A phase I trial of SJG-136 (NSC#694501) in advanced solid tumors Journal Article
| Authors: | Janjigian, Y. Y.; Lee, W.; Kris, M. G.; Miller, V. A.; Krug, L. M.; Azzoli, C. G.; Senturk, E.; Calcutt, M. W.; Rizvi, N. A. |
| Article Title: | A phase I trial of SJG-136 (NSC#694501) in advanced solid tumors |
| Abstract: | SJG-136 is a pyrrolobenzodiazepine dimer that forms DNA crosslinks and has demonstrated broad antitumor activity. We undertook this trial to determine the maximum-tolerated dose (MTD), toxicities and pharmacokinetic (PK) profile of SJG-136 in patients with an advanced solid tumor. In this phase I study, patients were treated with SJG-136 on days 1, 8 and 15 of a 28-day cycle. Dose levels studied were 10, 20, 40 and 60 mu g/m(2). PK parameters of SJG-136 were assessed following the intravenous administration of SJG-136 on days 1 and 15 of cycle 1. Twenty-one patients with advanced solid tumors were treated. Patients had a median of two prior chemotherapy regimens. Fatigue was dose-limiting with SJG-136 60 mu g/m(2)/day administered on days 1, 8 and 15 of a 28-day cycle. Grade 3 thrombocytopenia and delayed onset liver toxicity were seen in one patient each. PK parameters of SJG-136 indicated dose-proportional increases in systemic exposure with increasing doses. No objective responses were seen. For patients with advanced solid tumors, the MTD of SJG-136 is 40 mu g/m(2)/day administered on days 1, 8 and 15 of a 28-day cycle. The major dose limiting toxicity was fatigue. Alternative dosing strategies are now being evaluated. |
| Keywords: | lung cancer; solid tumors; phase i; inhibition; sjg-136; spectrum antitumor-activity; cross-linking agent; dna-binding; potent; nsc-694501; vitro |
| Journal Title: | Cancer Chemotherapy and Pharmacology |
| Volume: | 65 |
| Issue: | 5 |
| ISSN: | 0344-5704 |
| Publisher: | Springer |
| Date Published: | 2010-04-01 |
| Start Page: | 833 |
| End Page: | 838 |
| Language: | English |
| ACCESSION: | ISI:000274655500003 |
| DOI: | 10.1007/s00280-009-1088-4 |
| PROVIDER: | wos |
| PUBMED: | 19672598 |
| PMCID: | PMC3711187 |
| Notes: | --- - Article - "Source: Wos" |
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