Abstract P6-13-15: Lyso-thermosensitive liposomal doxorubicin shows efficacy with minimal adverse events in patients with breast cancer recurrence at the chest wall
Authors: Rugo H , Pabbathi H , Shrestha S , Aithal S , Borys N , Musso L , Zoberi I 
Published: May 2016

Abstract
INTRODUCTION: Local-regional recurrence after definitive treatment of breast cancer is reported in 5 – 40 % of patients depending risk factors and initial treatment. Chest wall recurrence is associated with poor quality of life and limited treatment options. Lyso-thermosensitive liposomal doxorubicin (LTLD, Thermodox®) is an intravenously administered agent designed to selectively release doxorubicin when exposed to temperatures ≥39.5° C at a targeted tumor. Hyperthermia, the elevation of tissue temperature in the range of 40° C to 44° C, causes direct cytotoxicity, enhanced blood flow, and oxygenation. We are reporting the interim findings of an ongoing Phase I/II Study Evaluating the Maximum Tolerated Dose, Bioequivalence/Pharmacokinetics, Safety, and Efficacy of LTLD in Patients with Local-Regional Recurrent Breast Cancer. Final results will be presented in December.
METHODS: Patients with breast carcinoma on the chest wall with progression following radiation were eligible; prior chemotherapy and hormone therapy were allowed. LTLD was administered intravenously followed immediately by hyperthermia in up to two treatment fields for 1 hour per field for a goal of 40–42°C. Response was measured using clinical assessment, CT, and digital photos. All subjects were assessed for safety. Up to six cycles of LTLD/hyperthermia were administered depending on disease progression or tolerance. A total of 11 patients were enrolled on the Phase I portion of the study and 9 were evaluable for efficacy review. To date, 17 patients are enrolled on the Phase II portion of the study and 13 are evaluable for efficacy review. Once 12 patients are found to be evaluable for PK the primary endpoint of bioequivalence can be evaluated.
RESULTS: A dose of 50 mg/m2 was recommended by the DSMB at completion of the Phase I study. Seven subjects were dosed at 50mg/m2, two patients developed a localized reaction in the treatment area consisting of erythema, woody induration, and pain which resolved with discontinuation of treatment. Twenty patients were dosed at 40mg/m2 without recurrence of symptoms. To date, twenty-eight patients were enrolled in the phase I/II study; one subject was excluded due to dose modification following 2 cycles of ThermoDox at a dose of 50mg/m2 to 40mg/m2 at cycle 3. This subject had a durable partial response. The tables summarize the safety and efficacy data. All efficacy data is investigator reported.
Combined Phase I/II Safety DataSafety Data40 mg/m2 (N=20)50 mg/m2 (N=7)Any AE Event (n, %)17 85.07 100.0Grade 3+ AE (n, %)10 50.06 85.7Serious AE (n, %)5 25.03 42.9Hematological AE (n, %)10 50.07 100.0Deaths due to AE (n, %)0 0.00 0.0
Combined Phase I/II Efficacy DataEfficacy Data40 mg/m2 (N=20)50 mg/m2 (N=7)Responders (Partial & Complete) (n, %)10 50.03 42.9Complete Response (n, %)5 25.01 14.3Partial Response (n, %)5 25.02 28.6Durable Response (lasting ≥ 3 months) (n, %)3 15.00 0.0
CONCLUSION: These findings suggest that LTLD at a dose of 40 mg/m2 combined with hyperthermia offers a promising and well tolerated treatment option for patients with recurrent chest wall disease from breast cancer. Additional data will be presented based on full trial accrual.
Citation Format: Rugo H, Pabbathi H, Shrestha S, Aithal S, Borys N, Musso L, Zoberi I. Lyso-thermosensitive liposomal doxorubicin shows efficacy with minimal adverse events in patients with breast cancer recurrence at the chest wall. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-13-15.