Publications [#210132] of Mark W. Dewhirst

Papers Published

1. Z Vujaskovic, DW Kim, E Jones, L Lan, L McCall, MW Dewhirst, O Craciunescu, P Stauffer, V Liotcheva, A Betof, K Blackwell, A phase I/II study of neoadjuvant liposomal doxorubicin, paclitaxel, and hyperthermia in locally advanced breast cancer., International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, vol. 26 no. 5 (2010), pp. 514-21, ISSN 1464-5157 [doi]
   (last updated on 2012/10/26)

   Abstract:
   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.

   Keywords:
   Adult • Aged • Breast Neoplasms • Combined Modality Therapy • Doxorubicin • Female • Humans • Hyperthermia, Induced • Middle Aged • Neoadjuvant Therapy • Paclitaxel • Recurrence • Survival Analysis • Treatment Outcome • administration & dosage* • drug therapy • methods* • pathology • therapeutic use • therapy*