Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer
| Autor: | Jennifer K. Litton, Nuhad K. Ibrahim, V. Valero, James L. Murray, William Fraser Symmans, Aysegul A. Sahin, Funda Meric-Bernstam, Lajos Pusztai, Argun Akcakanat, Gabriel N. Hortobagyi, Huiqin Chen, Kimberly B. Koenig, Stacy Moulder-Thompson, D. J. Crawford, GB Mills, Mark J. Dryden, A. M. Gonzalez-Angulo, Marjorie C. Green, E. Tarco, S. Liu, Shana L. Palla, Julia A. Moore, Sharon H. Giordano, Abenaa M. Brewster, P. R. Flores, Kim Anh Do |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Oncology medicine.medical_specialty Paclitaxel medicine.medical_treatment Phases of clinical research Triple Negative Breast Neoplasms Breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Everolimus skin and connective tissue diseases Cyclophosphamide Triple-negative breast cancer Neoadjuvant therapy Aged Epirubicin Sirolimus Chemotherapy business.industry TOR Serine-Threonine Kinases Original Articles Hematology Middle Aged medicine.disease Neoadjuvant Therapy Surgery Female sense organs Fluorouracil business Signal Transduction medicine.drug |
| Zdroj: | Annals of Oncology. 25:1122-1127 |
| ISSN: | 0923-7534 |
| DOI: | 10.1093/annonc/mdu124 |
| Popis: | Background Everolimus synergistically enhances taxane-induced cytotoxicity in breast cancer cells in vitro and in vivo in addition to demonstrating a direct antiproliferative activity. We aim to determine pharmacodynamics changes and response of adding everolimus to standard neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). Patients and methods Phase II study in patients with primary TNBC randomized to T-FEC (paclitaxel 80 mg/m2 i.v. weekly for 12 weeks, followed by 5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 every 3 weeks for four cycles) versus TR-FEC (paclitaxel 80 mg/m2 i.v. and everolimus 30 mg PO weekly for 12 weeks, followed by FEC). Tumor samples were collected to assess molecular changes in the PI3K/AKT/mTOR pathway, at baseline, 48 h, 12 weeks, and at surgery by reverse phase protein arrays (RPPA). Clinical end points included 12-week clinical response rate (12-week RR), pathological complete response (pCR), and toxicity. Results Sixty-two patients were registered, and 50 were randomized, 27 received T-FEC, and 23 received TR-FEC. Median age was 48 (range 31–75). There was downregulation of the mTOR pathway at 48 h in the TR-FEC arm. Twelve-week RR by ultrasound were 29.6% versus 47.8%, (P = 0.075), and pCR were 25.9% versus 30.4% (P = 0.76) for T-FEC and TR-FEC, respectively. mTOR downregulation at 48 h did not correlate with 12-week RR in the TR-FEC group (P = 0.58). Main NCI grade 3/4 toxicities included anemia, neutropenia, rash/desquamation, and vomiting in both arms. There was one case of grade 3 pneumonitis in the TR-FEC arm. No grade 3/4 stomatitis occurred. Conclusion The addition of everolimus to paclitaxel was well tolerated. Everolimus downregulated mTOR signaling but downregulation of mTOR at 48 h did not correlate with 12-week RR in the TR-FEC group. Clinical trial number NCT00499603. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|