METHODS: We recruited 10 patients with advanced breast cancer with ECOG (Eastern Cooperative Oncology Group) performance status score of zero to two, who needed chemotherapy in the first or second-line setting to receive two-weekly docetaxel for 8 cycles. The primary endpoint was safety and secondary endpoints were response rate and progression free survival.
RESULTS: The most reported adverse events were haematological (anaemia 100% and neutropenia 90%). The febrile neutropenia rate was 10%. The overall response rate was 20%. The median progression free survival was 5.0 months.
CONCLUSION: Two-weekly docetaxel may be a reasonable alternative treatment regimen for patients with advanced breast cancer in the first or second-line setting. This regimen is yet to be compared with standard 3-weekly schedule in a phase 3 randomised clinical trial.
CASE REPORT: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up.
DISCUSSION: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.
METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147.
FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients.
INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma.
FUNDING: Novartis Pharmaceuticals, Janssen Pharmaceuticals, and Singhealth Foundation.