Sasha Mazzarello

Preference weights for chemotherapy side effects from the perspective of women with breast cancer

AbstractnPerceptions among women with breast cancer about the relative importance of different potential chemotherapy side effects is not well understood. A survey was performed by women receiving chemotherapy for breast cancer. Grade I/II (mild to moderate) and III/IV (moderate to severe) descriptions of nine common chemotherapy side effects were assigned preference weights using the standard gamble technique. For each hypothetical side effect, patients could choose to stay in the respective side effect state or take a gamble between full health (probability p) or being dead (1xa0−xa0p). For each side effect, p was varied until the patient was indifferent between these options. The survey also included questions about the importance of survival, slowing cancer growth, and quality of life. This analysis included 69 patients; mean age 54xa0years (range 35–84), representing all cancer stages. Standard gamble preferences were lowest (i.e., least preferred) for grade III/IV nausea/vomiting (0.621), indicating that patients would, on average, risk a 38xa0% chance of being dead to avoid having grade III/IV nausea/vomiting for the rest of their lives. The next least preferred side effects were grade III/IV diarrhea (0.677) and grade III/IV sensory neuropathy (0.694). Survival appeared more important than slowing cancer growth and maintaining quality of life across cancer stages. Nevertheless, patients with advanced disease placed less importance on survival (pxa0=xa00.09) and higher importance on quality of life (pxa0=xa00.05). These standard gamble utilities provide unique insights into chemotherapy toxicities from the patient perspective. Differences in the relative importance of overall survival and quality of life with treatment existed between patients with different stages of disease. These studies should be expanded as the data may also be used to calculate quality-adjusted life expectancy in cost-effectiveness evaluations of breast cancer chemotherapies.

A phase II, multicentre trial evaluating the efficacy of de-escalated bisphosphonate therapy in metastatic breast cancer patients at low-risk of skeletal-related events

Abstract The optimal frequency of intravenous (IV) bisphosphonate administration is unclear. We thus performed a study evaluating the effects of switching from 3–4 to 12 weekly therapy in patients with biochemically defined low-risk bone metastases. Patients with serum C-telopeptide (CTx) levels ≤600xa0ng/L after ≥3xa0months of 3–4 weekly IV pamidronate were switched to 12 weekly therapy for 48xa0weeks. Primary endpoint was the proportion of patients maintaining CTx levels in the lower-risk range. All endpoints (serum CTx and bone-specific alkaline phosphatase (BSAP), skeletal-related events (SREs) and self-reported pain) were measured at baseline, 6, 12, 24, 36 and 48xa0weeks. Treatment failure was defined as biochemical failure (CTxxa0>xa0600xa0ng/L) or a SRE. Exploratory biomarkers including; serum TGF-β, activin-A, bone sialoprotein (BSP), procollagen type 1 N-terminal propeptide and urinary N-telopeptide (NTx) were assessed at baseline as predictors for failure to complete treatment. Seventy-one patients accrued and 43 (61xa0%) completed 48xa0weeks of de-escalated therapy. Reasons for failure to complete treatment included; biochemical failure (CTxxa0>xa0600xa0ng/L) (nxa0=xa010, 14.1xa0%), on-study SRE (nxa0=xa09, 12.7xa0%), disease progression (nxa0=xa07, 9.9xa0% including death from disease [nxa0=xa01, 1.4xa0%]) or patient choice (nxa0=xa02, 2.8xa0%). Elevated baseline levels of CTx, BSAP, NTx and BSP were associated with treatment failure. The majority of patients in this biochemically defined low-risk population could switch from 3–4 weekly to 12 weekly bisphosphonate therapy with no effect on CTx levels or SREs during the 48xa0week study. Larger trials are required to assess the roles of biomarkers as predictors of adequacy of de-escalated therapy.

Oral care and the use of bone-targeted agents in patients with metastatic cancers: A practical guide for dental surgeons and oncologists

Background Bone-targeted agents such as bisphosphonates and the RANKL antibody have revolutionised the care of patients with bone metastases. There has, however been increasing concern about the oral health of these patients and in particular osteonecrosis of the jaw (ONJ), especially with the increasing use of these agents at higher potencies for greater periods of time. Methods A review of the published data in PubMed and meeting abstracts was performed to examine incidence, risk factors, pathogenesis, clinical course and management of osteonecrosis of the jaw with focus on cancer patients treated with bone-targeted agents (BTA) for bone metastases. This manuscript takes the most frequent and pertinent questions raised by oncologists, dentists and oral and maxillofacial surgeons and tries to give a pragmatic overview of the literature. Results The incidence of ONJ varies depending on types of bone-targeted agents, duration of treatment and additional risk factors. The causes and pathogenesis of ONJ is not fully elucidated, however bone-targeted therapy induced impaired bone remodelling, microtrauma secondary to jaw activity, and oral bacterial infection seem to be important factors. Since the treatment options for ONJ are limited and not well established, preventive strategies have to be included in patients management. Conclusions Many unanswered questions remain about the optimal oral care of patients receiving bone-targeted agents. Prospective data collection will remedy this and help to provide practical guidelines for the management and treatment of those patients that require dental intervention.

