Non-pegylated liposomal doxorubicin plus ifosfamide in metastatic soft tissue sarcoma: results from a phase-II trial

Non-pegylated liposomal doxorubicin (NPLD) has demonstrated antitumour activity equivalent to conventional doxorubicin and a significantly lower risk of cardiotoxicity. This phase II trial was performed to evaluate the activity and the safety of NPLD and ifosfamide combination in patients with metastatic soft tissue sarcoma

Lack of Activity of Docetaxel in Soft Tissue Sarcomas: Results of a Phase II Study of the Italian Group on Rare Tumors

Purpose. The prognosis of advanced soft tissue sarcoma is poor, only a few drugs showing some activity with response rates around 15– 25%. Consequently drug development seems mandatory to improve treatment outcome. Following previous favourable EORTC experience, the Italian Group on Rare Tumors started a phase II study with docetaxel to confirm the activity of this drug in soft tissue sarcoma

An exploratory study to identify risk factors for the development of capecitabine-induced palmar plantar erythrodysesthesia (PPE)

Aims: to identify pre-treatment risk factors for the development of Palmar Plantar Erythrodysesthesia in participants receiving capecitabine monotherapy. Specifically the hypothesis that avoidance of activities that cause friction and pressure cause Palmar Plantar Erythrodysesthesia was tested. Background. Previous literature showed contradictory evidence on the subject of predictors of chemotherapy-induced Palmar Plantar Erythrodysesthesia. There is a lack of empirical evidence to support the theory that Palmar Plantar Erythrodysesthesia is caused by damage to the microcapillaries due to everyday activities that cause friction or pressure to the hands or feet. Design. Prospective epidemiological study of risk factors. Methods. Prospective data collection. All patients prior to commencing capecitabine monotherapy between 11 June 2009–31 December 2010, were offered recruitment into the study and followed up for six cycles of treatment (n = 174). Data were collected during semi-structured interviews, from participants’ diaries, physical examination of the hands and feet and review of notes. Data relating to activities that cause friction, pressure or heat were collected. Data were analysed using bivariate (chi-square and independent groups Student’s t) tests where each independent variable was analysed against Palmar Plantar Erythrodysesthesia. Results. The only variables that were associated with an increased risk of Palmar Plantar Erythrodysesthesia were a tendency to have warm hands and pre-existing inflammatory disease. Conclusions. This study gives no support for the hypothesis that avoidance of activities that cause friction and pressure cause Palmar Plantar Erythrodysesthesia

Dovitinib in patients with gastrointestinal stromal tumour refractory and/or intolerant to imatinib

This multicentre phase II trial (DOVIGIST) evaluated the antitumour activity of dovitinib as second-line treatment of patients with gastrointestinal stromal tumour (GIST) refractory to imatinib or who do not tolerate imatinib. Patients received oral dovitinib 500mgday1, 5 days on/2 days off, until GIST progression or unacceptable toxicity, with an objective to evaluate efficacy, assessed as the disease control rate (DCR) at 12 weeks. Tumour assessment and response to dovitinib therapy were evaluated by Response Evaluation Criteria In Solid Tumours (RECIST v1.1) and the Choi criteria. Secondary objectives included assessment of progression-free survival (PFS), safety and tolerability, and DCR at the end of treatment. Thirty-eight of the 39 patients enrolled had histologically confirmed GIST. The DCR at 12 weeks was 52.6% (90% confidence interval (CI), 38.2-66.7%) meeting the preset efficacy criterion for the primary end point. The objective response rate (complete responsepartial response) was 2.6% (1 of 38; 90% CI, 0.1-11.9%), and 5.3% (n=2; 90% CI, 0.9-15.7%) at the end of the study. The median PFS was 4.6 months (90% CI, 2.8-7.4 months). Dose interruption was required in 26 patients (66.7%), of which 18 (69.2%) were due to adverse events. The most frequently observed grade 3 adverse events included hypertension (n=7), fatigue (n=5), vomiting (n=4), hypertriglyceridaemia (n=4), and g-glutamyltransferase increase (n=4). Dovitinib is an active treatment for patients with GIST who are intolerant to imatinib or whose GIST progresses on imatinib

Trabectedin for patients with advanced soft tissue sarcoma: A non-interventional, retrospective, multicenter study of the italian sarcoma group

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050)