RESUMEN
This retrospective analysis compared standard regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with the dose-dense ABVD regimen (ABVD-21) in terms of efficacy and toxicity. Patients who had early-stage unfavorable or advanced Hodgkin's lymphoma (HL) according to German Hodgkin Study Group criteria from March 1999 to February 2011 were analyzed for treatment response, long-term survival and hematological toxicity. There were 85 patients in the ABVD-21 group and 118 patients in the ABVD group respectively. The complete remission rates after completion of treatment were 92.9% and 90.7% for ABVD-21 and ABVD, respectively. During a median follow-up period of 62 months, no significant difference was found in projected 10-year progression-free survival (PFS) and overall survival (OS) rates (84.7% and 94.1% respectively for ABVD-21; 81.4% and 91.5% for ABVD). Subgroup analyses showed that ABVD-21 was significantly better than ABVD for patients with IPS≥3 in terms of PFS and OS rates. Grade 3 to 4 leukopenia (51.8% vs. 28.8%, P=0.001) and neutropenia (57.6% vs. 39.0%, P=0.009) were more common with ABVD-21. We were led to conclude that dose-dense ABVD did not result in better tumor control and overall survival than did ABVD for early-stage unfavorable HL. However, patients at high risk, for example, with IPS≥3, may benefit from dose-dense ABVD.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Terapia Combinada/métodos , Enfermedad de Hodgkin/tratamiento farmacológico , Adulto , Bleomicina/administración & dosificación , Dacarbazina/administración & dosificación , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Femenino , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona , Estudios Retrospectivos , Vinblastina/administración & dosificaciónRESUMEN
The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 µg/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 µg/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Neutropenia/inducido químicamente , Neutropenia/prevención & control , Polietilenglicoles/administración & dosificación , Adulto , Anciano , Estudios Cruzados , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversosRESUMEN
OBJECTIVE: To explore the association between different epidermal growth factor receptor (EGFR) mutation status and survival in pemetrexed-based chemotherapy for advanced non-small-cell lung cancer (NSCLC). METHODS: A retrospective cohort study was performed to assess 146 patients with advanced NSCLC at Cancer Institute/Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. The first-line regimens included pemetrexed based chemotherapy (pemetrexed first-line therapy group, n = 79), pemetrexed based chemotherapy plus pemetrexed maintenance chemotherapy (pemetrexed maintenance therapy group, n = 38) and pemetrexed based chemotherapy plus tyrosine kinase inhibitors (TKI) maintenance therapy (TKI maintenance therapy group, n = 29). Median progression-free survival (PFS) was determined.For comparison, median PFS was evaluated for EGFR-positive,EGFR-negative versus EGFR mutation unknown NSCLC patients in first-line pemetrexed therapy and pemetrexed maintenance therapy groups. RESULTS: The median PFS was 4.6 (95%CI: 2.8-6.4), 9.8 (95%CI: 6.1-13.5) and 14.5 (95%CI: 11.8-17.2) months in pemetrexed first-line therapy, pemetrexed maintenance therapy and TKI maintenance therapy groups respectively (P = 0.000). No difference existed in PFS for pemetrexed first-line therapy group with a median PFS of 5.2 (95%CI: 2.8-7.7), 4.0 (95%CI: 0-10.8) and 4.6 (95%CI: 3.4-5.8) months respectively (P = 0.661). Among EGFR-positive,EGFR-negative and EGFR mutation status unknown patients in pemetrexed maintenance therapy group, the median PFS was 8.5 (95%CI: 4.0-13.1), 12.6 (95%CI: 11.6-13.7) and 8.0 (95%CI: 5.8-10.3) months with no significant statistical difference (P = 0.468). CONCLUSIONS: No significant difference exists in survival between different EGFR mutation status for pemetrexed based first-line chemotherapy. And TKI maintenance therapy is associated with better survival than pemetrexed maintenance therapy regardless of EGFR status.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Glutamatos/administración & dosificación , Guanina/administración & dosificación , Guanina/análogos & derivados , Humanos , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mutación , Pemetrexed , Estudios RetrospectivosRESUMEN
OBJECTIVE: To observe the efficacy and safety of albumin-bound paclitaxel (ABP) monotherapy in treating recurrent advanced non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analyzed the short-term efficacy and toxicities of ABP monotherapy in treating 21 patients who had previously undergone multiple cycles of therapy for their advanced NSCLC in our hospital since 2010. The treatment-related survival was also analyzed. RESULTS: Of these 21 patients, the best overall response was partial response (PR) in 6 patients (28.6%), stable disease (SD) in 10 patients (47.6%), and progressive disease (PD) in 5 patients (23.8%). The overall response rate (ORR) was 28.6% and the disease control rate (DCR) (PR + SD) was 76.2%. The median progression-free survival (PFS) was 4.0 months (95% CI, 5.0-7.0 months). The main grade 3/4 toxicities included neutropenia (11.1%), peripheral nerve toxicity (5.6%), muscle and joint aches (5.6%), and fatigue (5.6%). CONCLUSIONS: The ABP monotherapy can achieve good objective response in advanced NSCLC patients who have previously received multiple cycles of treatment and be well tolerated.
