Polypharmacy and the use of low or limited value medications in advanced cancer.

BACKGROUND: Patients with advanced malignancy are often on medications for co-morbidities, including those for primary or secondary prevention. The benefit from these medications can be limited and may result in adverse effects, interact with medications used for the malignancy or associated symptoms, increase pill burden and reduce quality of life. AIMS: To evaluate the proportion of patients with advanced malignancy that were continued on low or limited value medications and identify the factors associated with this. We also sought to determine how prevalent polypharmacy was within this group of patients and the factors associated with this. METHODS: A retrospective chart review was conducted of patients with incurable malignancy admitted under medical oncology at Liverpool Hospital over a 90-day period. Demographic variables, co-morbidities, disease related parameters and medications were reviewed. Criteria were established to identify low or limited value medications. RESULTS: Seventy-eight patients were identified between September and December 2018. Thirty-day mortality was 33%. Sixty-five percent of the cohort was on five or more medications and 24% on 10 or more. One low or limited value medication was reported in 36% and 20% were on two or more. Age ≤60 years was associated with a risk of being on at least one unnecessary medication. Patients with fewer co-morbidities and those in their last 3 months of life were significantly less likely to have polypharmacy. Nine percent of the cohort was on three or more antihypertensives and 6% of patients were on three or more oral hypoglycaemics. CONCLUSION: Polypharmacy and continued prescribing of low or limited value medications was identified in a high proportion of patients. Further studies are needed to assess the impact of continuing these medications, as well as investigation of patient and physician attitudes towards de-escalation.

Association between ribociclib and changes in creatinine in patients with hormone receptor positive metastatic breast cancer.

Combination ribociclib and aromatase inhibitors are currently the preferred treatment in Australia for newly diagnosed hormone receptor positive metastatic breast cancer in the absence of visceral crisis. In our case series of 32 patients, 28% experienced grade 1 elevations in creatinine, a toxicity that was under-recognised in large phase III studies. Creatinine rise appears to be due to a reversible inhibition of renal efflux transporters rather than an acute kidney injury in the majority of cases.

Risk of emergency hospitalisation and survival outcomes following adjuvant chemotherapy for early breast cancer in New South Wales, Australia.

OBJECTIVE: To examine risk of emergency hospital admission and survival following adjuvant chemotherapy for early breast cancer. METHODS: Linked data from New South Wales population-based and clinical cancer registries (2008-2012), hospital admissions, official death records and pharmaceutical benefit claims. Women aged ≥18 years receiving adjuvant chemotherapy for early-stage operable breast cancer in NSW public hospitals were included. Odds ratios (OR) for emergency hospitalisation within 6 months following chemotherapy initiation were estimated using logistic regression and survival using Kaplan-Meier and Cox proportional hazards methods. RESULTS: A total of 3,950 women were included and 30.6% were hospitalised. The most common principal diagnosis at admission was neutropenia (30.8%). Women receiving docetaxel/carboplatin/trastuzumab (TCH) and docetaxel/cyclophosphamide (TC) were the most frequently hospitalised. After adjustment for demographic and clinical factors, the increased risk of hospitalisation for TCH and TC remained compared with doxorubicin/cyclophosphamide 3-weekly (OR 1.71, 95% confidence interval [CI] 1.24-2.37 and OR 1.47, 95% CI 1.17-1.85 respectively). Five-year overall survival was similar for women who were (92.2%, 95% CI 90.7-93.8) and were not hospitalised (93.1%, 95% CI 92.1-94.1). CONCLUSION: Emergency hospitalisations following chemotherapy for early breast cancer were relatively common, especially following docetaxel-containing protocols. Further examination of reasons for admission is needed to inform actions to improve patient safety.

Patterns of care and outcomes among triple-negative early breast cancer patients in South Western Sydney.

