Targeted liposomal daunorubicin (LDauno) dose escalation is feasible with filgrastim (F): Improved tumor response in colon cancer (CoC), prostate cancer (PrC), and non-small cell lung cancer (NSCLC)

Abstract

2107 Background: In animal models, response to targeted LDauno (DaunoXome) is dose dependent. DE has not been possible with liposomal doxorubicin due to cutaneous toxicity. In order to determine if DE is possible with LDauno, a DE study was performed in patients (pt) with stage 4 CoC, PrC, or NSCLC. Methods: Pts were eligible if they had 0–1 prior chemotherapy regimen, no significant hematologic, cardiac, or hepatorenal dyusfunction, and ps>60. Pt received LDauno IV Q3wk starting at 100 mg/m2 (NSCLC, CoC) or 80 mg/m2 (PrC), doses escalated by 20 mg/m2 after 2 cycles with no dose limiting toxicity (DLT), and initial doses escalated after no DLT in 3 pt per cohort. After LDauno, F was given at 5 mcg/kg daily for 10 d. Cardiac ejection fraction was measured at 0, 500, 750, and 1000 mg/m2 LDauno and at study completion. Toxicity was measured by SWOG criteria. Partial tumor response (PR) was defined as over 50% reduction in tumor area or PSA for at least 4 wk with improved symptoms and no new cancer. Results: 20/21 pt were evaluable. DLT grade 4 neutropenia (n) was observed in 4/5 and 5/6 pt at 140 and 150 mg/m2 LDauno. Duration of n was 3d or less and 2 pt had febrile n. Grade 4 thrombocytopenia was observed in 3/4 and 2/6 pt at 140 and 150 mg/m2. Other grade 3–4 adverse events were fatigue 5 pt, back pain 2, vomiting 1, dyspnea 2, dizziness 1, flushing 1, allergic reaction 1, confusion 1, hypokalemia 1, pneumothorax 1, and congestive heart failure 1. PR were observed in 1/8 CoC pt (duration 4 mo), 2/4 PrC (3,7 mo), and 2/9 NSCLC (3,5 mo). Improvements (>25%, <50%) were observed in 1/8 CoC (10 mo), 0/4 PrC, and 1/9 NSCLC (3 mo). Mean survival from time on study was 12.6 mo in CoC (range 6–19 mo), 8 mo in PrC (5–10), and 16.8 in NSCLC (2–84). Conclusions: We conclude that compared to standard dose LDauno of 80–100 mg/m2, DE up to 140 mg/m2 is feasible using standard dose F. Compared to historical controls, targeted LDauno may improve response rates and survival in previously treated CoC, PrC, and NSCLC. Targeted LDauno at escalated doses with F may be useful as a single agent or in combination with other drugs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Amgen