Details

Autor(en) / Beteiligte

• Jimeno, Antonio
• Sharma, Manish R.
• Szyldergemajn, Sergio
• Gore, Lia
• Geary, David
• Diamond, Jennifer R.
• Fernandez Teruel, Carlos
• Soto Matos-Pita, Arturo
• Iglesias, Jorge Luis
• Cullell-Young, Martin
• Ratain, Mark J.

Titel

Phase I study of lurbinectedin, a synthetic tetrahydroisoquinoline that inhibits activated transcription, induces DNA single- and double-strand breaks, on a weekly × 2 every-3-week schedule

Ist Teil von

• Investigational new drugs, 2017-08, Vol.35 (4), p.471-477

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2017

Quelle

SpringerLink

Beschreibungen/Notizen

• Summary Background Lurbinectedin administered as a 1-h intravenous infusion every 3 weeks induces neutropenia, with the nadir usually occurring during the second week. This phase I study evaluated an alternative lurbinectedin dosing schedule consisting of a 1-h infusion on days 1 and 8 every 3 weeks. Patients and methods Twenty-one patients with advanced cancer received lurbinectedin using a standard cohort dose escalation design. Results Three dose levels of 3, 4, and 5 mg of lurbinectedin were explored. The recommended phase II dose was 5 mg, with 3 of 13 patients having dose-limiting toxicity (DLT), although grade 4 neutropenia occurred in 50% of patients. Other frequent toxicities were mild to moderate nausea and vomiting, fatigue, decreased appetite, stomatitis and asymptomatic creatinine and transaminase increases. No objective responses occurred, but prolonged stable disease was observed in 7 patients, including 3 with soft tissue sarcoma. Conclusion The recommended phase II dose of lurbinectedin is 5 mg, administered as a 1-h infusion on days 1 and 8 every 3 weeks. These data support further testing of this dose and schedule, particularly in soft tissue sarcoma.