De-escalated administration of bone-targeted agents in patients with breast and prostate cancer-A survey of Canadian oncologists.

Objective Questions remain regarding the optimal use of bone-targeted agents in patients with metastatic bone disease. The purpose of this study was to assess current clinical practice regarding the use and administration of bone-targeted agents by Canadian oncologists in patients with metastatic breast and prostate cancer. Methods A survey was designed to explore; bone-targeted agent use in metastatic bone disease, variability in the choice and the frequency of administration of these agents. Opinions were sought on potential outcomes for future trials. Results A total of 193 clinicians were contacted and 90 completed our survey (response rate 49% after adjustment for inactivity). Survey respondents were medical oncologists (71.1%), radiation oncologists (21.1%) and urologists (7.8%). The findings suggest that once bone-targeted agents are started they are rarely discontinued. More agents are used in breast cancer than in prostate cancer. There was considerable interest in performing studies of de-escalated therapy in both breast and prostate cancer. Physicians requested (86%) that the primary study endpoint be the occurrence of skeletal related events and not biomarker driven. Conclusions Despite clinical practice guidelines and widespread use, significant areas of clinical equipoise with respect to use of bone-targeted agents exist. Findings from this survey suggest that physicians are interested in de-escalated therapy for both breast and prostate patients. However, the use of multiple agents in breast cancer and the desire for skeletal related events to be the primary endpoint means that very large randomized studies will be required.

Optimisation of steroid prophylaxis schedules in breast cancer patients receiving docetaxel chemotherapy—a survey of health care providers and patients

PurposeDespite the widespread use of steroid prophylaxis schedules for breast cancer patients receiving docetaxel chemotherapy, questions still exist regarding their optimal use. We surveyed health care providers and patients about their experiences with steroid prophylaxis.MethodsTwo questionnaires were developed and circulated. One was presented to health care providers (chemotherapy nurses, pharmacists and medical oncologists) involved in the treatment of breast cancer and the second to patients who had received docetaxel chemotherapy for early stage breast cancer.ResultsThe health care providers’ questionnaire was completed by 184 of 698 invitees: 92/171 (53.8xa0%) chemotherapy nurses, 56/284 (19.7xa0%) pharmacists and 36/243 (14.8xa0%) medical oncologists (overall response rate 26.4xa0%). Two steroid schedules were found to be the most commonly used: dexamethasone 8xa0mg BID for 6 doses, with either 3 (79xa0%) or 2 (11xa0%) doses taken before docetaxel administration. Suboptimal adherence to steroid premedication had been experienced by 98xa0% (177/181) of practitioners. Despite the presence of local treatment protocols in 65xa0% (119/183) of practitioners’ institutions, 10 different strategies were commonly used when steroid premedication was taken incorrectly. The patients’ questionnaire was completed by 72/87 (82.3xa0%) invitees. Respondents reported correctly taking their premedication 99xa0% (70/71) of the time. Patients felt steroids frequently caused side effects, the most common being sleep disturbance (35/72u2009=u200949xa0%) and skin toxicity (16/72u2009=u200922xa0%).ConclusionSuboptimal adherence to steroid premedication prior to docetaxel administration is a common clinical challenge. There appears to be discordance between the practitioner and the patient experience. A single, universally accepted and used protocol for both pre- and post-medication and management when premedication is not taken as prescribed could improve adherence.

Bone-targeted agent use for bone metastases from breast cancer and prostate cancer: A patient survey.

Background In order to design studies assessing the optimal use of bone-targeted agents (BTAs) patient input is clearly desirable. Methods Patients who were receiving a BTA for metastatic prostate or breast cancer were surveyed at two Canadian cancer centres. Statistical analysis of respondent data was performed to establish relevant proportions of patient responses. Results Responses were received from 141 patients, 76 (53.9%) with prostate cancer and 65 (46.1%) with breast cancer. Duration of BTA use was <3 months (15.9%) to >24 months (35.2%). Patients were uncertain how long they would remain on a BTA. While most felt their BTA was given to reduce the chance of bone fractures (77%), 52% thought it would slow tumour growth. Prostate patients were more likely to receive denosumab and breast cancer patients, pamidronate. There was more variability in the dosing interval for breast cancer patients. Given a choice, most patients (49–57%) would prefer injection therapy to oral therapy (21–23%). Most patients (58–64%) were interested in enrolling in clinical trials of de-escalated therapy. Conclusion While there were clear differences in the types of BTAs patients received, our survey showed similarity for both prostate and breast cancer patients with respect to their perceptions of the goals of therapy. Patients were interested in participating in trials of de-escalated therapy. However, given that patients receive a range of agents for varying periods of time and in different locations (e.g. hospital vs. home), the design of future trials will need to be pragmatic to reflect this.

