Purpose Thiotepa is used in high-dose chemotherapy (HDT) before autologous hematopoietic stem cell transplantation (HSCT) to treat solid tumors and hematological malignancies. This Phase 1 study was conducted to establish the pharmacokinetics (PK) of thiotepa in a Japanese population. Methods HDT/HSCT was performed in pediatric patients (≥ 2 years) with solid tumors or brain tumors (thiotepa 200 mg/m 2 /day IV-infused over 24 h on HSCT Days − 12, − 11, − 5, and − 4 and melphalan 70 mg/m 2 /day IV-infused over 1 h on Days − 11, − 5, and − 4) and adult patients (≥ 16 years) with malignant lymphoma (thiotepa 200 mg/m 2 /day 2-h IV-infusion on HSCT Days − 4 and − 3 plus busulfan 0.8 mg/kg 2-h IV-infusion every 6 h from HSCT Days − 8 to − 5). Pharmacokinetics of thiotepa were assessed following initial dose. Safety and efficacy were also evaluated. Results Nine pediatric and 10 adult patients were enrolled. Mean volume of distribution ( V z ) of thiotepa normalized with body surface area (BSA) was lower for pediatric patients (16.4 L/m 2 ) compared with adult patients (26.4 L/m 2 ) as expected due to the higher specific surface area of children. Clearance and biological half-life were similar between pediatric and adult patients. Two serious adverse events (cardiac arrest and pulmonary edema) were observed. Survival rate (Day 100 post-HSCT) was 77.8% (95% CI 36.5–93.9%) for pediatric patients and 100% for adult patients. Conclusion Thiotepa elimination was comparable in pediatric and adult patients with cancer. Lower V z in pediatric compared with adult patients was expected. HDT with thiotepa prior to autologous HSCT was well tolerated. Study registration Japic CTI-163433. Electronic supplementary material The online version of this article (10.1007/s00280-019-03914-2) contains supplementary material, which is available to authorized users.
【저자키워드】 pharmacokinetics, HSCT, TEPA, Thiotepa,