RESUMEN
BACKGROUND: This study compared efficacy and safety of TA4415V, a trastuzumab biosimilar, with reference trastuzumab in patients with human epidermal growth factor receptor 2-positive (HER2-positive) early-stage breast cancer treated in the neoadjuvant setting in Iran. METHODS: Patients were randomly assigned to receive neoadjuvant TA4415V or reference trastuzumab concurrently with docetaxel (TH phase) for 4 cycles after treatment with 4 cycles of doxorubicin and cyclophosphamide (AC phase). Chemotherapy was followed by surgery. The primary endpoint was the comparison of pathologic complete response (pCR) rate in the per-protocol population. Secondary endpoints included comparisons of overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Ninety-two participants were analyzed in the per-protocol population (TA4415V, n = 48; reference trastuzumab, n = 44). The pCR rates were 37.50% and 34.09% with TA4415V and reference drug, respectively. The 95% CI of the estimated treatment outcome difference (- 0·03 [95% CI - 0.23 to 0.16]) was within the non-inferiority margin. No statistically significant difference was observed between the groups for other efficacy variables in the ITT population: ORR (89.13% vs. 83.33%; p = 0.72) and BCS (20.37% vs. 12.96%; p = 0.42) in the TA4415V and reference drug group, respectively. At least one grade 3 or 4 adverse events occurred in 27 (50%) patients in the TA4415V group versus 29 (53.70%) in the reference trastuzumab group (p = 0.70). The decrease in left ventricular ejection fraction (LVEF), as an adverse event of special interest (AESI) for trastuzumab, was compared between treatment groups in TH phase. Results demonstrated an LVEF decrease in 7 (12.96%) and 9 (16.67%) patients in TA4415V and reference trastuzumab groups, respectively (p = 0.59). Anti-drug antibodies (ADA) were not detected in any samples of groups. CONCLUSIONS: Non-inferiority for efficacy was demonstrated between TA4415V and Herceptin based on the ratio of pCR rates in HER2-positive early breast cancer patients. In addition, ORR and BCS, as secondary endpoints, were not significantly different. Safety profile and immunogenicity were also comparable between the two groups.
Asunto(s)
Biosimilares Farmacéuticos , Neoplasias de la Mama , Trastuzumab , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biosimilares Farmacéuticos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Humanos , Receptor ErbB-2/análisis , Receptor ErbB-2/uso terapéutico , Volumen Sistólico , Trastuzumab/efectos adversos , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
PURPOSE: Phase IV clinical trials are required to evaluate the real-world safety and effectiveness of drugs. This study aimed to evaluate the safety and effectiveness of once-per-cycle administration of PegaGen® (pegfilgrastim, CinnaGen, Iran) in cancer patients. METHODS: In this open-label, multicenter, prospective, real-world, post-marketing surveillance study, patients with any type of cancer receiving chemotherapy regimens with a high risk of febrile neutropenia (FN) were included if they were prescribed pegfilgrastim for FN prophylaxis. The primary objective of this study was to assess the safety and the secondary objective was to assess the effectiveness of pegfilgrastim in the prevention of FN in cancer patients. RESULTS: A total of 654 patients (51.73 ± 15.12 years of age) were enrolled and 3615 cycles of pegfilgrastim injections were recorded. The most common malignancies among the study patients were breast cancer (n = 192, 29.36%), lymphoma (n = 131, 20.03%), and gastric cancer (n = 65, 9.94%). The median (Q1, Q3) number of pegfilgrastim cycles per patient was 6 (4, 7). A single 6 mg dose was injected in 99.17% of the cycles. A total number of 816 adverse events (AEs) were reported in 246 patients (37.62%). Bone pain was recorded in 141 patients (21.56%) and in 440 cycles (12.17%). Among all patients, 45 patients (6.88%) experienced FN 51 times, and FN frequency was 1.4% among cycles. Moreover, 14 (2.14%) patients were hospitalized following FN. Antibiotics were administered to 24 patients (3.67%) for FN treatment. CONCLUSION: The results from this post-marketing surveillance study support the safety and effectiveness of PegaGen® used for the prevention of chemotherapy-induced FN in patients with various types of cancer and treatment regimens. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04460079.
