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- Title
Phase I trial of non-cytotoxic suramin as a modulator of docetaxel and gemcitabine therapy in previously treated patients with non-small cell lung cancer.
- Authors
Lam, Elaine T.; Au, Jessie L.-S.; Otterson, Gregory A.; Wientjes, M. Guillaume; Ling Chen; Shen, Tong; Yong Wei; Xiaobai Li; Bekii-Saab, Tanios; Murgo, Anthony J.; Jensen, Rhonda R.; Grever, Michael; Villalona-Calero, Miguel A.
- Abstract
Purpose: In preclinical models, non-cytotoxic suramin (concentrations <50 μM) potentiates the activity of multiple chemotherapeutic agents. The present study evaluated the safety and tolerability of suramin in combination with docetaxel or gemcitabine in previously chemotherapy-treated patients with advanced non-small cell lung cancer. Methods: Patients received suramin intravenously in combination with either docetaxel on day 1 or gemcitabine on days 1 and 8, of each 21-day treatment cycle. After 3 cycles, patients with partial response (PR) or better continued on the same combination, whereas patients with stable disease (SD) or worse crossed-over to the other combination. Pharmacokinetic analyses were performed before and after each treatment. Results: Eighteen patients received a total of 79 courses (37 suramin plus docetaxel, 42 suramin plus gemcitabine). The dose-limiting toxicity (DLT) was febrile neutropenia, observed in three of six patients treated with suramin and docetaxel 75 mg/m. No DLTs were observed with suramin plus docetaxel 56 mg/m or suramin plus gemcitabine 1,250 mg/m. Common adverse events included neutropenia, thrombocytopenia, anemia, fatigue, nausea, vomiting, skin rash, hyperglycemia, and electrolyte abnormalities. The target plasma suramin concentration range of 10-50 μM was achieved in 90% of treatments. Discernable antitumor activity was noted in 11 patients (2 PR, 9 SD). Conclusions: Non-cytotoxic suramin, in combination with docetaxel 56 mg/m or gemcitabine 1,250 mg/m, was reasonably well-tolerated with a manageable toxicity profile. Target plasma concentrations were correctly predicted by our previously described dosing nomogram. The observed preliminary evidence of antitumor activity encourages evaluation of this strategy in efficacy trials.
- Subjects
ANTINEOPLASTIC agents; DRUG therapy; LUNG cancer; MEDICAL research; QUANTITATIVE research
- Publication
Cancer Chemotherapy & Pharmacology, 2010, Vol 66, Issue 6, p1019
- ISSN
0344-5704
- Publication type
Article
- DOI
10.1007/s00280-010-1252-x