A phase I trial of lurbinectedin in combination with cisplatin in patients with advanced solid tumors.

ABSTRACT

Background In vitro/in vivo data showed synergism of cisplatin and lurbinectedin in ovarian cancer cells and grafts. This phase I trial investigated the recommended phase II dose (RD) of cisplatin and lurbinectedin combination, with (Group A) or without aprepitant (Group B), in patients with advanced solid tumors. Patients and Methods All patients received 60 mg/m2 cisplatin 90-min intravenous (i.v.) infusion followed by lurbinectedin 60-min i.v. infusion at escalating doses on Day 1 every 3 weeks (q3wk). Patients in Group A additionally received orally 125 mg aprepitant one hour before cisplatin on Day 1 and 80 mg on Days 2 and 3. Toxicity was graded according to the NCI-CTCAE v.4. Results RD for Group A was cisplatin 60 mg/m2 plus lurbinectedin 1.1 mg/m2. RD for Group B was cisplatin 60 mg/m2 plus lurbinectedin 1.4 mg/m2. The most frequent grade ≥ 3 adverse events were hematological [neutropenia (41%), lymphopenia (35%), leukopenia (24%), thrombocytopenia (18%)] and fatigue (35%) in Group A (n = 17), and neutropenia (50%), leukopenia (42%), lymphopenia (29%), and fatigue (13%) and nausea (8%) in Group B (n = 24). Four patients (2 in each group) had a partial response. Disease stabilization for ≥ 4 months was observed in 4 and 10 patients, respectively. Conclusion The combination of lurbinectedin with cisplatin was not possible in meaningful therapeutic dosage due to toxicity. The addition of aprepitant in combination with cisplatin did not allow increasing the dose due to hematological toxicity, whereas omitting aprepitant increased the incidence of nausea and vomiting. Modest clinical activity was observed in general.Clinical trial registration www.ClinicalTrials.gov code NCT01980667. Date of registration 11 November 2013.