RESUMEN
PURPOSE: ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study. METHODS: Adults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0-2 and asymptomatic, stable central nervous system (CNS) metastases were included. All patients received once-daily osimertinib 80 mg orally. The outcomes included investigator-assessed clinical response, progression-free survival (PFS), time-to-treatment discontinuation (TTD), and safety. RESULTS: A total of 1350 patients were included. Response rate was 55.7% (95% confidence interval [CI] 0.53-0.58). The median PFS and the median TTD were 11.7 months (95% CI 11.1-12.5) and 13.9 months (95% CI 13.1-15.2), respectively. Overall, 389 patients (28.8%) had at least one protocol-specified adverse event (AE); AEs of interstitial lung diseases/pneumonitis-like events and QT prolongation were reported in 3 (0.2%) and 59 (4.4%) patients, respectively. CONCLUSION: Osimertinib was effective in Chinese patients with T790M-positive NSCLC who had progressed after first- or second-generation EGFR-TKI in real-word setting and the results were consistent with ASTRIS study overall population and AURA studies. No new safety signals or events were identified. CLINICAL TRIAL NUMBER: NCT02474355.
Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Compuestos de Anilina/efectos adversos , Antineoplásicos/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Pueblos del Este de Asia , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
OBJECTIVE: To evaluate the efficacy of erlotinib in patients with metastasis of non-small cell lung cancer who had benefits from initial gefitinib treatment but finally demonstrated resistance, especially in those of unknown EGFR mutation status, and to compare the efficacy of erlotinib between patients who received erlotinib immediately after gefitinib failure and those who received chemotherapy before erlotinib. METHODS: Forty Chinese patients who had been treated with erlotinib (150 mg daily) after gefitinib (250 mg daily) failure were evaluated retrospectively. All of these patients had achieved gefitinib treatment for at least three months with response of partial remission or stable disease. Among them, 16 patients shifted to erlotinib immediately after progression (Group G-E), and the other 24 patients inserted chemotherapy between gefitinib and erlotinib (Group G-C-E). RESULTS: In the whole group, the disease control rate (DCR) of erlotinib was 52.5% (21/40) while the objective response rate (RR) was only 10.0% (4/40). The RR of the group G-E was 6.2% and the group G-C-E was 12.5%, and the DCR was 56.2% and 50.0% in the two groups, respectively, both without significant differences (P = 0.638 and P = 0.755). There was no correlation between the efficacy of erlotinib and that of initial gefitinib in both group G-E and group G-C-E (P = 0.365 and P = 0.658). The median progression-free survival (PFS) and overall survival (OS) for the erlotinib treatment were 3.0 and 12.0 months in the 40 patients. Statistically no significant difference was observed in PFS (4 months in the group G-E and 2 months in the group G-C-E, P = 0.768) and OS (12 months in both Groups, P = 0.510). CONCLUSIONS: Erlotinib can be considered either immediately after gefitinib failure or following the insertion of chemotherapy after gefitinib failure in progressive non-small cell lung cancer patients who initially benefited from gefitinib.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Mutación , Quinazolinas/uso terapéutico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Receptores ErbB/antagonistas & inhibidores , Clorhidrato de Erlotinib , Femenino , Estudios de Seguimiento , Gefitinib , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Inhibidores de Proteínas Quinasas/uso terapéutico , Inducción de Remisión , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: The aim of this study was to investigate the clinicopathological characteristics, effective treatment and prognosis in childhood and adolescent Hodgkin's lymphoma. METHODS: A total of 88 patients with childhood and adolescent Hodgkin's lymphoma were treated in the Cancer Hospital of CAMS from 1998 to 2005. The clinicopathological and follow-up data of the patients were retrospectively reviewed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. COX multivariate prognosis analysis was performed. RESULTS: The 2-year event-free survival rate of the 88 patients was 86.4%, the 5-year event-free survival rate was 61.4%, and the 5-year overall survival rate was 95.5%. Univariate analysis showed that the stage of disease (P = 0.033), "B" symptoms (P = 0.028), bulky disease (P = 0.007), splenomegaly (P = 0.050), LDH elevation (P = 0.020), chemotherapy regimen (P = 0.003) were prognostic factors in the 5-year event-free survival rate. Splenomegaly (P = 0.039), LDH elevation (P = 0.033), chemotherapy regimen (P = 0.008) were prognostic factors of 5-year overall survival rate. Multivariate analysis showed that chemotherapy regimen (P = 0.033), stage of disease (P = 0.023), LDH elevation (P = 0.008), "B" symptoms (P = 0.044), bulky disease (P = 0.009) were independent prognostic factors of 5-year event-free survival rate. The chemotherapy regimen (P = 0.012) and LDH elevation (P = 0.046) were independent prognostic factors of 5-year overall survival rate. CONCLUSIONS: The non-ABVD chemotherapy regimen, stage IV disease, LDH elevation, associated with "B" symptoms and bulky disease are independent prognostic factors of 5-year event-free survival rate. LDH elevation and non-ABVD chemotherapy regimen are independent prognostic factors of 5-year overall survival rate.