Abstract
Purpose
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.
Patients and methods
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 μg/m2. PK parameters of SJG-136 were assessed following the intravenous administration of SJG-136 on days 1 and 15 of cycle 1.
Results
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 μg/m2/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.
Conclusion
For patients with advanced solid tumors, the MTD of SJG-136 is 40 μg/m2/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.
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Supported by CTEP, NIH 5U01CA069856-15; NCI-sponsored trial # 6818.
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Janjigian, Y.Y., Lee, W., Kris, M.G. et al. A phase I trial of SJG-136 (NSC#694501) in advanced solid tumors. Cancer Chemother Pharmacol 65, 833–838 (2010). https://doi.org/10.1007/s00280-009-1088-4
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DOI: https://doi.org/10.1007/s00280-009-1088-4