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1.
Cancer ; 118(19): 4694-705, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22434360

RESUMO

BACKGROUND: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors. This trial examined the efficacy of pemetrexed-cisplatin for SCCHN. METHODS: In a double-blind phase 3 trial, patients with recurrent or metastatic SCCHN and no prior systemic therapy for metastatic disease were randomized to pemetrexed (500 mg/m(2) ) plus cisplatin (75 mg/m(2) ; n = 398) or placebo plus cisplatin (75 mg/m(2) ; n = 397) to assess overall survival (OS) and secondary endpoints. RESULTS: Median OS was 7.3 months in the pemetrexed-cisplatin arm and 6.3 months in the placebo-cisplatin arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.75-1.02; P = .082). Median progression-free survival (PFS, months) was similar in both treatment arms (pemetrexed-cisplatin, 3.6; placebo-cisplatin, 2.8; HR, 0.88; 95% CI, 0.76-1.03; P = .166). Among patients with performance status 0 or 1, pemetrexed-cisplatin (n = 347) led to longer OS and PFS than placebo-cisplatin (n = 343; 8.4 vs 6.7 months; HR, 0.83; P = .026; 4.0 vs 3.0 months; HR, 0.84; P = .044, respectively). Among patients with oropharyngeal cancers, pemetrexed-cisplatin (n = 86) resulted in longer OS and PFS than placebo-cisplatin (n = 106; 9.9 vs 6.1 months; HR, 0.59; P = .002; 4.0 vs 3.4 months; HR, 0.73; P = .047, respectively). Pemetrexed-cisplatin toxicity was consistent with studies in other tumors. CONCLUSIONS: Pemetrexed-cisplatin compared with placebo-cisplatin did not significantly improve survival for the intent-to-treat population. However, in a prespecified subgroup analysis, pemetrexed-cisplatin showed OS and PFS advantage for patients with performance status 0 or 1 or oropharyngeal cancers.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Cisplatino/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Método Duplo-Cego , Feminino , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Pemetrexede , Resultado do Tratamento
2.
Cancer Med ; 9(17): 6234-6243, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32687266

RESUMO

Eflapegrastim (Rolontis® ) is a novel, long-acting hematopoietic growth factor consisting of a recombinant human granulocyte-colony stimulating factor (rhG-CSF) analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. We report results from a second pivotal, randomized, open-label, Phase 3 study comparing the efficacy and safety of eflapegrastim to pegfilgrastim for reducing the risk of chemotherapy-induced neutropenia. Patients with Stage I to IIIA early-stage breast cancer (ESBC) were randomized 1:1 to fixed-dose eflapegrastim 13.2 mg (3.6 mg G-CSF) or pegfilgrastim (6 mg G-CSF) administered one day after standard docetaxel/cyclophosphamide (TC) therapy for four cycles. The primary objective was to demonstrate noninferiority (NI) of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN; Grade 4) in Cycle 1. A total of 237 eligible patients were randomized 1:1 to receive either eflapegrastim (n = 118) or pegfilgrastim (n = 119). Cycle 1 severe neutropenia was observed in 20.3% (n = 24) of patients receiving eflapegrastim and 23.5% (n = 28) receiving pegfilgrastim. The DSN of eflapegrastim in Cycle 1 was noninferior to pegfilgrastim with a mean difference of -0.074 days (NI P-value < .0001). Noninferiority was maintained throughout the four treatment cycles (P < .0001 in all cycles). Other efficacy endpoints results were comparable between treatment arms, and adverse events, irrespective of causality and grade, were comparable between treatment arms. The results demonstrate noninferior efficacy and comparable safety for eflapegrastim, at a lower G-CSF dose, vs pegfilgrastim. The potential for the increased potency of eflapegrastim to deliver improved clinical benefit warrants further clinical study.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neutropenia Febril/tratamento farmacológico , Filgrastim/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Fármacos Hematológicos/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Neutropenia/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Neutropenia Febril/induzido quimicamente , Feminino , Filgrastim/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fármacos Hematológicos/efeitos adversos , Humanos , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Polietilenoglicóis/efeitos adversos
3.
Cancer Med ; 7(5): 1660-1669, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29573207

RESUMO

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.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Docetaxel/administração & dosagem , Filgrastim/análogos & derivados , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/efeitos adversos , Docetaxel/efeitos adversos , Esquema de Medicação , Feminino , Filgrastim/administração & dosagem , Filgrastim/efeitos adversos , Humanos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Polietilenoglicóis/efeitos adversos
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