A phase I/IIa clinical trial of CLAOP21 and CLAOP14 in patients with high grade non-Hodgkins lymphoma and cardiac risk factors

Abstract

17548 Background: CHOP combination chemotherapy is the most effective and least toxic regimen for high-grade Non-Hodgkin’s-lymphoma (NHL). Doxorubicin, however, presents a problem in patients at risk for cardiotoxicity. Pegliposomal doxorubicin is a liposomal preparation of doxorubicin with minimal cardiotoxicity. In the CLAOP regimen reported here, we substituted conventional doxorubicin in the CHOP regimen by pegliposomal doxorubicin. Methods: An open-label phase I/IIa study was performed evaluating CLAOP21/20 with 20 mg/m2 of pegliposomal doxorubicin every 21 days, and a dose-dense CLAOP14 regimen supported by G-CSF or pegylated G-CSF every 14 days with escalating doses of pegliposomal doxorubicin in elderly high-grade lymphoma patients. Results: A total of 12 patients were enrolled for CLAOP 21/20, and 24 patients for CLAOP 14/20. CLAOP21/20 was well tolerated with a degree of hematotoxicity similar to that reported with regular CHOP. In the CLAOP14 cohort, a trend towards cumulative hematotoxicity. Palmar plantar erythema (PPE) exceeding grade II and other non-hematological toxicities exceeding grade I, except of alopecia, were not observed. A pegliposomal doxorubicin dose of 25 mg/m2 (CLAOP14/25) was associated with dose-limiting haematotoxicity, febrile episodes, and PPE. Both, the 3-weekly and the 2-weekly regimens were active with an overall response rate of 60% and 77%, respectively. Cardiotoxicity attributable to doxorubicin was not observed in any patient. Conclusions: The recommended dose of pegliposomal doxorubicin in the biweekly CLAOP regimen for Phase II/III testing is 20 mg/m2, a regimen that can safely be administered to old patients without apparent cardiotoxicity. [Table: see text]