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Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 1991; Vol. 29 (2), pp. 145-9. - Publication Year :
- 1991
-
Abstract
- Didemnin B (NSC 325,319), a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m2 was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 min every 28 days. In the current study, 30 patients presenting with previously treated non-small-cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m2. Neuromuscular toxicity was dose-limiting. Nausea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premedication regimen. In all, 2 minor responses were seen among 24 evaluable patients. Because neuromuscular toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, following the premedication of patients with antiemetics.
- Subjects :
- Adult
Aged
Antineoplastic Agents administration & dosage
Drug Administration Schedule
Drug Evaluation
Female
Humans
Infusions, Intravenous
Male
Middle Aged
Neuromuscular Junction drug effects
Peptides, Cyclic administration & dosage
Antineoplastic Agents adverse effects
Carcinoma, Non-Small-Cell Lung drug therapy
Depsipeptides
Lung Neoplasms drug therapy
Muscles drug effects
Peptides, Cyclic adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 0344-5704
- Volume :
- 29
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 1662119
- Full Text :
- https://doi.org/10.1007/BF00687325