A phase I/II study of neoadjuvant liposomal doxorubicin, paclitaxel, and hyperthermia in locally advanced breast cancer.
OBJECTIVE
The prognosis for locally advanced breast cancer (LABC) patients continues to be poor, with an estimated five-year survival of only 50-60%. Preclinical data demonstrates enhanced therapeutic efficacy with liposomal encapsulation of doxorubicin combined with hyperthermia (HT). Therefore this phase I/II study was designed to evaluate the safety and efficacy of a novel neoadjuvant combination treatment of paclitaxel, liposomal doxorubicin, and hyperthermia.


METHODS
Eligible patients received four cycles of neoadjuvant liposomal doxorubicin (30-75 mg/m(2)), paclitaxel (100-175 mg/m(2)), and hyperthermia. They subsequently underwent either a modified radical mastectomy or lumpectomy with axillary node dissection followed by radiation therapy and then eight cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy.


RESULTS
Forty-seven patients with stage IIB-III LABC were enrolled and 43 patients were evaluable. Fourteen patients (33%) had inflammatory breast cancer. Combined (partial + complete) clinical response rate was 72% and combined pathological response rate was 60%. Four patients achieved a pathologically complete response. Sixteen patients were eligible for breast-conserving surgery. The cumulative equivalent minutes (CEM 43) at T90 (tenth percentile of temperature distribution) was significantly greater for those with a pathological response. Four-year disease-free survival was 63% (95% CI, 46%-76%) and the four-year overall survival was 75% (95% CI, 58-86%).


CONCLUSIONS
Neoadjuvant therapy using paclitaxel, liposomal doxorubicin and hyperthermia is a feasible and well tolerated treatment strategy in patients with LABC. The thermal dose parameter CEM 43 T90 was significantly correlated with attaining a pathological response.
Vujaskovic
Zeljko
Z
Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA. vujas@radonc.duke.edu
Kim
Dong W
DW
Jones
Ellen
E
Lan
Lan
L
McCall
Linda
L
Dewhirst
Mark W
MW
Craciunescu
Oana
O
Stauffer
Paul
P
Liotcheva
Vlayka
V
Betof
Allison
A
Blackwell
Kimberly
K
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D012008:Recurrence; D016019:Survival Analysis; D016896:Treatment Outcome
D004317:Doxorubicin; D017239:Paclitaxel