RESUMO
PURPOSE: Trilaciclib is an intravenous cyclin-dependent kinase 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression (CIM) by protecting hematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myeloprotection). Here, we investigated the myeloprotective effects of trilaciclib among patients at increased risk of CIM. PATIENTS AND METHODS: Data were pooled from three randomized, double-blind, placebo-controlled, phase 2 clinical studies of trilaciclib administered prior to chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Myeloprotective outcomes were evaluated in patient subgroups based on age (<65 or ≥65 years), risk of chemotherapy-induced febrile neutropenia (FN), and risk of anemia or red blood cell (RBC) transfusions. For the FN and anemia analyses, risk factors were identified from published literature and used to classify patients into FN and anemia risk categories. Subgroup analysis based on age was also performed on patient reported outcome (PRO) measures. RESULTS: In total, 123 patients received trilaciclib and 119 patients received placebo. Myeloprotective benefits of trilaciclib were observed regardless of age, with greater effects observed among patients aged ≥65 years. Across FN risk factors and categories, trilaciclib had beneficial effects on neutrophil-related endpoints vs placebo, with greater effects observed in patients at higher risk of FN. Effects on RBC-related endpoints favored trilaciclib vs placebo, regardless of anemia risk factors and categories. Improvements in PROs with trilaciclib were observed irrespective of age group, but with greater improvements and less deterioration from baseline observed in older patients. CONCLUSION: By both decreasing the incidence of CIM and improving quality of life, trilaciclib has the potential to allow patients receiving chemotherapy for ES-SCLC, including patients who are older or more vulnerable to CIM, to receive chemotherapy on schedule and at standard-of-care doses, and to improve the experience for patients receiving chemotherapy to treat ES-SCLC. CLINICAL TRIAL NUMBERS: NCT02499770; NCT03041311; NCT02514447.
RESUMO
PURPOSE: A randomized phase II trial of two novel treatment strategies in the first-line management of advanced non-small-cell lung cancer patients with performance status (PS) 2. PATIENTS AND METHODS: Patients were assigned to docetaxel 30 mg/m(2) on days 1, 8, and 15 every 28 days in combination with either cetuximab 400 mg/m(2) loading dose followed by 250 mg/m(2) weekly (D + C) or bortezomib 1.6 mg/m(2) on days 1, 8, and 15 every 28 days (D + B) for up to 4 cycles. Patients with responding or stable disease continued cetuximab or bortezomib until progression. The primary end point was progression-free survival (PFS) rate at 6 months. RESULTS: Sixty-four patients were enrolled and 59 were included in this analysis. Complete or partial response rates were 13.3% and 10.3% for D + C and D + B, respectively. Median PFS was 3.4 months in the D + C arm and 1.9 months in the D + B arm. Corresponding figures for 6-month PFS were 27.8% and 13.8% and 5.0 and 3.9 months for median survival, respectively. Grade 3/4 hematologic toxicity was 16% for D + C and 21% for D + B, whereas nonhematologic toxicities were observed in 63% and 44% of patients, respectively. There was one treatment-related death in each arm. CONCLUSION: These results confirm the poor prognosis associated with a PS of 2 and the difficulty in translating recent advances in targeted therapy to this subset of patients. While the results in the D + C arm are numerically superior, neither combination met the prespecified PFS end point to justify further research in this setting.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Ácidos Borônicos/administração & dosagem , Bortezomib , Carcinoma Pulmonar de Células não Pequenas/patologia , Cetuximab , Docetaxel , Feminino , Nível de Saúde , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pirazinas/administração & dosagem , Taxoides/administração & dosagemRESUMO
We report the case of a 72-year-old woman with primary CNS lymphoma of the mid-brain and pons who had a complete response to oral temozolomide chemotherapy. She initially presented in early 2001 with several weeks of progressive memory loss and unresponsiveness. Because of her age and impaired renal function, she was a poor candidate for whole-brain radiotherapy or systemic high-dose methotrexate. After treatment with two cycles of temozolomide, restaging MRI revealed no evidence of disease. Her mental status improved significantly over this time. Temozolomide may represent a promising new drug for the treatment of primary CNS lymphoma.