Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
J Clin Oncol ; 29(34): 4534-40, 2011 Dec 01.
Article in English | MEDLINE | ID: mdl-22025154

ABSTRACT

PURPOSE: Patients with Ewing sarcoma (ES) with metastases and those who relapse fare poorly and receive therapies that carry significant toxicity. This phase 1/2 study was conducted to evaluate the efficacy of figitumumab in advanced ES. PATIENTS AND METHODS: Patients with sarcoma 10 to 18 years old were enrolled in two dose escalation cohorts (20 and 30 mg/Kg intravenously every 4 weeks) in the phase 1 portion of the study. Patients with ES 10 years old or older were enrolled in the phase 2 portion of the study. The primary phase 2 objective was objective response rate (ORR). RESULTS: Thirty-one patients with ES (n = 16), osteosarcoma (n = 11), or other sarcomas (n = 4) were enrolled in the phase 1 portion of the study. Dose escalation proceeded to 30 mg/kg every 4 weeks with no dose-limiting toxicity identified. In the phase 2 portion of the study, 107 patients with ES received figitumumab at 30 mg/kg every 4 weeks for a median of 2 cycles (range, 1 to 16). Sixty three percent of phase 2 patients had received at least three prior treatment regimens. Of 106 evaluable patients, 15 had a partial response (ORR, 14.2%) and 25 had stable disease. Median overall survival was 8.9 months. Importantly, patients with a pretreatment circulating free insulin-like growth factor (IGF) -1 lower than 0.65 ng/mL (n = 14) had a median OS of 3.6 months, whereas those with a baseline free IGF-1 ≥ 0.65 ng/mL (n = 84) had a median OS of 10.4 months (P < .001). CONCLUSION: Figitumumab had modest activity as single agent in advanced ES. A strong association between pretreatment serum IGF-1 and survival benefit was identified.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Bone Neoplasms/drug therapy , Receptor, IGF Type 1/immunology , Sarcoma, Ewing/drug therapy , Adolescent , Adult , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents/adverse effects , Female , Humans , Immunoglobulins, Intravenous , Male , Middle Aged , Receptor, IGF Type 1/blood , Recurrence , Retreatment
2.
Rev Recent Clin Trials ; 5(3): 189-208, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20533896

ABSTRACT

Progress has been made towards the development of agents targeting tyrosine kinase receptors and other molecules involved in signalling pathways important for cell proliferation, motility, and apoptosis. Inhibitor molecules designed to be highly specific with the aim of decreasing toxicity have proven to be generally well tolerated. However, the efficacy of targeted agents may be impacted by cross-talk between pathways and downregulation of negative feed-back loops. That is the case of the IGF-IR/PI3K/Akt/mTOR pathway. This issue raises the question of how these targeted agents could be combined to prevent or delay resistance without significantly increasing toxicity. Several mTOR inhibitors have been approved for cancer therapy, and late-stage clinical trials of IGF-IR inhibitors are underway. The outcome of ongoing clinical studies of IGF-IR, PI3K, Akt and mTOR inhibitors as well as further testing of the combination of these agents will be key for the development of therapeutic options in a wide range of oncology indications.


Subject(s)
Antineoplastic Agents/therapeutic use , Intracellular Signaling Peptides and Proteins/antagonists & inhibitors , Neoplasms , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Receptor, IGF Type 1/antagonists & inhibitors , Signal Transduction/drug effects , Trans-Activators/antagonists & inhibitors , Apoptosis/drug effects , Clinical Trials as Topic , Drug Screening Assays, Antitumor , Humans , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology , Phosphoinositide-3 Kinase Inhibitors , TOR Serine-Threonine Kinases
SELECTION OF CITATIONS
SEARCH DETAIL
...