Phase I study of weekly plitidepsin as 1-hour infusion combined with carboplatin in patients with advanced solid tumors or lymphomas.

Abstract

This dose-escalating phase I clinical trial was designed to determine the recommended dose (RD) and to assess the safety and feasibility of weekly plitidepsin (1-hour i.v. infusion, Days 1, 8 and 15) combined with carboplatin (1-hour i.v. infusion, Day 1, after plitidepsin) in 4-week (q4wk) cycles given to patients with advanced solid tumors or lymphomas. Twenty patients were enrolled and evaluable for both safety and efficacy. The starting dose was plitidepsin 1.8 mg/m(2) and carboplatin area under the curve (AUC) = 5 min*mg/ml; dose escalation proceeded based on worst toxicity in the previous cohort. The maximum tolerated dose (MTD) was plitidepsin 3.0 mg/m(2) and carboplatin AUC = 5 min*mg/ml, with grade 3 transaminase increases as the most common dose-limiting toxicities (DLTs). The RD for phase II studies was plitidepsin 2.4 mg/m(2) and carboplatin AUC = 5 min*mg/ml, with fatigue, myalgia and nausea as the most common drug-related adverse events (AEs). No unexpected toxicity was seen. Twelve patients (60%), ten of whom were heavily pretreated (≥2 previous chemotherapy lines) showed stable disease (SD), with a median time to progression (TTP) of 4.4 months. In conclusion, plitidepsin 2.4 mg/m(2) and carboplatin AUC = 5 min*mg/ml is a safe dose for future phase II studies evaluating the use of this combination in cancer patients potentially sensitive to platinum-based therapy.

• Authors: Ramón Salazar, Ruth Plummer, Ana Oaknin, Angela Robinson, Beatriz Pardo, Arturo Soto-Matos, Alejandro Yovine, Sergio Szyldergemajn, Alan Hilary Calvert
• Journal: Investigational new drugs (Invest New Drugs) Vol. 29 Issue 6 Pg. 1406-13 (Dec 2011) ISSN: 1573-0646 [Electronic] United States
• PMID: 20623160 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Depsipeptides
• Peptides, Cyclic
• Carboplatin
• plitidepsin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Area Under Curve
• Carboplatin (administration & dosage)
• Depsipeptides (administration & dosage)
• Dose-Response Relationship, Drug
• Female
• Humans
• Infusions, Intravenous
• Lymphoma (drug therapy, pathology)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy, pathology)
• Peptides, Cyclic
• Treatment Outcome