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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hormone-refractory prostate cancer (HRPC) is associated with a poor prognosis and has historically been considered relatively chemoresistant. Emerging data demonstrate clinical benefit with the use of docetaxel in HRPC, culminating in two recent published phase III studies demonstrating survival benefit. Currently, docetaxel is registered but not reimbursed for HRPC in Australia. Aim: To retrospectively review prostate-specific antigen (PSA) response rate, and survival following the use of docetaxel for metastatic HRPC. Methods: Retrospective audit of the use of docetaxel for HRPC from 1 January 2001 to 1 April 2004 in three medical oncology practices. Demographic data, baseline PSA, ECOG (Eastern Cooperative Oncology Group) Performance Status, sites of disease, number of cycles received and PSA response rates were collected. Results: Thirty five patients (median age, 71 years; range, 50–88) had an ECOG status of 0 (eight), 1 (20) and 2 (seven). The mean duration from initial prostate cancer diagnosis to start of docetaxel was 5.4 years (range, 0.2–13.5 years). The mean baseline PSA doubling time, available for 29/35 patients, was 1.9 months (range, 0.4–4.9). The median number of metastatic sites was 1 (range, 1–4): bone (34 patients), lymph nodes (10), liver (seven) and lung (seven). Twelve patients were chemotherapy naive; 23 had received prior chemotherapy (21/23 received mitoxantrone). Twenty patients received docetaxel three times weekly; 15 were on weekly schedules. Their mean dose density was 23 mg/m2/week. Patients received an average of 3.2 months of treatment (range, 0.2–11.8). There were 170 recorded toxicities, 13 of which were grade 3–4, and two likely treatment-related deaths (sepsis). Twelve patients (34%) had >50% PSA response (four were chemotherapy naive); of these 12 responders, seven patients had a >75% PSA response (four chemotherapy naive). Median survival from start of docetaxel was 8 months with 37% alive at 12 months and 23% alive at 24 months. Conclusion: Docetaxel is active in HRPC (in both chemotherapy naive and exposed patients) with a predictable toxicity profile. More research is warranted to identify predictors of response and toxicity. [ABSTRACT FROM AUTHOR]