RESUMEN
This randomized, open-label, active-controlled study investigated the safety and efficacy of three doses of Rolontis (eflapegrastim), a novel, long-acting myeloid growth factor, versus pegfilgrastim in breast cancer patients being treated with docetaxel and cyclophosphamide (TC). The primary efficacy endpoint was duration of severe neutropenia (DSN) during the first cycle of treatment. Patients who were candidates for adjuvant/neoadjuvant TC chemotherapy were eligible for participation. TC was administered on Day 1, followed by 45, 135, or 270 µg/kg Rolontis or 6 mg pegfilgrastim on Day 2. Complete blood counts were monitored daily when the absolute neutrophil count (ANC) fell to <1.5 × 109 /L. Up to four cycles of TC were investigated. The difference in DSN (time from ANC <0.5 × 109 /L to ANC recovery ≥2.0 × 109 /L) between the Rolontis and pegfilgrastim groups was -0.28 days (confidence interval [CI]: -0.56, -0.06) at 270 µg/kg, 0.14 days (CI: -0.28, 0.64) at 135 µg/kg, and 0.72 days (CI: 0.19, 1.27) at 45 µg/kg. Noninferiority to pegfilgrastim was demonstrated at 135 µg/kg (P = 0.002) and 270 µg/kg (P < .001), with superiority demonstrated at 270 µg/kg (0.03 days; P = 0.023). The most common treatment-related adverse events (AEs) were bone pain, myalgia, arthralgia, back pain, and elevated white blood cell counts, with similar incidences across groups. All doses of Rolontis were well tolerated, and no new or significant treatment-related toxicities were observed. In Cycle 1, Rolontis demonstrated noninferiority at the 135 µg/kg dose and statistical superiority in DSN at the 270 µg/kg dose when compared to pegfilgrastim.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Docetaxel/administración & dosificación , Filgrastim/análogos & derivados , Polietilenglicoles/administración & dosificación , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/efectos adversos , Docetaxel/efectos adversos , Esquema de Medicación , Femenino , Filgrastim/administración & dosificación , Filgrastim/efectos adversos , Humanos , Persona de Mediana Edad , Neutropenia/inducido químicamente , Neutropenia/epidemiología , Polietilenglicoles/efectos adversosRESUMEN
BACKGROUND: The knowledge of the epidemiology of left ventricular systolic dysfunction (LVSD) in relationship with cardiovascular diseases, their risk factors and history of previous anticancer therapy may lead to development of safer and more effective therapeutic strategies in patients with breast cancer (BC). PATIENTS AND METHODS: Oncologists from various Polish Centers reported 299 new cases of metastatic BC requiring chemotherapy. All registered previous cardiological and oncological therapies should be conducted in accordance with the mandatory guidelines. RESULTS: Twelve new cases (4%) of LVSD were recognized in echocardiography before current chemotherapy. Multivariate logistic regression analysis revealed a significant association of LVSD with hypercholesterolemia (odds ratio (OR)=8.83; 95% confidence interval (CI)=1.44-54.16; p<0.02), prior myocardial infarction (OR=26.81; 95%CI=2.26-318.43; p<0.01), prior antracycline-based therapy either neoadjuvant (OR=13.21; 95%CI=2.18-80.12, p=0.005) or adjuvant (OR=6.94; 95%CI=1.003-47.985, p<0.05). CONCLUSION: LVSD in metastatic BC reflects common negative effects of hypercholesterolemia, coronary events and neoadjuvant/adjuvant chemotherapy with anthracyclines.