TY - JOUR
T1 - 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
AU - Zagar, Timothy M.
AU - Vujaskovic, Zeljko
AU - Formenti, Silvia
AU - Rugo, Hope
AU - Muggia, Franco
AU - O'Connor, Brigid
AU - Myerson, Robert
AU - Stauffer, Paul
AU - Hsu, I. Chow
AU - Diederich, Chris
AU - Straube, William
AU - Boss, Mary Keara
AU - Boico, Alina
AU - Craciunescu, Oana
AU - Maccarini, Paolo
AU - Needham, David
AU - Borys, Nicholas
AU - Blackwell, Kimberly L.
AU - Dewhirst, Mark W.
N1 - Funding Information:
Mark Dewhirst owns stock in Celsion, and David Needham is the inventor of ThermoDox®. Trial A was funded by US National Institutes of Health grant P01 NIH NCI CA42745 and Celsion. Trial B was funded by Celsion, who also supplied the LTLD (ThermoDox®). Clinical trials registration numbers are NCT00346229, NCT00826085. The authors alone are responsible for the content and writing of the paper.
PY - 2014/8
Y1 - 2014/8
N2 - 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 40mg/m2; in the second trial, 11 subjects received LTLD at 40 or 50mg/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 256mg/m 2 of prior anthracyclines and a median dose of 61Gy of prior radiation. The median number of study treatments that subjects completed was four. The maximum tolerated dose was 50mg/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 50mg/m 2 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.
AB - 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 40mg/m2; in the second trial, 11 subjects received LTLD at 40 or 50mg/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 256mg/m 2 of prior anthracyclines and a median dose of 61Gy of prior radiation. The median number of study treatments that subjects completed was four. The maximum tolerated dose was 50mg/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 50mg/m 2 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.
KW - Hyperthermia
KW - Low temperature liposomal doxorubicin
KW - Recurrent breast cancer
UR - http://www.scopus.com/inward/record.url?scp=84906667095&partnerID=8YFLogxK
U2 - 10.3109/02656736.2014.936049
DO - 10.3109/02656736.2014.936049
M3 - Article
C2 - 25144817
AN - SCOPUS:84906667095
SN - 0265-6736
VL - 30
SP - 285
EP - 294
JO - International Journal of Hyperthermia
JF - International Journal of Hyperthermia
IS - 5
ER -