Asunto(s)
Antineoplásicos , Neoplasias de la Mama , Neutropenia Febril Inducida por Quimioterapia , Neutropenia Febril , Antibacterianos/uso terapéutico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Neutropenia Febril Inducida por Quimioterapia/etiología , Neutropenia Febril Inducida por Quimioterapia/prevención & control , Neutropenia Febril/inducido químicamente , Neutropenia Febril/tratamiento farmacológico , Neutropenia Febril/prevención & control , Femenino , Filgrastim/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Polietilenglicoles/efectos adversos , Vigilancia de Productos Comercializados , Estudios Prospectivos , Proteínas Recombinantes/uso terapéuticoRESUMEN
BACKGROUND: Currently, the main goal of cancer research is to increase longevity of patients suffering malignant cancers. The promising results of BCc1 in vitro and vivo experiments made us look into the effect of BCc1 nanomedicine on patients with cancer in a clinical trial. METHODS: The present investigation was a randomized, double-blind, placebo-controlled, parallel, and multicenter study in which 123 patients (30-to-85-year-old men and women) with metastatic and non-metastatic gastric cancer, in two separate groups of BCc1 nanomedicine or placebo, were selected using a permuted block randomization method. For metastatic and non-metastatic patients, a daily dose of 3000 and 1500 mg was prescribed, respectively. Overall survival (OS) as the primary endpoint and quality of life (measured using QLQ-STO22) and adverse effects as the secondary endpoints were studied. RESULTS: In metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (174 days [95% confidence interval (CI) 82.37-265.62]) than in placebo (62 days [95% CI 0-153.42]); hazard ratio (HR): 0.5 [95% CI 0.25-0.98; p = 0.046]. In non-metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (529 days [95% CI 393.245-664.75]) than in placebo (345 days [95% CI 134.85-555.14]); HR: 0.324 [95% CI 0.97-1.07; p = 0.066]. The QLQ-STO22 assessment showed a mean difference improvement of 3.25 and 2.29 (p value > 0.05) in BCc1 nanomedicine and a mean difference deterioration of - 4.42 and - 3 (p-value < 0.05) in placebo with metastatic and non-metastatic patients, respectively. No adverse effects were observed. CONCLUSION: The findings of this trial has provided evidence for the potential capacity of BCc1 nanomedicine for treatment of cancer. Trial registration IRCTID, IRCT2017101935423N1. Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1.
Asunto(s)
Adenocarcinoma/terapia , Nanocompuestos/química , Neoplasias Gástricas/terapia , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nanomedicina/métodos , Metástasis de la Neoplasia , Manejo del Dolor , Modelos de Riesgos Proporcionales , Calidad de Vida , Neoplasias Gástricas/patología , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of the study was to assess the efficacy and safety of epoetin beta once-weekly in anemic patients with solid tumors treated with chemotherapy. METHOD: Prospective, open-label, multicenter, single-arm study of epoetin beta 30 000 I.U. once-weekly in anemic patients with solid tumors receiving chemotherapy (n = 365). RESULTS: Epoetin beta increased mean haemoglobin (Hb) levels from 10.3 +/- 0.9 g/dL at baseline to 12.3+/-2.0 g/dL at week 12. The response rate was achieved in 61% (CI 95%: 55-68) of the patients. The mean Hb level increased was 1.8 g/dL (CI 95%: 1.5-2,0); in lung cancer patients (n = 102) Hb increase was 2.7 g/dL. Treatment with epoetin beta was well tolerated; only 1.4 % patients had thrombotic events. CONCLUSION: Epoetin beta (30 000 I.U. once weekly) increased Hb levels and was well-tolerated to correct anemia in patients with solid tumors treated with chemotherapy.
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Anemia/inducido químicamente , Anemia/tratamiento farmacológico , Antineoplásicos/efectos adversos , Eritropoyetina/uso terapéutico , Neoplasias/complicaciones , Anciano , Eritropoyetina/efectos adversos , Femenino , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas RecombinantesRESUMEN
OBJECTIVES: This study aimed to provide further clinical evidence for the efficacy and safety of epoetin beta once weekly across a wide range of cancer types. METHODS: This was a multicenter, open-label, prospective, single-arm study in patients with either a solid tumor or non-myeloid hematological malignancy, receiving or scheduled to receive further chemotherapy. Patients received epoetin beta 30,000 IU subcutaneously once weekly for 16 weeks. The primary efficacy endpoint was the change in hemoglobin (Hb) level according to the patient's baseline Hb level. RESULTS: A total of 691 patients were included in the intent-to-treat population. Epoetin beta effectively increased Hb levels (a mean increase from baseline of 1.1 g/dl by week 4 and 2.2 g/dl by week 12). Hb response was achieved in 60.4% of all patients and 61.2% of those with baseline Hb <11 g/dl. Hb response was similar in patients with solid tumors (60.5%) and non-myeloid hematological malignancies (60.2%). Type of chemotherapy and baseline platelet count were independent predictive factors for response. Epoetin beta treatment was well tolerated. CONCLUSIONS: Epoetin beta 30,000 IU once weekly effectively increases Hb levels, is well tolerated and has similar efficacy in anemic patients with solid tumors or non-myeloid hematological malignancies.
