBC) previously treated or resistant to an anthracycline and resistant to taxanes

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1006-1006 ◽  
Author(s):  
L. T. Vahdat ◽  
E. Thomas ◽  
R. Li ◽  
J. Jassem ◽  
H. Gomez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Objective Response ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Phase Iii Trial ◽  
Hand Foot Syndrome ◽  
Heavily Pretreated

1006 Background: Patients with MBC who have progressed after anthracyclines and taxanes have limited treatment options. Ixabepilone, a novel epothilone B analog, is active in resistant breast cancer. Methods: In this large multinational phase III trial, patients with MBC who were anthracycline pretreated and met predefined resistance criteria to taxanes were randomized to ixabepilone (40mg/m2 IV over 3h Q3w) + capecitabine (1,000mg/m2 PO BID Q14d) or capecitabine (1,250mg/m2 PO BID Q14d). The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), safety, and overall survival (available after 2007). Response and progression were assessed by an independent review committee (IRC) and the investigators (INV). Results: 752 patients were randomized. Median age was 53; 84% had visceral disease, 48% and 43% had 1 and =2 prior metastatic regimens. Median of 5 and 4 cycles of ixabepilone + capecitabine and capecitabine were administered. Ixabepilone + capecitabine was superior to capecitabine. Significant benefit was consistently maintained across predefined subgroups, including HER2-/ER- /PR- and HER2+. *Primary analysis of PFS; hazard ratio= 0.75. Grade (G) 3/4 adverse events included neuropathy (ixabepilone + capecitabine 23% vs capecitabine 0%), hand-foot syndrome (18% vs 17%), and fatigue (9% vs 3%). Neuropathy was cumulative and reversible (median time to resolution of G3/4 to baseline/G1 was 6 weeks). G3 and 4 neutropenia were reported in 32% and 36% vs 9% and 2%, respectively; febrile neutropenia was 5% with ixabepilone + capecitabine. Toxic death rate was 3% vs 1%. Patients with liver dysfunction were at greater risk. Conclusions: Ixabepilone + capecitabine has superior efficacy to capecitabine across endpoints and has a manageable safety profile in this heavily pretreated population. It offers a new potential option for patients with MBC. [Table: see text] No significant financial relationships to disclose.

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