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Background and purpose: Paclitaxel is a widely used anti-neoplastic agent but has low oral bioavailability due to gut extrusion by P-glycoprotein (P-gp). Oral paclitaxel could be more convenient, less resource intensive, and more tolerable than intravenous administration. Encequidar (HM30181A) is a novel, minimally absorbed gut specific P-gp inhibitor. We tested whether administration of oral paclitaxel with encequidar (oPac+E) achieved comparable AUC to intravenous paclitaxel (IVP) 80mg/m2. Experimental approach: We conducted a multi-centre randomised crossover study with two treatment periods. Patients (pts) with advanced cancer received either oral paclitaxel 615mg/m2 divided over three days and encequidar 15mg orally one-hour prior, followed by IVP 80mg/m2, or the reverse sequence. PK blood samples were taken up to day 9 for oPac+E and day 5 for IVP. Key Results: 42 pts were enrolled; 35 completed both treatment periods. AUC0-∞was 5033.5 +/- 1401.1 ng.h/mL for oPac+E and 5595.9 +/- 1264.1 ng.h/mL with IVP. The geometric mean ratio (GMR) for AUC was 89.5% (90% CI 83.9-95.5). Mean absolute bioavailability of oPac+E was 12%. PK parameters did not change meaningfully after 4 weeks administration of oPac+E in an extension study. G3 treatment emergent adverse events occurred in 7 (18%) pts with oPac+E and 2 (5%) with IVP. 75% of pts preferred oPac+E over IVP. Conclusion and Implications: GMR for AUC was within the predefined acceptable range of 80%-125% for demonstrating equivalence. oPac+E is tolerable and there is no evidence of P-gp induction with repeat administration. With further study, oPac+E is a candidate to replace IVP.

Objective Cardiovascular disease is the leading cause of death in breast cancer survivors. While evidence shows circuit resistance training (CRT) is effective for improving muscle and cardiorespiratory fitness, whether CRT is an efficacious therapy for decreasing cardiovascular risk in cancer survivors is unclear. Methods Fifty-one breast cancer survivors were recruited to either 12 weeks CRT (n = 26), or a non-exercising wait-list control (n = 25). Two supervised 60 min CRT sessions per week were undertaken, comprising resistance and functional exercises, and aerobic exercise stations. Primary outcome measure was the gold-standard assessment of arterial stiffness, aortic pulse wave velocity (PWV). Secondary outcomes included: cardiorespiratory fitness (CRF), upper and lower body strength, arterial wave reflections, central blood pressure and rate pressure product. Results Compared to the control group, the CRT group had a statistically significant medium effect decrease in PWV 0.9 m/s (95% CI: 0.1, 1.7). There were large effect improvements in VO2 max (4.3 ml kg-1 min-1 , 95% CI: 5.8, 2.8), upper and lower body strength (3.7 kg, 95% CI: 1.9, 5.6 and 10.4 kg, 1.6, 19.1) respectively. Conclusion Findings support the existing literature demonstrating that 12 weeks CRT improves muscle and cardiorespiratory fitness and is also an effective strategy for decreasing a proven cardiovascular risk factor in breast cancer survivors.

Background Breast cancer patients experience various side effects during cancer therapy, often resulting in reduced quality of life and poor adherence to treatment. A limited range of proven interventions has been developed to target such side effects. While Tai Chi offers benefits for the health and well-being of breast cancer survivors, the effectiveness of Tai Chi across the treatment continuum has not been evaluated. Improved patient education and support has been suggested as a priority for breast cancer care. This pilot study assesses the feasibility of a randomized controlled trial (RCT) to evaluate the effectiveness of “an integrative Tai Chi” (ANITA) program for breast cancer patients undergoing cancer therapy. Methods/design This is a single-centre, two-arm feasibility RCT. Twenty-four patients with breast cancer who have undergone surgical treatment will be recruited from the Dunedin Hospital (New Zealand) over a 12-month period (from August 2017 to July 2018). Subject to informed consent, patients will be randomized to receive standard cancer treatment alone or standard cancer treatment plus the ANITA program, consisting of peer support, health education, and Tai Chi Ruler exercise. The program runs alongside the patient’s adjuvant cancer therapy, which may include chemotherapy, radiation therapy, antibody treatment, and/or antihormonal therapy. Analysis in this study will focus on process evaluation of participant recruitment, retention, treatment fidelity, acceptability of the program, and occurrence of adverse events. Clinical outcomes (i.e., fatigue, sleep quality, anxiety and depression and quality of life) will be assessed at baseline, and at 12 weeks and 24 weeks post-randomization. Discussion Outcomes from this study will inform the feasibility and methodology for a future fully-powered RCT. Trial registration Australian New Zealand Clinical Trials Registry with the identifier ACTRN12617000975392.

With better detection and treatment, breast cancer is less likely to be the primary cause of death in the majority of breast cancer survivors; mortality due to cardiovascular disease (CVD) is now more common. Given the long latency periods between cancer treatment completion and potential symptomatic CVD, there is a need to detect vascular changes before symptoms appear. This short review provides an overview of non-invasive, widely available, and relatively inexpensive techniques for assessing endothelial function, central and regional arterial stiffness, central blood pressures, and intima-media thickness. These tools exhibit acceptable reliability and validity, and are relatively practical. Clinical assessment recommendations are also provided. There is sufficient evidence to encourage the use of these techniques as a component of routine serial assessments, and to help guide appropriate treatment strategies.

Background: Capecitabine and cyclophosphamide are active in patients with advanced breast cancer, have nonoverlapping toxic effects and synergy pre-clinically. We explored the efficacy and toxic effect of an all-oral combination of capecitabine with cyclophosphamide versus capecitabine alone in a multicentre, randomized, phase II study. Patients and methods: Patients with locally advanced or metastatic breast cancer were randomized to treatment with capecitabine given continuously (666 mg/m 2 b.i.d. days 1–28) alone (C) or with oral cyclophosphamide (100 mg/m 2 days 1–14 of a 28-day cycle) (CCy) for up to six cycles. Results: Eighty-two patients were randomized. There was no complete response. The proportions with partial response were 36% on C and 44% on CCy, a difference of 7.9% [95% confidence interval (CI) −13.4 to 29.1]. Significant toxic effect was uncommon: grade ≥3 diarrhoea in 4 (10%) versus 1 (3%) patients; grade ≥3 fatigue in 2 (5%) versus 5 patients (13%) and grade ≥2 hand-foot syndrome in 7 (17%) versus 11 (28%) patients receiving C versus CCy, respectively. Median progression-free survival was 3.1 months on C and 6.9 months on CCy, not significantly different statistically. There was no difference in overall survival. Conclusion: The difference in tumour response suggests a reasonable chance that CCy is superior to C alone.

Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

There is limited published literature on the risk of breast cancer in transgender patients. We report a case of an aggressive triple negative inflammatory breast cancer in a male-to-female transsexual. This patient had a complicated psychiatric history with significant antipsychotic use, and the case raises several questions about the pathogenesis of this breast cancer. The literature on breast cancer in transgender patients and in relation to hyperprolactinaemia is reviewed.

Dermatomyositis has a known association with malignancy. We report a case of dermatomyositis occurring in early-stage testicular cancer where the patient was in remission. It stresses the importance of considering testicular cancer as an association with dermatomyositis, as it is a potentially curable malignancy.