BACKGROUND: Triple-negative breast cancer (TNBC) represents 12-24% of all breast cancer and carries a poor prognosis upon recurrence. Little is known of the treatment, or timing and frequency of recurrences outside of a clinical trial. AIM: We describe the patterns of care and outcomes of women with TNBC treated at two cancer centres in Sydney, NSW, Australia, to help oncologists talk to women with this subtype of breast cancer about their likely prognosis. METHODS: We searched the electronic medical record for women with stages I-III TNBC diagnosed from 2006 to 2014. For each woman, we recorded demographics, tumour characteristics, treatment details, recurrences and survival using the Kaplan-Meier method. RESULTS: We identified 137 women with a median age of 55 years (interquartile range (IQR) 44-63). The median tumour size was 25 mm (IQR 16-35). Most women had grade 3 (92%) and ductal carcinomas (89%), and 35% were node positive; 113 (82%) patients received (neo)adjuvant chemotherapy. The most prescribed regimens for node-negative tumours were: fluorouracil, epirubicin and cyclophosphamide (FEC) × 6 (23pts, 35%), and for node-positive tumours, FEC-Docetaxel (18pts, 40%). Adjuvant radiotherapy was delivered to 114 (83%) patients. After a median follow up of 40 months, 17 patients (12%) had a recurrence. All but one recurrence (94%) occurred within 3 years of diagnosis. Twelve women received palliative chemotherapy, and 14 women have died. The median survival from the time of recurrence was 18 months (IQR 5-26). Seven women (5%) had a documented BRCA1 mutation, and four women (3%) had a documented BRCA2 mutation. CONCLUSIONS: TNBC affects women at a relatively young age and tends to recur early. Survival following metastatic disease is short, and more effective therapies are needed.

Baduanjin Mind-Body Exercise for Cancer-Related Fatigue: Protocol for a Remotely Delivered Randomized Wait-List Controlled Feasibility Study.

BACKGROUND: People living with a cancer diagnosis often experience cancer-related fatigue (CRF). Between 9% and 45% of people report CRF as moderate to severe, negatively impacting their quality-of-life (QOL). The evidence-base for managing CRF recommends exercise-related therapies over pharmaceutical interventions. One such exercise-like therapy is Baduanjin mind-body exercise (MBE), which has additional benefits. A remotely delivered program may further benefit people with CRF. The primary objective of this pilot will test study feasibility of a remotely delivered Baduanjin MBE exercise program for people living with CRF. METHODS: This is a randomized wait-list controlled pilot study and will take place in Sydney, Australia. Subject to informed consent, 40 adults with moderate CRF levels and receiving or previously received adjuvant chemotherapy, will undertake a home-based 8-week Baduanjin MBE program supported by online resources and instructors. The primary feasibility outcomes are recruitment, enrollment, retention, and adherence rates; and safety as measured by tolerance and adverse-event frequency. Clinical outcomes (eg, changes in CRF, QOL, and participant perceptions) are assessed at pre-intervention, week 1, week 4, week 8, and post-intervention. Analyses follows the Intent-to-Treat (all participants as per randomization) and per-protocol (participants adhering to the protocol). Missing data will be imputed from previous data entries and regression models may be tested to predict missing outcomes. DISCUSSION: To our knowledge, this is the first study evaluating the feasibility and effects of Baduanjin MBE on CRF using a remote delivery method. These feasibility data will inform a fully powered future trial investigating evidence of effect on CRF and QOL.Trial registration: Australian and New Zealand Clinical Trials Registry (ANZCTR 12623000177651).Ringgold ID: 651498 Chinese Medicine Centre.

A Phase 1 Proof of Concept Study Evaluating the Addition of an LSD1 Inhibitor to Nab-Paclitaxel in Advanced or Metastatic Breast Cancer (EPI-PRIMED).