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/patología , Adolescente , Bleomicina/uso terapéutico , Niño , Preescolar , Terapia Combinada , Ciclofosfamida/uso terapéutico , Dacarbazina/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/radioterapia , Humanos , L-Lactato Deshidrogenasa/sangre , Masculino , Mecloretamina/uso terapéutico , Estadificación de Neoplasias , Prednisona/uso terapéutico , Procarbazina/uso terapéutico , Estudios Retrospectivos , Esplenomegalia/etiología , Tasa de Supervivencia , Vinblastina/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
OBJECTIVE: To analyze the liver function in patients with diffuse large B-cell lymphoma(DLBCL), who are hepatitis B surface antigen negative/antibody to hepatitis B core antigen positive (HBsAg-/HBcAb+), treated with CHOP and R-CHOP regimens. METHODS: In this retrospective study, 86 DLBCL patients, who were HBsAg-/HBcAb+, were collected from Cancer Hospital of Chinese Academy of Medical Sciences between January 2005 and December 2008. The patients were given at least two cycles of chemotherapy using CHOP-like or R-CHOP-like regimen without anti-HBV treatment, and followed-up for at least 12 months after completion of therapy. RESULTS: Forty-seven patients received CHOP-like regimen while 39 patients received R-CHOP-like regimen. There were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group after the 1st, 2nd, 3rd, 4th and 6th cycles (22.7% - 46.7% with CHOP and 17.6% - 34.2% with R-CHOP, respectively, (all P > 0.05), except for the 5th cycles (28.6% vs. 6.2%, P = 0.026). Liver function in most patients in CHOP group and R-CHOP group was normal after every cycle (53.3% - 77.3% and 65.8%-93.8%, respectively). Meanwhile, there were no significant differences in the degree of liver dysfunction between CHOP group and R-CHOP group in the 1st-3rd month, 4th-6th month, 7th-9th month and 10th-12th month after completion of therapy (7.7% - 40.0% with CHOP and 7.4% - 32.0% with R-CHOP, respectively, all P > 0.05). CONCLUSIONS: The present study reveals a low incidence of liver dysfunction in HBsAg-/HBcAb+ DLBCL patients, both in CHOP group and in R-CHOP group. It may indicate a potential low incidence of HBV reactivation in these groups, and Rituximab do not increase the rate of liver dysfunction. Therefore, these data may not support regularly prophylactic antiviral therapy during chemotherapy, but close monitoring of liver function, HBV serum markers and HBV DNA level are demanded.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Alanina Transaminasa/sangre , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Anticuerpos contra la Hepatitis B/metabolismo , Antígenos del Núcleo de la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/metabolismo , Humanos , Pruebas de Función Hepática , Linfoma de Células B Grandes Difuso/sangre , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/virología , Masculino , Prednisolona/uso terapéutico , Prednisona/uso terapéutico , Estudios Retrospectivos , Rituximab , Vincristina/uso terapéuticoRESUMEN
OBJECTIVE: To evaluate the effect of recombinant human interleukin 11 (rhIL-11) on hematological recovery after autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoma. METHODS: A retrospective study was carried out on 73 patients with lymphoma after AHSCT. The patients were divided into two groups. The study group (n = 35) received rhIL-11 1.5 mg daily from the fifth day after AHSCT to the day when platelets recovering to 80.0×109/L. The control group (n = 38) did not receive rhIL-11 after AHSCT. RESULTS: All the 73 patients finished AHSCT from Mar 2003 to Dec 2008 in our department. Thirty-five patients received rhIL-11 and 38 patients did not. In the rhIL-11 group and control group, the nadir of platelet was (18.9 ± 5.0)×109/L and (21.5 ± 6.0)×109/L, respectively, with a significant difference (P = 0.04). The median time of platelet recovering to 50.0×109/L was (14.3 ± 5.5) d and (13.2 ± 4.5) d (P = 0.37) in the two groups. There was no significant difference (P = 0.82) in the median numbers of platelet transfusion in the two groups. The curves of the mean of daily absolute platelet counts of the two groups were similar (P = 0.22). Adverse events related to rhIL-11 were not found in the rhIL-11 group. CONCLUSION: The results of this study do not show obviously accelerating effect of rhIL-11 on the platelet recovery in lymphoma patients after AHSCT and obvious increase of adverse events after rhIL-11 administration.
