Table 2.
Neoadjuvant metronomic chemotherapy in triple negative breast cancer
| Ref. | Type of study | n | Patient characteristic | Regimens | pCR | Adverse events | |
| Only MC | Hildebrand et al[34] | Single arm phase II | 18 | TNBC, ≥ T2 | Part 1 (12 wk) | 47.60% | Neutropenia G3-G4: 62% |
| 2016 | T4: 5 patients | Weekly DX 24 mg/m2 IV | Febrile neutropenia: 24% | ||||
| Node +: 12 patients | Daily CTX 60 mg/m2 PO | ||||||
| EC II: 47.4% | Followed by Part 2 (12 wk) | ||||||
| EC III: 28.6% | Weekly PTX 80 mg/m2 IV | ||||||
| Weekly C 2AUC IV | |||||||
| Tiley et al[35] | Single arm phase II | 17 | TNBC, T2-T4, N0-N1 | Part 1 (12 wk) | 46.60% | Thrombocytopenia G3: 5% | |
| 2012 | Median age: 45 yr (25-83) Inflammatory breast cancer: 3 | Weekly DX 24 mg/m2 IV | Neutropenia G4: 29% | ||||
| Daily CTX 60 mg/m2 PO | Neuropathy G3: 5% | ||||||
| Followed by Part 2 (12 wk) | |||||||
| Weekly PTX 80 mg/m2 IV | |||||||
| Weekly C 2AUC IV | |||||||
| Ignatova et al[36] | Single arm phase II | 40 | TNBC cТ2-4, N2-3, M0 | Part 1 (9 wk) | 60% | Neutropenia G3-4: 22.2% | |
| 2016 | Median age: 50 yr (27-69) | Weekly PTX 60 mg/mm2 IV | Mucositis 8.3% | ||||
| Histologic grade 3: 33.3% | Weekly C 2AUC IV | Hand-foot syndrome G3: 5.6% | |||||
| Ki67 > 20%: 100% | Then followed by Part 2 (9 wk) | ||||||
| Weekly DX 25 mg/m2 IV | |||||||
| Daily CTX 50 mg bid PO | |||||||
| Daily X 500 mg tid PO | |||||||
| Hybrid | Masuda et al[37] | Single arm phase II | 40 | ER < 10%, T2-T4, N0-N1 | Part 1 ( 4 Cycles every 21 d) | 47.50% | Neutropenia G3-4: 35% |
| 2014 | Median age 52 yr (33-69) | Day 1, 7, 14 PTX 80 mg/m2 IV | Hand foot syndrome G3-4: 8% | ||||
| N1: 40% | Daily CTX 50 mg PO | ||||||
| ER < 10%: 17.5% | Daily X 1200 mg PO | ||||||
| EC I: 12.5% | Followed by Part 2 (4 Cycles every 21 d) | ||||||
| EC II: 77.5% | Day 1 5-FU 500 mg/m2 IV | ||||||
| EC IIIA: 10% | Day 1 E 100 mg/m2 IV | ||||||
| Day 1 CTX 500 mg/m2 IV | |||||||
| Cancello et al[38] | Single arm phase II | 34 | ER ≤ 10%, PR ≤ 10%, Her2-Median age: 45 yr (31-64) | Part 1 (4 cycles every 21 d) | 56% | Neutropenia G3-4: 38% | |
| 2015 | Premenopausal: 73% | Day 1 5-FU 200 mg/m2 per day continuous | Anemia G3-4: 3% | ||||
| EC II: 35% | Day 1, 2 E 25 mg/m2 IV | ||||||
| EC III: 67% | Day 1, P 60 mg/m2 IV | ||||||
| Histologic grade 3: 82% | Followed by Part 2 (three cycles every 28 d) | ||||||
| Day 1, 7, 14 PTX 90 mg/m2 | |||||||
| Daily CTX 50 mg/d |
EC: Clinical stage; ER: Estrogen receptor; DX: Doxorubicin; CTX: Cyclophosphamide; PTX: Paclitaxel; C: Carboplatin; X: Capecitabine; 5-FU: 5-fluoracil; E: Epirubicin; P: Cisplatin; pCR: Pathologic response; TNBC: Triple negative breast cancer; MC: Metronomic chemotherapy.