| 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. | |
| | |
MedLine Citation:
|
PMID: 21465314 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
P Schöffski; H Dumez; R Ruijter; B Miguel-Lillo; A Soto-Matos; V Alfaro; G Giaccone |
Related Documents
:
|
743694 - Electrophysiological effects of verapamil. 189794 - Histochemical and histological effects of lead on the liver and kidney of the dog. 3664544 - Autonomic modulation of aminophylline influence on the electrophysiological effects of ... 20035864 - The pharmacokinetics of orally administered s-carboxymethyl-l-cysteine in the dog, calf... 2783184 - An alprostadil analogue and human gastric secretion. a double-blind placebo-controlled ... 7717584 - Cortical bone concentrations of enrofloxacin in dogs. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-4-5 |
Journal Detail:
|
Title: Cancer chemotherapy and pharmacology Volume: - ISSN: 1432-0843 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
|
Created Date: 2011-4-5 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7806519 Medline TA: Cancer Chemother Pharmacol Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Department of General Medical Oncology, University Hospitals Leuven, Leuven Cancer Institute, Catholic University Leuven, Herestraat 49, 3000, Leuven, Belgium, patrick.schoffski@uzleuven.be. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: t(11;18)(q21;q21) translocation as predictive marker for non-responsiveness to salvage thalidomide t...
Next Document: Evaluation of functional ability of rheumatoid arthritis based on HAQ score and BMD among South Indi...