Objective: Lysine-Specific Demethylase-1 (LSD1) is overexpressed in breast cancer cells and facilitate mesenchymal properties which may contribute to therapeutic resistance and cancer progression. The purpose of this study was to investigate the safety of combination, nab-paclitaxel and phenelzine, an irreversible LSD1 inhibitor in patients with metastatic breast cancer (mBC). Methods: Eligible patients with mBC were treated with nab-paclitaxel (100mg/m2) weekly for 3 weeks with one week break in a 28-day cycle. Dose escalation of phenelzine followed the Cumulative Cohort Design and phenelzine treatment commenced from day 2 of first cycle. Eleven patients were screened, and eligible patients were enrolled in cohorts with the dose of phenelzine ranging from 45mg to 90mg. Results: The Optimum Biological Dose was established at 60mg of phenelzine daily in combination with nab-paclitaxel and considered as the recommended phase 2 dose. Most (95%) of adverse events were grade 1 or 2 with two grade 3 events being diarrhea and neutropenia at 45mg and 60mg phenelzine respectively, with no unexpected toxicity/deaths. Commonly reported toxicities were fatigue (n=4,50%), dizziness (n=6,75%), neutropenia (n=3,37.5%), peripheral neuropathy (n=3,37.5%), diarrhea (n=2,25%), and hallucination (n=2,25%). After a median follow up of 113 weeks, all patients showed disease progression on trial with 4 patients being alive at the time of data cut off, including one patient with triple negative breast cancer. Median progression-free survival was 34 weeks. Significant inhibition of LSD1 and suppression of mesenchymal markers in circulating tumor cells were noted. Conclusion: Phenelzine in combination with nab-paclitaxel was well tolerated, without any unexpected toxicities in patients with mBC and demonstrated evidence of antitumor activity. For the first time, this proof-of-concept study showed in-vivo inhibition of LSD1 suppressed mesenchymal markers, which are known to facilitate generation of cancer stem cells with metastatic potential. Clinical Trial Registration: ClinicalTrials.Gov NCT03505528, UTN of U1111-1197-5518.

Concurrent Paraneoplastic Dermatomyositis and Acquired C1 Esterase Inhibitor Deficiency in Primary Laryngeal Small Cell Carcinoma.

Small cell carcinoma is associated with a number of paraneoplastic syndromes. We report a case of a 42-year-old female who presented with primary laryngeal small cell carcinoma associated with concurrent paraneoplastic dermatomyositis and paraneoplastic angioedema secondary to acquired C1 esterase inhibitor deficiency. The patient required extensive treatment for her dermatomyositis including high-dose corticosteroid therapy and intravenous immunoglobulin followed by steroid-sparing disease-modifying immunosuppression. Her angioedema also required multiple lines of therapy including bradykinin inhibitors and human recombinant C1 esterase. We believe this is the first reported case of either of these paraneoplastic syndromes arising from an extrapulmonary small cell carcinoma and highlights the difficulty of its initial diagnosis as well as concurrent management.

Survival and cardiac toxicity in patients with HER2-positive, metastatic breast cancer treated with trastuzumab in routine clinical practice.

AIMS: We sought to describe survival outcomes and toxicities of trastuzumab in real-world patients with HER2-positive, metastatic breast cancer (MBC) and compare these to a recent systematic review of clinical trials. METHODS: We searched the medical records of three Sydney cancer centers for patients with HER2-positive, MBC starting trastuzumab from January 2001 to March 2017. We recorded patient, tumor, and treatment characteristics; survival times from start of palliative trastuzumab; and rates of cardiac toxicity. Survival distribution was summarized using the following percentiles (represented scenario): 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). Survival times were compared to recent review of HER2-positive MBC randomized trials. Factors associated with survival were assessed with Cox models. RESULTS: Characteristics of the 126 patients were: median age 53 years, ER positive cancer (50%), de-novo metastatic disease (23%), prior adjuvant trastuzumab (15%), liver metastases (37%), and brain metastases (23%). The median duration of first-line trastuzumab was 11 months (interquartile range, (IQR) 5-27). Survival times in months (vs the systematic review) were: 90th percentile 8 (9); 75th percentile 16 (19); and median 34 (33). Follow-up duration was insufficient to estimate the 25th and 10th percentiles, similar to the systematic review. Liver metastases were associated with shorter survival (HR = 1.74, 95% CI, 1.1-2.76, P = .02). Seventy percent of patients had a baseline cardiac assessment. Five patients (3.9%) developed symptomatic cardiac toxicity, similar to clinical trials. CONCLUSION: Survival and cardiac toxicity rates for women starting trastuzumab in routine practice were comparable to clinical trials. Oncologists can use clinical trial data as a reference point when explaining survival outcomes to women with HER2-positive MBC.

