Abstract | PURPOSE: EXPERIMENTAL DESIGN: Patients with advanced solid tumors were assigned to receive i.v. R1507 weekly (qW), starting with 1 mg/kg. Subsequent cohorts were dosed at 3 and then 9 mg/kg. An additional 12 patients received 9 mg/kg R1507 qW. Patients remained on the study until the development of a dose-limiting toxicity or progressive disease. RESULTS: In total, 37 patients were treated with R1507 qW. No dose-limiting toxicities were identified and the maximum tolerated dose was not reached. The pharmacokinetics of R1507 were characterized by a slow clearance and limited volume of distribution, with an estimated elimination half-life justifying weekly administration. Serum IGF-I ligand levels increased proportionally to dose during the first 72 hours in all cohorts. R1507 was well tolerated. Two patients diagnosed with Ewing's sarcoma had partial responses of 11.5 and >26 months (ongoing at time of submission); 13 patients had stable disease; and 16 had progressive disease as best response by the Response Evaluation Criteria in Solid Tumors. CONCLUSION:
R1507 is well tolerated and shows antitumor activity in patients with solid neoplasms, in particular Ewing's sarcoma. The recommended dose for the weekly schedule is 9 mg/kg qW.
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Authors | Razelle Kurzrock, Amita Patnaik, Joseph Aisner, Terri Warren, Stephen Leong, Robert Benjamin, S Gail Eckhardt, Joseph E Eid, Gerard Greig, Kai Habben, Cinara D McCarthy, Lia Gore |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 16
Issue 8
Pg. 2458-65
(Apr 15 2010)
ISSN: 1557-3265 [Electronic] United States |
PMID | 20371689
(Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Receptor, IGF Type 1
- teprotumumab
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Topics |
- Administration, Oral
- Adolescent
- Adult
- Aged
- Antibodies, Monoclonal
(administration & dosage, pharmacokinetics)
- Antibodies, Monoclonal, Humanized
- Female
- Humans
- Male
- Maximum Tolerated Dose
- Middle Aged
- Neoplasms
(drug therapy, pathology)
- Receptor, IGF Type 1
(antagonists & inhibitors)
- Survival Rate
- Tissue Distribution
- Treatment Outcome
- Young Adult
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