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Trasplante de Células Madre Hematopoyéticas , Interleucina-11/administración & dosificación , Linfoma/terapia , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Recuento de Plaquetas , Transfusión de Plaquetas , Proteínas Recombinantes/administración & dosificación , Estudios Retrospectivos , Trasplante AutólogoRESUMEN
Anaplastic large-cell lymphoma (ALCL) is characterized by frequently presenting adverse factors at diagnosis. Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients. However, few compared these approaches with conventional chemotherapy to validate their superiority. Here, we report a study comparing the efficacy of peripheral blood stem cell transplantation (PBSCT) and conventional chemotherapy on ALCL. A total of 64 patients with primary systemic ALCL were studied retrospectively. The median follow-up period was 51 months (range, 1-167 months). For 48 patients undergoing conventional chemotherapy only, the 4-year event-free survival (EFS) and overall survival (OS) rates were 70.7% and 88.3%, respectively. Altogether, 16 patients underwent PBSCT, including 11 at first remission (CR1/PR1), 3 at second remission, and 2 with disease progression during first-line chemotherapy. The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%, respectively. Compared with conventional chemotherapy, PBSCT did not show superiority either in EFS (P = 0.240) or in OS (P = 0.580) when applied at first remission. Univariate analysis showed that patients with B symptoms (P = 0.001), stage III/IV disease (P = 0.008), bulky disease (P = 0.075), negative anaplastic lymphoma kinase (ALK) expression (P = 0.059), and age ≤ 60 years (P = 0.054) had lower EFS. Furthermore, PBSCT significantly improved EFS in patients with B symptoms (100% vs. 50.8%, P = 0.027) or bulky disease (100% vs. 52.8%, P = 0.045) when applied as an up-front strategy. Based on these results, we conclude that, for patients with specific adverse factors such as B symptoms and bulky disease, PBSCT was superior to conventional chemotherapy in terms of EFS.
