The safety of dose-dense liposomal-encapsulated doxorubicin in association with docetaxel (MyTax) in breast cancer.

Abstract

Abstract Abstract #2157 Background: Liposomal-Encapsulated Doxorubicin (LED) shows equivalent efficacy, better cardiac tolerability at higher cumulative dose than conventional anthracyclines in breast cancer treatment.
 Methods: Sixteen pts were enrolled in a dose-finding study of LED (TLC-D99 Myocet ®) associated to Docetaxel (TXT). Twelve pts were treated with a fixed TXT dose (50 mg/m2) and TLC-D99 at three dose levels, 40-45-50 mg/m2, days 1 and 15 every 2 weeks using an intra- and inter-patient approach; four pts wrere treated at the TLC-D99 recommended dose (50 mg/m2). Cardiac monitoring of LVEF was performed every two cycles; Precursor Brain Natriuretic Peptide (proBNP) and cardiac Troponin (c-TnI) before and after 24 h chemotherapy was evaluated.
 Results: Breast cancer (BC) disease extension: metastatic (MBC), 8; locally advanced BC, 5; T2-T3 BC, 3. Previous chemotherapy: untreated, 11 pts; adjuvant, 5 pts. Enrolled pts for each dose-level: I, 7; II, 9; III, 14. Newly treated pts: I dose-level, 7; II dose-level, 3; III dose-level, 6. Valuable cycles for each dose-level in a total 77 cycles: I, 14; II, 21; III, 42. DLTs were observed in 3 pts, 21%, and 3 cycles, 4%: 2 cardiac, characterized by a 19% LVEF decrease and a symptomatic arrhythmia; one G4 hematologic resistant to G-CSF. DLTs for each dose-level by pts and cycles, respectively: I, 14% (1/7 pts) and 7% (1/14 cycles); II, no DLT in 9 pts and 21 cycles; III, 14% (2/14 pts) and 5% (2/42 cycles). Cumulative G3-4 toxicities by pts and cycles, respectively: cardiac arrhythmia 6% and 1,3%, cardiac general (symptomatic LVEF decrease), 6% and 1,3%; alopecia 81% and 65%; neutropenia resistant to G-CSF, 6% and 1,3%. Cardiac DLTs were observed in 2 elderly pts (>65 y). The 2 cardiac DLTs were observed in 2 out of 3 pts with pre-existing diastolic dysfunction. No pathologic increase of c-TnI levels was detected. Seven pts showed increased pro-BNP after chemotherapy; 1 of these with increased pro-BNP after chemotherapy, persistent the day 1 of each subsequent chemotherapy showed a DLT;
 G2 toxicities by patients and cycles, respectively: asthenia 37% and 18%, stomatitis/mucositis 12% and 5%, nausea 31% and 12%. Median rDI of TLC-D99 was 25 mg/m2/w and TXT 25 mg/m2/w for pts, respectively. Preliminary efficacy in 16 assessable pts: LA-BC and MBC, 1 CR (pCR) 7 PR (OR 62%), 4 SD and 1 PD; T2-T3 BC, 2 PR and 1 SD.
 Conclusion: dose-dense TLC-D99/Docetaxel association can be safely recommended at the dose of 50 mg/m2 for each drug. Docetaxel intensification is ongoing. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2157.