Trastuzumab plus weekly epirubicin and paclitaxel for locally advanced and metastatic breast cancer: preliminary results of a feasibility-phase II study aimed at cardiotoxicity.
A feasibility-phase II study was conducted to assess the cardiotoxicity of weekly trastuzumab, epirubicin, and paclitaxel in patients with human epidermal growth factor receptor-2-positive metastatic breast cancer. Untreated patients with human epidermal growth factor receptor-2-positive advanced breast cancer received trastuzumab (day 1), and epirubicin (25 mg/m2) and paclitaxel (80 mg/m2) (day 2) on a weekly basis. The rate of patients with left-ventricular ejection fraction (L-VEF) reduction greater than 10% after 12 weeks was the primary end point. According to a two-stage model, an initial step with 15 patients was required; after 11 patients without toxicity, a second step with 21 patients was planned. After 255 courses in 15 patients (median treatment weeks: 18), the relative dose intensity was 94.7%. At 12 weeks, three patients (20%) displayed a L-VEF reduction greater than 10%, six and six (40%) patients showed a L-VEF reduction < or =10% or no change, respectively. Baseline, -12 weeks, and -24 weeks median L-VEF was 69% (range 61-77), 65% (range 60-76), and 65% (range 55-73), respectively. No EKG/cardiac signs were present. Thirteen patients had grade 3 alopecia and two patients had grade 3 asthenia, in the absence of severe hematological toxicity. Objective responses were observed in 11 patients (73.3%, 95% confidence interval 51.0-95.7), with 10 partial. The weekly administration of trastuzumab-epirubicin-paclitaxel is extremely tolerable, also with regard to L-VEF reduction. These results allowed entrance to the second step of the study.
Nisticò
Cecilia
C
Department of Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, Rome, Italy.
Bria
Emilio
E
Vaccaro
Vanja
V
Cuppone
Federica
F
Fornier
Monica
M
Sperduti
Isabella
I
Carpino
Armando
A
Izzo
Fiorentino
F
Tropea
Francesco
F
Cognetti
Francesco
F
Terzoli
Edmondo
E
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D000068878:Trastuzumab; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015251:Epirubicin; D000068878:Trastuzumab; D017239:Paclitaxel