Trabectedin as a chemotherapy option for patients with BRCA deficiency.

Trabectedin is a marine-derived product that was originally isolated from the Caribbean sea squirt Ecteinascidia turbinata and the first anticancer marine drug to be approved by the European Union. It is currently used as a single agent for the treatment of patients with soft tissue sarcoma after failure of anthracyclines and ifosfamide, or for those patients who are unsuited to receive these agents, and in patients with relapsed, platinum-sensitive ovarian cancer in combination with pegylated liposomal doxorubicin. Trabectedin has a unique multi-faceted mechanism of action that involves transcription regulation and DNA repair systems, including transcription-coupled nucleotide excision repair and homologous recombination repair (HRR) as the main hallmarks of its antiproliferative activity.

Nibrin is a marker of clinical outcome in patients with advanced serous ovarian cancer treated in the phase III OVA-301 trial.

Objective: This study investigated the relationship between 13 proteins involved in DNA damage and the outcomes of patients with recurrent ovarian cancer (ROC).

Patients And Methods: Immunohistochemistry staining was performed in 114 diagnostic samples from patients with serous ROC who participated in the OVA-301 study, which compared pegylated liposomal doxorubicin (PLD) with a combination of trabectedin plus PLD. Percentage of positive cells for every marker was calculated and correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Efficacy and safety of trabectedin as an early treatment for advanced or metastatic liposarcoma and leiomyosarcoma.

Aims: We aimed to evaluate the effect of prior chemotherapies on the outcomes of patients with liposarcoma and leiomyosarcoma treated with trabectedin as a 24-h infusion every 3 weeks.

Patients & Methods: Data from 129 patients who received trabectedin as second-line treatment following failure with an anthracycline/ifosfamide and those who had received at least two lines of prior chemotherapy were analyzed.

Results: Forty seven patients received one prior regimen (group A) and 82 patients received at least two lines of chemotherapy (group B).

Trabectedin as a new chemotherapy option in the treatment of relapsed platinum sensitive ovarian cancer.

Trabectedin (ET-743, Yondelis®) is a novel marine antineoplastic alkaloid with a unique mechanism of action. The active substance trabectedin, a tetrahydroisoquinoline alkaloid, is a natural product originally isolated from the Caribbean sea squirt, Ecteinascidia turbinata and is currently manufactured by total synthesis. Trabectedin is licensed by the Spanish pharmaceutical drug company, PharmaMar and co-developed by Johnson & Johnson Pharmaceutical Research and Development, L.

Trabectedin in pre-treated patients with advanced or metastatic soft tissue sarcoma: a phase II study evaluating co-treatment with dexamethasone.

Purpose: This study assesses the efficacy, toxicity and pharmacokinetic profile of trabectedin with or without prophylactic dexamethasone co-treatment in patients with recurrent advanced soft tissue sarcoma (STS).

Patients And Methods: Patients were randomized to receive trabectedin as a 3-h infusion every 3 weeks with dexamethasone or placebo in the first cycle, with the alternate in the second cycle and with the patient's choice subsequently. Due to toxicity, the randomized design was modified to open-label to make dexamethasone mandatory and the initial dose (1,650 μg/m(2)) was reduced to 1,500 μg/m(2) and then to 1,300 μg/m(2).

Phase II study of weekly Kahalalide F in patients with advanced malignant melanoma.

This phase II clinical trial evaluated the antitumour response of Kahalalide F (KF) 650 microg/m(2) given as a 1-h weekly infusion in advanced malignant melanoma patients, both untreated and those who relapsed or progressed after one line of systemic therapy. Of 24 enrolled patients (median age, 55 years; range, 28-89), 14 patients had been previously treated with chemotherapy or biological therapy. No RECIST responses occurred; five chemotherapy-naïve patients with cutaneous melanoma had disease stabilisation for > or = 3 months; median progression-free survival was 1.

Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.

Objective: To evaluate the antitumor activity and safety profile of plitidepsin administered as a 1h weekly intravenous (i.v.) infusion of 3.

Alterations in intestinal contractility during inflammation are caused by both smooth muscle damage and specific receptor-mediated mechanisms.

Aim: To evaluate motoric intestinal disturbances during inflammation with Trichinella spiralis in rats as an experimental model.

Methods: We examined the changes in worm-positive (jejunum) and worm-free (ileum) intestinal segments of rats infected with T. spiralis.

Gefitinib: current status in the treatment of non-small cell lung cancer.

Gefitinib (Iressa) is a novel drug approved in 28 countries (as of June 2004), including Japan, the US, Canada and Australia as second- and third-line monotherapy for the treatment of locally advanced or metastatic non-small cell lung cancer refractory to prior chemotherapy. Gefitinib is an orally active, epidermal growth factor receptor (EGFR)-tyrosine kinase (EGFR-TK) reversible inhibitor which blocks EGFR phosphorylation and subsequent signal transduction pathways involved in proliferation, metastasis, angiogenesis and apoptosis inhibition. Recently, mutations in the TK domain of the EGFR have been identified in those patients with refractory non-small cell lung cancer who achieved dramatic tumor responses to gefitinib.

Changes in the inhibitory responses to electrical field stimulation of intestinal smooth muscle from Trichinella spiralis infected rats.

Functional motor changes and morphological alterations have been associated with intestinal inflammation. The aim of this work was to study functional motor changes in inflamed and non-inflamed intestinal segments of Trichinella spiralis infected rats. Thickness of muscle layers and cell infiltration during infection were also evaluated.