Phase I combination study of trabectedin and capecitabine in patients with advanced malignancies
| Autor: | D. Cleere, S. Eppers, E. Rivera, Lia Gore, J. Li, S. L. Moulder-Thompson, Cindy L. O'Bryant, Michele Basche, S. G. Eckhardt, S. Grolnic, Y. A. Elsayed |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Maximum Tolerated Dose Nausea Dioxoles Neutropenia Deoxycytidine Gastroenterology Drug Administration Schedule Capecitabine Young Adult Refractory Pharmacokinetics Neoplasms Tetrahydroisoquinolines Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Pharmacology (medical) Adverse effect Trabectedin Aged Pharmacology Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Clinical trial Oncology Anesthesia Female Fluorouracil medicine.symptom business medicine.drug |
| Zdroj: | Investigational New Drugs. 30:1942-1949 |
| ISSN: | 1573-0646 0167-6997 |
| DOI: | 10.1007/s10637-011-9747-9 |
| Popis: | Background To determine the maximum tolerated dose (MTD), safety and pharmacokinetics of trabectedin with capecitabine in patients with advanced malignancies. Design In this Phase I, open-label, dose-finding study, patients refractory to standard therapy received trabectedin (3-h intravenous infusion, 0.4–1.3 mg/m2, day 1) and capecitabine (2,000 or 1,600 mg/m2/day orally, days 2–15) every 3 weeks. Standard “3 + 3” dose escalation was used to define the MTD. Antitumor response was assessed every two cycles; adverse events (AEs) were recorded throughout. Results Forty patients received 149 cycles of treatment (median 2; range 1–11) at nine dose levels. Gastrointestinal dose-limiting toxicities in two patients at two dose levels with capecitabine at 2,000 mg/m2/day prompted dose reduction to 1,600 mg/m2/day and initiation of new trabectedin dose escalation at 0.6 mg/m2. The MTD was capecitabine 1,600 mg/m2/day + trabectedin 1.1 mg/m2. Common grade 3–4 drug-related AEs were neutropenia (20%), nausea (18%), diarrhea (15%) and palmar-plantar erythrodysesthesia (15%). One patient with cholangiocarcinoma achieved a sustained partial response, and 18 patients maintained stable disease (six for ≥6 months). Conclusions The combination of trabectedin and capecitabine is generally well tolerated, without pharmacokinetic interactions, and shows some activity in patients with advanced cancers. |
| Databáze: | OpenAIRE |
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