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| |  Figitumumab Has Antitumour Activity in Ewing’s Sarcoma NEW YORK -- December 23, 2009 -- A preliminary study of figitumumab has found that it has antitumour activity in Ewing’s sarcoma. The results have led to the drug’s progression to a phase 2 trial in patients with Ewing’s sarcoma, which has recently finished recruiting. The study, led by Johann S de Bono, MD, The Institute for Cancer Research (ICR), and The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, is published online first and will appear in an upcoming issue of The Lancet Oncology. Data from preclinical studies have suggested that Ewing’s sarcoma, and some other sarcoma subtypes, are dependent on the insulin-like growth factor signalling pathway. Figitumumab is a drug which targets the insulin-like growth-factor-1 receptor (IGF-1R). This phase I study was carried out to assess the effects of figitumumab in these sarcoma subtypes. Between January, 2006 and August, 2008, patients with refractory, advanced sarcomas received figitumumab 20 mg/kg in 2 groups within a phase 1 trial. The first cohort (15 patients) included patients with multiple sarcoma subtypes, age 18 years or older, and the second cohort (14 patients) consisted of patients with refractory Ewing’s sarcoma, aged 9 years or older. The primary endpoint was to assess the safety and tolerability of figitumumab. Of the 29 patients that were enrolled, 16 had Ewing’s sarcoma, and the 29 received a total of 177 cycles of treatment (median 2, mean 6, range 1 to 24). In terms of adverse events, grade 3 deep venous thrombosis, grade 3 back pain, and grade 3 vomiting were each noted once in individual patients; 1 patient had grade 3 or 4 raised liver enzymes. The only other grade 4 adverse event was raised concentrations of uric acid, noted in 1 patient. A total of 28 patients were assessed for response; 2 patients, both with Ewing’s sarcoma, had objective responses (1 complete response and 1 partial response) and 8 patients had disease stabilisation (6 with Ewing’s sarcoma, 1 with synovial sarcoma, and 1 with fibrosarcoma) lasting 4 months or longer. “Figitumumab is well tolerated and has antitumour activity in Ewing’s sarcoma, warranting further investigation in this disease,” the authors wrote. “Our results show that figitumumab can be safe for both adult and paediatric sarcoma patients, and has single-agent antitumour activity in different sarcoma subtypes, including Ewing’s sarcoma. Phase 2 studies of figitumumab and other anti-IGF-R agents in Ewing’s sarcoma and other sarcoma subtypes are now completing accrual and rational combinations with other treatments are also being pursued.” In an accompanying comment, Jeffrey A Toretsky, MD, Georgetown University, Washington DC, and Richard Gorlick, MD, Albert Einstein College of Medicine of Yeshiva University, The Children’s Hospital at Montefiore, Bronx, New York, said: “With several different companies developing IGF-1R inhibitors, there could be ample opportunity to optimise clinical benefit from IGF-1R blockade, although the development of these antibodies may be complicated. Five-drug chemotherapy is routine in the treatment of Ewing’s sarcoma, therefore improvement in outcome for these patients will likely require demonstration of the feasibility of combining the antibody with standard chemotherapy. Ultimately, a phase 3 randomised study investigating the benefit of this combination might provide the proof of activity that will achieve the IGF-1R-pathway promise.”
SOURCE: The Lancet Oncology
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