A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials Journal Article
| Authors: | Le Cesne, A.; Yovine, A.; Blay, J. Y.; Delaloge, S.; Maki, R. G.; Misset, J. L.; Frontelo, P.; Nieto, A.; Jiao, J. J.; Demetri, G. D. |
| Article Title: | A retrospective pooled analysis of trabectedin safety in 1,132 patients with solid tumors treated in phase II clinical trials |
| Abstract: | Purpose To summarize the safety experience obtained from phase II clinical trials conducted with trabectedin as single-agent therapy in patients with advanced solid tumors. Methods This retrospective analysis includes 1,132 patients exposed to trabectedin in 19 phase II trials carried out between February 1999 and April 2008. Trabectedin was administered intravenously as 1 of 3 schedules: 24-hour infusion every 3 weeks (q3wk 24-h; n=570/2,818 cycles), 3-hour infusion every 3 weeks (q3wk 3-h; n=258/1,003 cycles), and 3-hour infusion for three consecutive weeks every 4 weeks (qwk 3-h; n=304/1,198 cycles). Results The majority of patients (90%) had received previous chemotherapy. Patients were given a median of three treatment cycles of trabectedin (range, 1-59). Nausea, fatigue and vomiting were the most common trabectedinrelated adverse events, reported in =20% of patients. Reversible myelosuppression (mainly neutropenia) and transient reversible transaminase increases were the most common laboratory abnormalities seen with trabectedin, with a very low incidence of relevant clinical consequences. Deaths associated with drug-related adverse events were infrequent, occurring in 19 (1.7%) patients. Conclusion Single-agent trabectedin treatment was reasonably well tolerated. Trabectedin can be administered for prolonged periods to patients with sustained clinical benefit (induction of disease stability or shrinkage) without cumulative toxicities over time. © 2012 Springer Science+Business Media, LLC. |
| Keywords: | osteosarcoma; adolescent; adult; cancer chemotherapy; child; controlled study; school child; aged; aged, 80 and over; middle aged; primary tumor; young adult; major clinical study; drug tolerability; fatigue; neutropenia; advanced cancer; dose response; drug dose comparison; drug dose reduction; drug efficacy; drug safety; drug withdrawal; side effect; solid tumor; treatment duration; outcome assessment; endometrium cancer; neoplasms; colorectal cancer; gastrointestinal stromal tumor; melanoma; infection; liver toxicity; multiple cycle treatment; nephrotoxicity; ovary cancer; sensory neuropathy; breast cancer; bone marrow suppression; blood toxicity; heart disease; lung non small cell cancer; mucosa inflammation; stomatitis; thrombocytopenia; peripheral neuropathy; drug effect; retrospective study; ewing sarcoma; fever; drug fatality; disease severity; adverse outcome; dosage schedule comparison; antineoplastic agents, alkylating; clinical evaluation; blood transfusion; soft tissue sarcoma; safety; drug monitoring; clinical effectiveness; kidney cancer; trabectedin; leiomyosarcoma; alopecia; phase ii; liposarcoma; rhabdomyolysis; dioxoles; et-743; yondelis; extravasation; tetrahydroisoquinolines; bleeding disorder; singleagent; chemotherapy induced nausea and vomiting; alanine transaminase |
| Journal Title: | Investigational New Drugs |
| Volume: | 30 |
| Issue: | 3 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2012-06-01 |
| Start Page: | 1193 |
| End Page: | 1202 |
| Language: | English |
| DOI: | 10.1007/s10637-011-9662-0 |
| PROVIDER: | scopus |
| PUBMED: | 21484250 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2012" - "CODEN: INNDD" - "Source: Scopus" |
