Eltrombopag with gemcitabine-based chemotherapy in patients with advanced solid tumors: a randomized phase I study.

Preventing chemotherapy-induced thrombocytopenia could avoid chemotherapy dose reductions and delays. The safety and maximum tolerated dose of eltrombopag, an oral thrombopoietin receptor agonist, with gemcitabine-based therapy was evaluated. Patients with advanced solid tumors and platelets ≤300 × 10(9) /L receiving gemcitabine plus cisplatin or carboplatin (Group A) or gemcitabine monotherapy (Group B) were randomized 3:1 to receive eltrombopag or placebo at a starting dose of 100 mg daily administered on days -5 to -1 and days 2-6 starting from cycle 2 of treatment.

Results of a phase I dose escalation study of eltrombopag in patients with advanced soft tissue sarcoma receiving doxorubicin and ifosfamide.

Background: The objective of this Phase I dose escalation study was to explore the safety and tolerability of eltrombopag, an oral, nonpeptide, thrombopoietin receptor agonist, in patients with advanced soft tissue sarcoma (STS) and thrombocytopenia due to treatment with doxorubicin and ifosfamide (AI) combination chemotherapy.

Methods: Patients aged 18 or older with histologically confirmed, locally advanced or metastatic STS were treated with 1 cycle of AI followed by AI with eltrombopag starting at Cycle 2, using 2 different dosing schedules. The study design included an eltrombopag dose escalation phase starting at 75 mg daily to determine the optimal biological dose (OBD).

Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors.

Background: Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R) agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues.

Thrombopoietin receptor levels in tumor cell lines and primary tumors.

Thrombopoietin (TPO) receptor agonists represent a new approach for the treatment of thrombocytopenia, which may develop as a consequence of immune thrombocytopenia, chemotherapy treatment, chronic hepatitis C infection, or myelodysplastic syndromes. There are concerns that use of certain growth factors can hasten disease progression in some types of hematologic malignancies and solid tumors. In this study, expression of MPL (TPO-R) mRNA was examined in tumor cell lines, patient tumor samples (renal cell carcinoma, prostatic carcinoma, soft tissue and bony/cartilage sarcoma, colon cancer, and lymphoma), and normal tissues using microarray analysis and qRT-PCR.

A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors.

Objectives: Eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist, has been shown to increase platelet counts in adults with chronic immune thrombocytopenia and chronic hepatitis C. This multicenter phase 2 study assessed the efficacy and safety of eltrombopag in patients receiving first-line carboplatin/paclitaxel for the treatment of advanced solid tumors.

Research Design And Methods: Patients (N = 183) were randomized to placebo or eltrombopag 50 mg, 75 mg, or 100 mg given orally following chemotherapy on days 2 through 11 of each 21-day cycle, for at least two cycles.