363P - Breast cancer recurrences at the chest wall (BCRCW) when standard treatments (TX) have failed: lyso-thermosensitive liposomal doxorubicin (LTLD) + m...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Drug Development
Breast Cancer, Locally Advanced
Presenter Hope Rugo
Authors H.S. Rugo1, S.C. Formenti2, R.J. Myerson3, C.J. Diederich4, B.M. O'Connor5, A.J. Matzkowitz6, F. Muggia7
  • 1University of California, San Francisco, 94143 - /US
  • 2Radiation Oncology, NYU Langone Medical Center, 10016 - 4744/US
  • 3Radiation Oncology, Washington University School of Medicine in St. Louis, 63110 - 1010/US
  • 4Radiation Oncology, University of California, San Francisco, 94115 - 3024/US
  • 5Radiation Oncology, Commonwealth Atrius Cancer Center, 02190 - 3141/US
  • 6Radiation Oncology, Florida Cancer Specialists, 34655 - New Port Richey/US
  • 7Cancer Institute, NYU Langone Medical Center, 10016 - New York/US

Abstract

Background

BCRCW has a poor prognosis, with disfigurement, pain, and restriction of movement. Study treatment consisted of LTLD that releases high concentrations of doxorubicin (Dox) in areas treated with mild hyperthermia at > 39.5°C. MLH kills tumor cells, selectively increases liposomal permeability in tumor microvasculature, releases Dox from LTLD, and promotes Dox tumor uptake.

Methods

We conducted a phase I study of LTLD + MLH in patients (pts) with BCRCW tumors < 3 cm deep who had failed all standard Tx including surgery, radiation, and chemotherapy (CTx). Pts received up to 6 LTLD/MLH Txs every 21 days. Dosing cohorts started at 40 mg/m2 and stopped escalation at 50 mg/m2. LTLD was infused IV over 30 minutes (min); then MLH was given by microwave or ultrasound. The thermal dose goal was 40°C-42°C for 60 min. Pharmacokinetic samples for total plasma Dox and doxorubicinol (Doxol) were taken at 0.5, 5, 10 and 24 hours after starting infusion.

Results

Eleven pts with a median of 4 prior CTx (range 2 – 12) were enrolled; 10 had recurred after prior anthracycline (AC). All pts received > 2 cycles. The within subject variability in Dox and Doxol exposure was small with mean Cycle 2 vs Cycle 1 ratios ranging from 0.99 to 1.06.

Cmax/dose (ng/ml)/(mg/m2) DoxDoxol Cycle 1499.820.46 Cycle 2512.000.45
AUClast/dose ((ng*hr/ml)/(mg/m2) DoxDoxol 1,338.187.96 1,381.828.04

Two types of grade 3/4 toxicity were seen in > 5% of 42 cycles given: reversible neutropenia in 17 (40.5%) and reversible leukopenia in 9 (21.4%). One case (each) of mucositis (grade 1), chest wall thermal burn, and chest wall cellulitis (both grade 4) occurred, and no cases of cardiomyopathy or hand-foot toxicity were seen. The rate of clinically significant (> 6 point) QoL improvement on the FACT-B after 2 cycles was 54.5% (95% CI: 25.1% - 83.9%), including 1 lasting > 3 months. The local objective response rate was 45.5% (95% CI: 16.1% - 74.9%), with 1 complete and 4 partial local responses.

Conclusion

LTLD + MLH is safe and active in BCRCW pts with prior radiation and AC exposure. A phase II study is underway.

Disclosure

All authors have declared no conflicts of interest.