Phase I study of trabectedin (T) in combination with docetaxel (D) in patients with advanced malignancies

Autor: M. von Mehren, D. Buck, Yusri A. Elsayed, E. Temmer, Roger B. Cohen
Rok vydání: 2006
Předmět:
Zdroj: Journal of Clinical Oncology. 24:2068-2068
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2006.24.18_suppl.2068
Popis: 2068 Background: T is a novel cytotoxic agent that binds to the DNA minor groove and is active in several tumor types. The objective of this study is to determine the maximum tolerated dose (MTD) of the combination. Other objectives include safety and efficacy. Methods: Eligible patients (pts) had advanced cancer, PS 0–1 and adequate organ function. Restricted pts were limited to 1 prior cytotoxic regimen, while unrestricted pts had no limit. On day 1 of each cycle, Pts received D starting at 60 mg/m2 over 1 hour followed by T starting at 0.4 mg/m2 over 3 hours. Dosing was repeated q 3 weeks. Incremental doses of both drugs were explored. PK samples were collected. A standard “3+3” dose escalation, definitions of dose limiting toxicity (DLT), and dose modifications were implemented. Results: To date, 31 pts have been treated, receiving 147 cycles (Range 1–28, median 6). At dose level 2 (D 60 mg/m2 + T 0.6 mg/m2), 2/4 unrestricted pts and 3/5 restricted pts developed DLT (grade IV neutropenia and/or febrile neutropenia) requiring institution of prophylactic filgrastim. Therapy was well tolerated after institution of filgrastim and no DLTs have been observed through the current dose level 6 (D 60 mg/m2 + T 1.3 mg/m2). Most frequently related grade 3 and 4 adverse events (AE) were: neutropenia (51%), elevated liver enzymes (3.7%), DVT (3.7%), and hyponatremia (3.7%). The most frequently related grade 1and 2 AEs were: fatigue (56%), neutropenia (56%), nausea (55%), and anemia (40%). Anti-tumor activity included a complete response in a pt with peritoneal Ca and durable prolong stable disease (SD) in 2 pts with sarcoma (20 + and 10 + months) and a pt with prostate Ca (8+ months). Another pt with gastric Ca achieved SD lasting 8 months. PK evaluations of D and T are ongoing. Conclusions: The combination of T and D with filgrastim support is safe and well-tolerated. Preliminary data suggest that this regimen is active in pts with advanced cancers. Additional cohorts are planned giving D 75 mg/m2 and T 1.3 mg/m2. [Table: see text]
Databáze: OpenAIRE
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