A Phase I/II Clinical Trial of Belinostat (PXD101) in Combination with Doxorubicin in Patients with Soft Tissue Sarcomas

Background. Belinostat is a novel histone deacetylase inhibitor. Primary Objectives. Maximum tolerated dose (MTD) and dose limiting toxicities (DLTs) of belinostat (Bel) in combination with doxorubicin (Dox) in solid tumours (phase I) and response rate (RR) in soft tissue sarcomas (phase II). Methods. Bel was administered as a 30-minute IV infusion on days 1–5 and on day 5 with Dox. The dose escalation schedule was as follows: cohort 1: Bel 600 mg/m2 and 50 mg/m2 Dox, cohort 2: Bel 600 mg/m2 and 75 mg/m2 Dox, cohort 3: Bel 800 mg/m2 and 75 mg/m2 Dox, and cohort 4: Bel 1000 mg/m2 and 75 mg/m2 Dox. Results. 41 patients were included (25 in phase I, 16 in phase II). Adverse events were fatigue (95%), nausea (76%), and alopecia (63%). There was one DLT, grade 3 rash/hand and foot syndrome. MTD was Bel 1000 mg/m2/d and Dox 75 mg/m2. Four responses were seen: 2 PR in phase I, RR of 8%; in phase II, 1 PR/1 CR, RR of 13%, and 9 patients (56%) with SD. Conclusion. The combination was well tolerated. Response rate was moderate but median time to progression was 6.0 months (95% CI, 1.6–9.7 months) which is superior to some reports of single-agent Dox

Metastatic Pattern, Local Relapse, and Survival of Patients with Myxoid Liposarcoma:A Retrospective Study of 45 Patients

Purpose. To assess the metastatic pattern of the histological subtype myxoid liposarcoma (MLS) with no or few round cells. Methods. Forty-five patients (F/M = 27/18, mean age 49 (range 17–85) years) were diagnosed with MLS at two Danish sarcoma centres in the period 1995–2004. A retrospective review of patients' files combined with an extraction of survival data from the Danish Centralised Civil Register was performed. Results. Seven patients had distant metastases during the observation period. Two patients had metastases at the time of diagnosis, while metastases occurred within 2.5 years in four patients, and in one patient 11.9 years after primary diagnosis. All metastases occurred at extrapulmonary sites. The first local relapse occurred within 3 years after surgery in six patients, in one patient after 4.0 years, and in one patient 7.7 years after surgery. The 5- and 10-year overall survival was 80% and 69%, respectively. Both the 5- and 10-year distant metastases-free survival was, respectively, 86%. The 5- and 10-year local relapse-free survival was, respectively, 83% and 80%. Conclusions. Patients with MLS had only extra-pulmonary metastases, and no lung metastases were found. Most local relapses and distant metastases occurred within the first 2-3 years after surgery

Epithelioid hemangioendothelioma, an ultra-rare cancer : a consensus paper from the community of experts

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication