Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer
| Autor: | Rira Watanabe, Archie N. Tse, David C. McKee, Mendel Jansen, Sze Ting Lee, Graeme O'Keefe, Martin W. Brechbiel, Fook-Thean Lee, Niall C. Tebbutt, Geoffrey Chong, Andrew M. Scott, Marika Ciprotti, Wendie Hopkins, Manabu Matsumura, Jonathan Greenberg, Fiona Scott, Masakatsu Kotsuma, Sylvia J. Gong, Ralph Venhaus, Bridget Chappell, Robert A. Beckman, Hui K Gan |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Biodistribution Colorectal cancer medicine.medical_treatment Pharmacology Antibodies Monoclonal Humanized Cohort Studies chemistry.chemical_compound Pharmacokinetics Internal medicine Pancreatic cancer medicine Humans Tissue Distribution Neoplasm Metastasis Tigatuzumab Radionuclide Imaging Aged Aged 80 and over Chemotherapy Dose-Response Relationship Drug business.industry Indium Radioisotopes Middle Aged medicine.disease chemistry Pharmacodynamics Monoclonal Female Radiopharmaceuticals Colorectal Neoplasms business |
| Zdroj: | Journal of Clinical Oncology. 33:2609-2616 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2014.60.4256 |
| Popis: | Purpose CS-1008 (tigatuzumab) is a humanized, monoclonal immunoglobulin G1 (IgG1) agonistic antibody to human death receptor 5. The purpose of this study was to investigate the impact of CS-1008 dose on the biodistribution, quantitative tumor uptake, and antitumor response in patients with metastatic colorectal cancer (mCRC). Patients and Methods Patients with mCRC who had received at least one course of chemotherapy were assigned to one of five dosage cohorts and infused with a weekly dose of CS-1008. Day 1 and day 36 doses were trace-labeled with indium-111 (111In), followed by whole-body planar and regional single-photon emission computed tomography (SPECT) imaging at several time points over the course of 10 days. Results Nineteen patients were enrolled. 111In-CS-1008 uptake in tumor was observed in only 12 patients (63%). 111In-CS-1008 uptake and pharmacokinetics were not affected by dose or repeated drug administration. 111In-CS-1008 biodistribution showed gradual blood-pool clearance and no abnormal uptake in normal tissue. No anti–CS-1008 antibody development was detected. One patient achieved partial response (3.7 months duration), eight patients had stable disease, and 10 patients had progressive disease. Clinical benefit rate (stable disease + partial response) in patients with 111In-CS-1008 uptake in tumor was 58% versus 28% in patients with no uptake. An analysis of individual lesions showed that lesions with antibody uptake were one third as likely to progress as those without antibody uptake (P = .07). Death-receptor–5 expression in archived tumor samples did not correlate with 111In-CS-1008 uptake (P = .5) or tumor response (P = .6). Conclusion Death-receptor–5 imaging with 111In-CS-1008 reveals interpatient and intrapatient heterogeneity of uptake in tumor, is not dose dependent, and is predictive of clinical benefit in the treatment of patients who have mCRC. |
| Databáze: | OpenAIRE |
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