| Phase I study of TLR9 agonist PF-3512676 in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer. | |
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MedLine Citation:
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PMID: 19843072 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This phase I, open-label study investigated the Toll-like receptor 9 agonist, PF-3512676, in combination with carboplatin and paclitaxel in Japanese patients with advanced, non-small-cell lung cancer (NSCLC). Patients (n = 12) with treatment-naive stage IIIB or IV NSCLC received single-agent PF-3512676 subcutaneously once during the first 7 days (monotherapy phase) in three escalating dose levels (0.1, 0.2, and 0.4 mg/kg) followed by a combination phase during which patients received 0.1 or 0.2 mg/kg PF-3512676 subcutaneously on days 8 and 15 of each 3-week cycle of carboplatin (area under the curve, 6 mg x min/mL) and paclitaxel (200 mg/m(2)). Safety and pharmacokinetics of PF-3512676 were assessed during monotherapy and combination therapy phases. PF-3512676 was tolerable as monotherapy or in combination with chemotherapy in patients with NSCLC. Most common treatment-related, non-hematologic adverse events (AEs) throughout the study were injection-site reactions (n = 12, 100%) and flu-like symptoms (n = 11, 91.7%) that were each grade 1 or 2 in all but one patient. All patients experienced neutropenia and leukopenia (>or=grade 3 in 11 [91.7%] and seven [58.3%] patients, respectively). One patient in dose level 2 had a dose-limiting toxicity: grade 3 rash and grade 3 increase in gamma-glutamyltransferase during combination therapy. Mean PF-3512676 half-life ranged from 4.8 to 21.6 h (longer with higher doses). Four (33%) patients had objective responses (one complete response, three partial responses), and seven (58%) patients achieved stable disease. PF-3512676 as monotherapy and in combination with chemotherapy had an acceptable safety profile in Japanese patients with treatment-naive NSCLC. |
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Authors:
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Kazuhiko Yamada; Masao Nakao; Chikara Fukuyama; Hiroshi Nokihara; Noboru Yamamoto; Ikuo Sekine; Hideo Kunitoh; Yuichiro Ohe; Emiko Ohki; Junichi Hashimoto; Tomohide Tamura |
Publication Detail:
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Type: Clinical Trial, Phase I; Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-14 |
Journal Detail:
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Title: Cancer science Volume: 101 ISSN: 1349-7006 ISO Abbreviation: Cancer Sci. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-23 Completed Date: 2010-03-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101168776 Medline TA: Cancer Sci Country: England |
Other Details:
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Languages: eng Pagination: 188-95 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antineoplastic Combined Chemotherapy Protocols / adverse effects, therapeutic use* Carboplatin / administration & dosage Carcinoma, Non-Small-Cell Lung / drug therapy* Female Humans Lung Neoplasms / drug therapy* Male Middle Aged Oligodeoxyribonucleotides / administration & dosage*, adverse effects, pharmacokinetics Paclitaxel / administration & dosage Toll-Like Receptor 9 / antagonists & inhibitors* |
| Chemical | |
Reg. No./Substance:
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0/Oligodeoxyribonucleotides; 0/ProMune; 0/Toll-Like Receptor 9; 33069-62-4/Paclitaxel; 41575-94-4/Carboplatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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