A prospective multi-centre, randomized study comparing the addition of tapering dexamethasone to other standard of care therapies for taxane-associated pain syndrome (TAPS) in breast cancer patients.

PURPOSE: Taxane-associated pain syndrome (TAPS) is common with docetaxel and is characterised by myalgias and arthralgias starting 2-3 days after treatment and can last for up to 7 days. Anecdotal evidence suggests that corticosteroids can reduce TAPS. This multicentre, randomized trial evaluated the effect of additional tapering dexamethasone on TAPS. METHODS: 130 breast cancer patients commencing docetaxel were randomized to dexamethasone premedication (8 mg/twice daily for 3 days) or dexamethasone premedication followed by tapering dexamethasone (4 mg/daily for 2 days followed by 2 mg/daily for 2 days). The primary endpoint was absolute change in FACT-Taxane questionnaire during the first chemotherapy cycle. Secondary endpoints: proportion of patients with clinically significant TAPS, QoL, pain and toxicity. RESULTS: 110/130 patients had complete data included in the primary analysis. The fall in FACT-Taxane scores was lower in the experimental group on day 5 (p = 0.05), but not on day 7 (p = 0.21). There was no difference in FACT-Taxane scores over the entire study duration (p = 0.59). Fewer patients in the experimental arm reported TAPS on day 5 (30 vs. 47%). There was a borderline significant attenuation of impairment of QoL with experimental treatment on day 5 (p = 0.06), but not day 7 (p = 0.53). Tapered schedule was associated with more dyspepsia and insomnia. CONCLUSION: A tapering schedule of dexamethasone was associated with a brief reduction in docetaxel-associated symptoms which was observed only during dexamethasone exposure and did not persist after discontinuation of the drug. TRIAL REGISTRATION: ClinicalTrials.gov NCT03348696.

Phase II multicenter trial of anthracycline rechallenge with pegylated liposomal doxorubicin plus cyclophosphamide for first-line therapy of metastatic breast cancer previously treated with adjuvant anthracyclines.

PURPOSE: Anthracyclines are a component of breast cancer chemotherapy regimens in both adjuvant and metastatic settings. Anthracycline rechallenge for metastatic disease, for those previously exposed to adjuvant anthracyclines, may not be considered because of concerns about efficacy, tolerability, and cumulative cardiotoxicity. PATIENTS AND METHODS: This prospective, multicenter, single-arm, phase II trial examined the efficacy and safety of pegylated liposomal doxorubicin (PLD) 35 mg/m(2) plus cyclophosphamide 600 mg/m(2) as first-line therapy, delivered every 3 weeks, in 70 patients who developed metastatic disease more than 12 months after completion of an adjuvant anthracycline-containing regimen. Seven patients discontinued treatment early and were excluded from the efficacy analysis. RESULTS: After a median of six cycles, the objective response rate was 38%. An additional 33% of patients achieved stable disease lasting more than 6 months, for an overall clinical benefit rate of 71%. The estimated median time to progression was 12.2 months. Median overall survival time was 16.5 months. Clinical response was equally robust in patients with and without prior taxane exposure. Treatment was well tolerated. The most common grade 3 to 4 toxicities were palmar-plantar erythrodysesthesia (PPE; 10%), dyspnea (9%), and neutropenia (9%). One (1.4%) of 70 patients discontinued treatment as a result of PPE. One patient (1.4%) experienced an infusion reaction requiring discontinuation. No symptomatic cardiac events were observed. CONCLUSION: PLD plus cyclophosphamide is effective and well tolerated in patients with metastatic breast cancer who have received prior adjuvant anthracycline-containing chemotherapy. The majority of patients experienced a clinical benefit without any significant impact on cardiac function.