Phase I dose-escalation study of cabazitaxel administered in combination with cisplatin in patients with advanced solid tumors.

摘要: Introduction Cabazitaxel is a second-generation taxane with in vivo activity against taxane-sensitive and -resistant tumor cell lines xenografts. Cabazitaxel/cisplatin have therapeutic synergism tumor-bearing mice, providing rationale for assessing this combination patients solid tumors. Methods The primary objectives of study were to determine dose-limiting toxicities (DLTs) the maximum tolerated dose (MTD) cabazitaxel/cisplatin combined regimen (Part 1) assess antitumor at MTD 2). Safety pharmacokinetics (PK) also examined. Results Twenty-five advanced tumors enrolled (10 Part 1; 15 In 1, two levels evaluated; (given Q3W) was 15/75 mg/m2. DLTs occurring during Cycle 1 administered (20/75 mg/m2; acute renal failure febrile neutropenia) (febrile neutropenia hypersensitivity despite pre-medication) as expected taxane/platinum combinations. For 18 treated MTD, most frequent possibly related non-hematologic treatment-emergent adverse events (Grade ≥3) nausea (16.7 %), fatigue, decreased appetite (each 11.1 %). Neutropenia Grade ≥3 hematologic laboratory abnormality (77.8 best overall response stable disease, observed 66.7 % patients. PK results did not appear differ from single-agent administration each agent. Conclusion Combination treatment had manageable safety profile; no interactions evident. recommended Phase II mg/m2 every 3 weeks. Antitumor findings suggest that further evaluation disease-specific trials warranted.