Abstract .
In Vitro / In Vivo Data Whowed Synergism of Cisplatin and Lurbinectedin in Ovarian Cáncer 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 Advance Solid Tumors .
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 .
*.- 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 Oartial Response .
Disease Stabilization for ≥ 4 Months was Observed in 4 and 10 Patients, Respectively .
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 .