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Anemia/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Hematínicos/uso terapéutico , Neoplasias Hematológicas , Neoplasias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia/etiología , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Estudios Prospectivos , Proteínas RecombinantesAsunto(s)
Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Linfohistiocitosis Hemofagocítica/complicaciones , Linfoma de Células B/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Enfermedades de la Piel/etiología , Infecciones por Virus de Epstein-Barr/patología , Infecciones por Virus de Epstein-Barr/virología , Humanos , Linfohistiocitosis Hemofagocítica/patología , Linfohistiocitosis Hemofagocítica/virología , Linfoma de Células B/patología , Linfoma de Células B/virología , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/virología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Enfermedades de la Piel/patología , Enfermedades de la Piel/terapiaRESUMEN
OBJECTIVE: Occupational causes of haematological malignancies are relatively uncommon, under-studied and under-identified. They are also often unrecognized by clinicians. This review summarizes the principal epidemiologic studies on this topic. METHODS: We analyzed the recent relevant human data found in the Medline, the Pascal and the BDSP databases. RESULTS: Benzene and ionizing radiation are the only agents conclusively demonstrated to be carcinogenic to the haematopoietic system. In particular, both exposures are strongly associated with acute myeloid leukaemia. Low doses of both may also be related to myeloid malignancies. Infectious agents and pesticides are also thought to induce lymphoproliferative cancers. Some studies show an association between haematological malignancies and low-frequency electromagnetic fields and organic solvents. All of these suspected occupational causes must be confirmed by further studies. CONCLUSIONS: Better knowledge and understanding of occupational causes of haematological malignancies are necessary to improve their prevention and compensation.
Asunto(s)
Sustancias Peligrosas/toxicidad , Neoplasias Hematológicas/epidemiología , Enfermedades Profesionales/epidemiología , Radiación Ionizante , Causalidad , Industria Química , Relación Dosis-Respuesta en la Radiación , Campos Electromagnéticos , Monitoreo del Ambiente/estadística & datos numéricos , Monitoreo Epidemiológico , Neoplasias Hematológicas/inducido químicamente , Humanos , Leucemia/epidemiología , Trastornos Linfoproliferativos/epidemiología , Síndromes Mielodisplásicos/epidemiología , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/análisis , Exposición Profesional/estadística & datos numéricos , Ocupaciones/clasificación , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Doxorubicin-based immunochemotherapy, with interferon, has been shown to improve survival in patients with advanced follicular lymphoma. High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy. In a randomized study using a purged autologous stem-cell support, we compared these 2 approaches in patients with advanced follicular lymphoma. Newly diagnosed advanced follicular lymphoma patients (172 patients) were randomly assigned either to an immunochemotherapy regimen (cyclophosphamide, doxorubicin, teniposide, prednisone, and interferon) or to a high-dose therapy followed by purged autologous stem-cell transplantation. Compared with the patients who received chemotherapy and interferon, patients treated with high-dose therapy had a higher response rate (69% vs 81%, P = .045) and a longer median event-free survival (not reached vs 45 months). This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation. The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy. Autologous stem-cell transplantation cannot be considered as the standard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden.
Asunto(s)
Doxorrubicina/uso terapéutico , Linfoma Folicular/patología , Linfoma Folicular/terapia , Trasplante de Células Madre , Adulto , Progresión de la Enfermedad , Doxorrubicina/efectos adversos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Francia , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/cirugía , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Recurrencia , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
Lymphocyte-predominant Hodgkin lymphoma (LPHL), according to the Revised European-American Lymphoma classification, was considered on a retrospective basis as a specific clinical entity with a large majority of patients at clinical stage (CS) IA or IIA. Of the 500 patients with CS IA/IIA Hodgkin lymphoma (HL) prospectively treated between 1981 and 1996 by one or 3 courses of anthracycline-based chemotherapies combined with high-dose extended irradiation, disease in 42 patients was reclassified as LPHL. These 42 patients, none of whom had mediastinal involvement (MI), were compared with the 458 patients with classical HL (cHL), 144 without MI and 314 with MI. Surprisingly, the male-female ratio, age, first site involved, hemoglobin level, lymphocyte count, and sedimentation rate of patients with LPHL and cHL without MI were identical and significantly different from those of patients with cHL with MI. Moreover, 15-year HL mortality rates were similarly low in patients with LPHL (2.4%) and cHL without MI (0.7%). Overall survival rates were also similar (86% and 82%) and as high as 100% and 95% in patients treated before the age of 40 years. This study demonstrated that LPHL and cHL without MI shared the same presenting characteristics and the same excellent long-term prognosis after a brief anthracycline-based chemotherapy plus high-dose extended irradiation.