Two phase I dose-escalation/pharmacokinetics studies of low temperature liposomal doxorubicin (LTLD) and mild local hyperthermia in heavily pretreated patients with local regionally recurrent breast cancer.
Journal Article (Journal Article;Multicenter Study)
PURPOSE: Unresectable chest wall recurrences of breast cancer (CWR) in heavily pretreated patients are especially difficult to treat. We hypothesised that thermally enhanced drug delivery using low temperature liposomal doxorubicin (LTLD), given with mild local hyperthermia (MLHT), will be safe and effective in this population. PATIENTS AND METHODS: This paper combines the results of two similarly designed phase I trials. Eligible CWR patients had progressed on the chest wall after prior hormone therapy, chemotherapy, and radiotherapy. Patients were to get six cycles of LTLD every 21-35 days, followed immediately by chest wall MLHT for 1 hour at 40-42 °C. In the first trial 18 subjects received LTLD at 20, 30, or 40 mg/m2; in the second trial, 11 subjects received LTLD at 40 or 50 mg/m2. RESULTS: The median age of all 29 patients enrolled was 57 years. Thirteen patients (45%) had distant metastases on enrolment. Patients had received a median dose of 256 mg/m2 of prior anthracyclines and a median dose of 61 Gy of prior radiation. The median number of study treatments that subjects completed was four. The maximum tolerated dose was 50 mg/m2, with seven subjects (24%) developing reversible grade 3-4 neutropenia and four (14%) reversible grade 3-4 leucopenia. The rate of overall local response was 48% (14/29, 95% CI: 30-66%), with. five patients (17%) achieving complete local responses and nine patients (31%) having partial local responses. CONCLUSION: LTLD at 50 mg/m2 and MLHT is safe. This combined therapy produces objective responses in heavily pretreated CWR patients. Future work should test thermally enhanced LTLD delivery in a less advanced patient population.
Full Text
Duke Authors
Cited Authors
- Zagar, TM; Vujaskovic, Z; Formenti, S; Rugo, H; Muggia, F; O'Connor, B; Myerson, R; Stauffer, P; Hsu, I-C; Diederich, C; Straube, W; Boss, M-K; Boico, A; Craciunescu, O; Maccarini, P; Needham, D; Borys, N; Blackwell, KL; Dewhirst, MW
Published Date
- August 2014
Published In
Volume / Issue
- 30 / 5
Start / End Page
- 285 - 294
PubMed ID
- 25144817
Pubmed Central ID
- PMC4162656
Electronic International Standard Serial Number (EISSN)
- 1464-5157
Digital Object Identifier (DOI)
- 10.3109/02656736.2014.936049
Language
- eng
Conference Location
- England