We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Spisulosine (ES-285) given as a weekly three-hour intravenous infusion: results of a phase I dose-escalating study in patients with advanced solid malignancies.
- Authors
Schöffski, P.; Dumez, H.; Ruijter, R.; Miguel-Lillo, B.; Soto-Matos, A.; Alfaro, V.; Giaccone, G.
- Abstract
Purpose: Spisulosine is a marine compound that showed antitumor activity in preclinical studies. We report results of a phase I trial performed in patients with advanced solid tumors with the marine compound, with the aim to determine the maximum tolerated dose (MTD) of a weekly 3-h intravenous (iv.) infusion, and to evaluate the safety, efficacy, and pharmacokinetics (PK) of the compound. Patients and methods: Two centers contributed 25 patients to the trial, and 7 dose levels were explored. Results: In dose levels ranging from 4 to 128 mg/m²/day, no dose-limiting toxicities (DLT) were observed. One patient had DLT at 200 mg/m², a reversible grade 3 ALT increase. The MTD was not reached due to early termination of the Spisulosine trial program but is considered to be likely in the range of 200 mg/m² for this schedule. Drug-related adverse reactions included mild to moderate nausea, pyrexia, injection site reactions, and vomiting. One case of grade 4 peripheral motor and sensory neuropathy associated with general weakness and pain was observed during treatment cycle 4 and possibly contributed to the death of the patient. Grade 3 laboratory abnormalities included anemia and lymphopenia and increases in liver enzymes (alkaline phosphatase, transaminases, and bilirubin). Objective responses were not observed, and only four patients had short-lasting stable disease (<3 months). The PK data indicated a wide distribution, a long residence time, and dose proportionality of the agent. Conclusions: Hepato- and neuro-toxicity are schedule independent dose-limiting adverse events for this marine compound, as illustrated by this and other early clinical trials.
- Subjects
TUMOR treatment; ANTINEOPLASTIC agents; INTRAVENOUS therapy; PHARMACOKINETICS; NEUROTOXICOLOGY; CLINICAL trials; HEPATOTOXICOLOGY
- Publication
Cancer Chemotherapy & Pharmacology, 2011, Vol 68, Issue 6, p1397
- ISSN
0344-5704
- Publication type
Academic Journal
- DOI
10.1007/s00280-011-1612-1