Acupuncture for Cancer Related Pain: Protocol for a Pragmatic Randomised Wait-List Controlled Trial.

BACKGROUND: Acupuncture has been proved effective for cancer related pain (CRP) in China, America and some other countries. However, there is relative lack of evidence to support the use of acupuncture for CRP in Australia. OBJECTIVES: To assess the effectiveness and safety of acupuncture for management of CRP in a real-world setting and to understand cancer patients' experience of undergoing acupuncture for CRP. METHODS: A pragmatic randomised controlled trial will be conducted in South Western Sydney Local Health District (SWSLHD) in NSW, Australia. Adults with cancer related pain (n = 106) will be randomised in a 1:1 ratio to receive the acupuncture intervention up front versus after a wait list period of 4 weeks. Pain level (by Numerical Rating Scale), analgesic use, auricular acupressure frequency and adverse events will be assessed at baseline, mid-treatment and post-treatment. Expectancy on trial outcome (by Credibility and Expectancy questionnaire) will be assessed at baseline. The perspective of the participants (by an interview) will be recorded after the last intervention. EXPECTED OUTCOMES: We hypothesise that acupuncture will relieve cancer related pain at mid-treatment and post-treatment. We also hypothesise that few adverse events will be provoked by acupuncture. TRIAL REGISTRATION: Australia New-Zealand Clinical Trial Registry (ACTRN12620000325909).

Herbal Medicine for Hot Flushes Induced by Endocrine Therapy in Women with Breast Cancer: A Systematic Review and Meta-Analysis.

Objective. This systematic review was conducted to evaluate the clinical effectiveness and safety of herbal medicine (HM) as an alternative management for hot flushes induced by endocrine therapy in breast cancer patients. Methods. Key English and Chinese language databases were searched from inception to July 2015. Randomized Controlled Trials (RCTs) evaluating the effects of HM on hot flushes induced by endocrine therapy in women with breast cancer were retrieved. We conducted data collection and analysis in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was performed with the software (Review Manager 5.3). Results. 19 articles were selected from the articles retrieved, and 5 articles met the inclusion criteria for analysis. Some included individual studies showed that HM can relieve hot flushes as well as other menopausal symptoms induced by endocrine therapy among women with breast cancer and improve the quality of life. There are minor side effects related to HM which are well tolerated. Conclusion. Given the small number of included studies and relatively poor methodological quality, there is insufficient evidence to draw positive conclusions regarding the objective benefit of HM. Additional high quality studies are needed with more rigorous methodological approach to answer this question.

A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer.

PURPOSE: Pemetrexed and vinorelbine are active antineoplastic agents in non-small cell lung cancer (NSCLC). Phase I objectives include maximum tolerated dose (MTD) and recommended phase II dose determination, and pharmacokinetics of the pemetrexed-vinorelbine doublet in locally advanced or metastatic solid tumor patients (pts). Phase II objectives include tumor response evaluation, efficacy, and toxicity for first-line treatment of advanced NSCLC. EXPERIMENTAL DESIGN: Phase I pts received pemetrexed (day 1, 300-700 mg/m2) and vinorelbine (days 1 and 8, 15-30 mg/m2) every 21 days. Pharmacokinetics determined at cycle 1. Beginning with dose-level 3, folic acid and Vitamin B12 supplementation were given. RESULTS: Thirty-one phase I pts were enrolled. MTD was pemetrexed 700 mg/m2 and vinorelbine 30 mg/m2; and recommended phase II dose was pemetrexed 500 mg/m2 and vinorelbine 30 mg/m2. When administered in combination, pemetrexed and vinorelbine pharmacokinetics were consistent with single-agent administration. Thirty-seven (36 chemonaive) phase II NSCLC pts received pemetrexed-vinorelbine. Evaluable tumor response was 40%, with intent-to-treat 38%. One drug-related death occurred from febrile neutropenia with Staphylococcal infection. Grade 3/4 hematologic toxicities were neutropenia (65%) and febrile neutropenia (11%), while prevalent grade 3/4 non-hematologic toxicity was fatigue (27%). CONCLUSION: The pemetrexed-vinorelbine combination is well tolerated and shows activity as first-line treatment in advanced NSCLC patients.