A randomized, double-blind, phase II, exploratory trial evaluating the palliative benefit of either continuing pamidronate or switching to zoledronic acid in patients with high-risk bone metastases from breast cancer

Previous studies suggest switching from pamidronate to a more potent bone-targeted agent is associated with biomarker and palliative response in breast cancer patients with bone metastases. Until now, this has not been addressed in a double-blind, randomized trial. Breast cancer patients with high-risk bone metastases, despite >3xa0months of pamidronate, were randomized to either continue pamidronate or switch to zoledronic acid every 4xa0weeks for 12xa0weeks. Primary outcome was the proportion of patients achieving a fall in serum C-telopeptide (sCTx) at 12xa0weeks. Secondary outcomes included difference in mean sCTx, pain scores, quality of life, toxicity, and skeletal-related events (SREs). Seventy-three patients entered the study; median age 61xa0years (range 37–87). Proportion of patients achieving a fall in sCTx over the 12-week evaluation period was 26/32 (81xa0%) with zoledronic acid and 18/29 (62xa0%) with pamidronate (pxa0=xa00.095). Mean decrease in sCTx (mean difference between groupsxa0=xa050xa0ng/L, 95xa0% CI 18–84; pxa0=xa00.003) was significantly greater in patients who received zoledronic acid. Quality of life, pain scores, toxicity, and frequency of new SREs were comparable between the two arms. While a switch from pamidronate to zoledronic acid resulted in reduction in mean sCTx, there were no significant differences between the arms for proportion of patients achieving a reduction in sCTx, quality of life, pain scores, toxicity or SREs. Given the lack of palliative improvement, the current data do not support a switching strategy.

Publishing clinical research: ten pearls for oncology trainees and junior oncologists

The old adage of “publish or perish” bears some truth. As the lines between “academic” and “community” practice blur, more physicians are expected to participate in “scholarly activities.” Such activities will be required regardless of career path in clinical care, education, research, or administration. A successful research project can set oncology hopefuls apart from other applicants and can drive conversations at interviews. Research can also provide opportunities to attend conferences, where networking with other researchers is critical to one’s work and general career development. For oncologists, peer-reviewed publications are an objective indicator of productivity, an important component of annual assessments, and an integral component of university promotion processes. n nAlthough research is not for everyone, seeing a project through to peer-reviewed publication carries great merit because of the effort and persistence it requires. Previous publications have outlined how to conduct research1,2 and the importance of having a good mentor3–6. We hope that the present article, with its 10 pragmatic tips, will help junior researchers ultimately to publish their work. Although not every point is supported by a peer-reviewed publication (or at times by specific evidence), our tips are derived from conversations with other researchers and from our own experiences with editing, publishing, and (we must admit) countless rejections. As authors, we reflect all stages of training—university graduate (SM), resident (MF), research fellow (CJ), junior faculty (AA), and old-timer (MC)—and we hope that the “pearls,” while not telling the whole story, will at least provoke lively debate.

A cost-utility analysis of risk model-guided versus physician’s choice antiemetic prophylaxis in patients receiving chemotherapy for early-stage breast cancer: a net benefit regression approach

PurposeWe assessed the cost-effectiveness of a risk model-guided (RMG) antiemetic prophylaxis strategy compared with the physician’s choice (PC) strategy in patients receiving chemotherapy for early-stage breast cancer.MethodsWe conducted a cost-utility analysis based on a published randomized controlled trial of 324 patients with early-stage breast cancer undergoing chemotherapy at two Canadian cancer centers. Patients were randomized to receive their antiemetic treatments according to either predefined risk scores or the treating physician’s preference. Effectiveness was measured as quality-adjusted life years (QALYs) gained. Cost and utility data were obtained from the Canadian published literature. We used generalized estimating equations to estimate the incremental cost-effectiveness ratios (ICERs) and 95% confidence intervals (CIs) over a range of willingness-to-pay values. The lower and upper bounds of the 95% CIs were used to characterize the statistical uncertainty for the cost-effectiveness estimates and construct cost-effectiveness acceptability curves.ResultsFrom the health care system’s perspective, the RMG strategy was associated with greater QALYs gained (0.0016, 95% CI 0.0009, 0.0022) and higher cost (

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49.19, 95% CI