Phase I dose escalation and PK study of thermally sensitive liposomes containing doxorubicin given during radiofrequency ablation (RFA) in patients with non-resectable primary and metastatic liver cancer

15010 Purpose: This phase I dose escalation and pharmacokinetic (PK) study in patients with non-resectable primary or metastatic hepatic tumors undergoing radiofrequency ablation (RFA) uses a 30-minute IV infusion of ThermoDox (TDox) starting 15 minutes prior to RFA treatment. TDox liposomes are engineered to release doxorubicin (Dox) locally at temperatures greater than 39.5 °C. High local concentrations of Dox could allow for increased drug concentration targeted at the tumor margins in an effort to achieve improved local recurrence and tumor control near these RFA-induced thermal lesions. The phase I study goals are to determine the maximum tolerated dose and dose-limiting toxicity of TDox. Patients and Methods: Patients (pts) must be eligible for RFA for primary (HCC) or metastatic liver cancer (MLC). Main inclusion criteria are = 4 lesions and = 7 cm in greatest diameter. Dose escalation is: cohorts of 3–6 pts treated with a single dose of 20, 30, 40, 50, 60 or 70 mg/m2. RFA is administered via percutaneous or surgical approach. RFA treatment without TDox can be repeated for recurrent hepatic (distant or local) tumors. Patients requiring systemic chemotherapy following RFA are removed from the study. MRI, PET and contrast enhanced CT (CE-CT) scans are done pre-, one and three months post-treatment (q3 months thereafter for patients on trial). CE-CT scans are also performed immediately following RFAs. Patients are assessed for safety, PK, and lesion diameters on CT. RFA+TDox lesion diameters will be compared to patients treated by RFA alone (control) at the same institution. Results: A total of 22 pts have been treated as of January 2007 submission date (3, 6, 6, 6, 1 patients at 20, 30, 40, 50, and 60 mg/m2, respectively). This population includes 8 pts with HCC and 14 pts with MLC. Grade 3/4 toxicity (reversible neutropenia) has been observed to be dose dependent. 1 patient at 50 mg/m2 has met DLT criteria. Conclusions: TDox has been safely administered in combination with percutaneous or surgical RFA procedures in 22 patients with liver tumors. There has been limited, manageable toxicity thus far. Enrollment continues as the MTD and DLT have yet to be defined. [Table: see text]