The development of a model of outpatient chemotherapy delivery--chemotherapy basic treatment equivalent (CBTE).

The aims of this study were to study the patient-, tumour- and treatment-related factors that significantly impact on treatment episode duration for outpatient chemotherapy treatment delivery, and to develop a new measure of outpatient chemotherapy throughput that considers variations in treatment duration compared with the older measures of patients treated per day. A pilot study in our institution randomly measured the duration of outpatient chemotherapy delivery for 266 occasions of service. Patient, tumour and treatment factors were collected and assessed for their impact on treatment duration using multivariate analysis. A new model of outpatient chemotherapy was developed using various modeling processes. Median treatment duration was 90 min. Significant factors that impacted on treatment duration were the chemotherapy regimen, type of infusion, patient age and whether the patients required a community nurse to be organized. A measure was developed (Chemotherapy Basic Treatment Equivalent or CBTE) that considers the variations in treatment duration and showed that although the daily number of patients treated in our department each day remained stable, there were wide fluctuations in workload when variations in treatment duration were considered. A new measure of chemotherapy workload has therefore been proposed although further testing across departments is required. If broadly implemented this could substantially improve resource planning, resource use and patient satisfaction as it considers variations in treatment duration, which is not previously considered in chemotherapy throughput statistics.

A 27-year-old man with diplopia, fatiguable ptosis and rash: a rare presentation of angiocentric T cell lymphoma with lymphomatoid vasculitis.

A 27-year-old man presented with a 36-h history of ptosis and diplopia and a 10-day history of a lower limb rash. Skin biopsy revealed an aggressive angiocentric γδ-T cell lymphoma. The patient's symptoms and signs disappeared within 1 week of commencement of chemotherapy and there are plans for allogeneic stem cell transplantation.

Safety of trastuzumab (Herceptin) during pregnancy: two case reports.

We report on two cases of women on trastuzumab therapy for breast cancer who became pregnant and delivered healthy live infants. At the time of reporting the children are growing and developing normally (ages 3 and 2).

Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study.

BACKGROUND: Edrecolomab is a murine monoclonal antibody to the cell-surface glycoprotein 17-1A, which is expressed on epithelial tissues and on various carcinomas. Preliminary data suggested that it might be of use in the adjuvant treatment of patients with resected stage III colon cancer. We did a randomised trial in 27 countries to determine the effect of adding edrecolomab to the combination of fluorouracil and folinic acid in these patients. METHODS: After surgery, 2761 patients were randomly assigned edrecolomab plus fluorouracil-folinic acid (combination therapy [n=912]); fluorouracil-folinic acid alone (chemotherapy [n=927]); or edrecolomab alone (edrecolomab monotherapy [n=922]). Patients were assessed for survival and disease recurrence after surgery. The primary endpoint tested the hypothesis that combination therapy improved overall survival relative to chemotherapy. The key secondary endpoint was to test whether edrecolomab monotherapy was non-inferior to chemotherapy in terms of disease-free survival. Analysis was by intention to treat. FINDINGS: Median follow-up time was 26 months (IQR 20-36). 3-year overall survival on combination therapy was no different from that on chemotherapy (74.7% vs 76.1%, hazard ratio 0.94 [95% CI 0.76-1.15], p=0.53). Disease-free survival was significantly lower on edrecolomab monotherapy than on chemotherapy (53.0% vs 65.5%, 0.62 [0.53-0.73], p<0.0001). Hypersensitivity reactions occurred in 452 (25%) patients receiving edrecolomab, causing treatment discontinuation in 71 (4%). The addition of edrecolomab to chemotherapy did not increase neutropenia, diarrhoea, or mucositis. INTERPRETATION: The addition of edrecolomab to fluorouracil and folinic acid in the adjuvant treatment of resected stage III colon cancer does not improve overall or disease-free survival, and edrecolomab monotherapy is associated with significantly shorter overall and disease-free survival than fluorouracil and folinic acid and is therefore an inferior treatment option. Edrecolomab is well tolerated and its addition to fluorouracil and folinic acid does not increase the toxicity of chemotherapy.