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Linfoma Anaplásico de Células Grandes/cirugía , Trasplante de Células Madre de Sangre Periférica , Proteínas Tirosina Quinasas Receptoras/metabolismo , Adolescente , Adulto , Factores de Edad , Anciano , Quinasa de Linfoma Anaplásico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Niño , Terapia Combinada , Ciclofosfamida/uso terapéutico , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Linfoma Anaplásico de Células Grandes/tratamiento farmacológico , Linfoma Anaplásico de Células Grandes/patología , Linfoma Anaplásico de Células Grandes/radioterapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Prednisona/uso terapéutico , Inducción de Remisión , Estudios Retrospectivos , Tasa de Supervivencia , Vincristina/uso terapéutico , Adulto JovenRESUMEN
To further explore the role of rituximab when added to the CHOP-like regimen in the treatment of immunohistochemically defined non-germinal center B-cell subtype (non-GCB) diffuse large B-cell lymphoma(DLBCL), 159 newly diagnosed DLBCL patients were studied retrospectively based on the immunohistochemical evaluation of CD10, Bcl-6, MUM-1, and Bcl-2. Altogether, 110 patients underwent the CHOP-like regimen, and rituximab was added for the other 49 patients. Cox regression analysis showed that compared with the CHOP-like regimen, the rituximab-based regimen(R-CHOP regimen) significantly decreased the risk of disease relapse and progression in CD10-negative patients (P=0.001), Bcl-6-negative patients (P=0.01), and MUM-1-positive patients (P=0.003). The risk of disease relapse in patients with non-GCB subtype (P=0.002) also decreased. In contrast, patients with the opposite immunohistochemical marker expression profile and GCB subtype did not benefit from treatment with the R-CHOP regimen. In addition, non-GCB subtype patients had a significantly higher expression rate of Bcl-2 than GCB subtype patients (P=0.042). Although univariate analysis found that both Bcl-2-positive and -negative patients had significantly higher event-free survival rates with the R-CHOP regimen, only Bcl-2 positivity (P=0.004) maintained significance in the Cox regression analysis. We conclude that the addition of rituximab can significantly improve the prognosis of patients with non-GCB subtype DLBCL, which is closely related to the expression of CD10, Bcl-6, MUM-1, and Bcl-2.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ciclofosfamida/uso terapéutico , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapéutico , Femenino , Estudios de Seguimiento , Centro Germinal/patología , Humanos , Factores Reguladores del Interferón/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Neprilisina/metabolismo , Prednisona/uso terapéutico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Proto-Oncogénicas c-bcl-6/metabolismo , Recurrencia , Estudios Retrospectivos , Rituximab , Tasa de Supervivencia , Vincristina/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: To explore the effects of icotinib on the proliferation and apoptosis of various lung cancer cell lines. METHODS: Human lung cancer cell lines HCC827, H1650, H1975, A549 and human epidermal cancer cell line A431 were treated in vitro with icotinib or gefitinib at a concentration gradient of 0 - 40 µmol/L. Their proliferation effects were analyzed by the thiazolyl blue (MTT) assay and the apoptotic effects detected by flow cytometer. The downstream signaling proteins were detected by Western blot. RESULTS: The median inhibitory concentrations (IC(50)) of icotinib for A431 and HCC827 cell lines were (0.04 ± 0.02) and (0.15 ± 0.06) µmol/L respectively. No significant differences existed between the inhibitions of gefitinib and icotinib on A431, HCC827, H1650, H1975 and A549 cell lines (all P > 0.05). Compared with H1650, H1975 and A549 cell lines, icotinib significantly inhibited A431 (P = 0.009, 0.005 and 0.000) and HCC827 (P = 0.001, 0.001 and 0.000) cell lines. And it lowered the expressions of p-AKT, p-ERK and survivin protein expression through the inhibited activity of p-EGFR protein. CONCLUSION: Icotinib can arrest the proliferation of lung adenocarcinoma cells with EGFR mutation or over-expression by inhibiting the signal pathways of AKT-ERK and survivin.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Éteres Corona/farmacología , Quinazolinas/farmacología , Línea Celular Tumoral , Receptores ErbB/metabolismo , Gefitinib , Humanos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , SurvivinRESUMEN
OBJECTIVE: To compare the chemotherapeutic efficacies of third-generation plus platinum doublets in advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 1112 patients were diagnosed as advanced NSCLC at Chinese Academy of Medical Science and Cancer Hospital from January 2005 to August 2009. Their clinical efficacies and regimen compositions were retrospectively analyzed. All calculations were performed by SPSS 17.0. RESULTS: Differences in objective response rate (ORR) existed among four third-generation agents (paclitaxel, gemcitabine, vinorelbine and docetaxel) plus platinum doublets. Their ORRs were 35.6%, 35.4%, 25.9% and 37.4% respectively (χ(2) = 16.331, P = 0.001). And vinorelbine doublets had the lowest ORR (all P < 0.01). The ORRs of cisplatin and carboplatin doublets were 35.2% and 33.5% respectively. There was no difference in ORR among them (χ(2) = 0.352, P = 0.569). Subgroup analysis showed that the ORRs of four third generation plus platinum doublets were 34.8%, 35.3%, 23.2% and 37.1% in non-agers. And the vinorelbine doublets performed the worst. In the patients with squamous-cell lung cancer, the ORRs of paclitaxel and gemcitabine doublets were 45.5% and 28.4% respectively. And the paclitaxel doublets had the better performance (χ(2) = 5.250, P = 0.026). When combined with carboplatin, the ORRs of four doublets were 36.2%, 16.7%, 15.4% and 32.0% respectively. And the paclitaxel regimen was more effective than the gemcitabine and vinorelbine regimens (P = 0.018 and P = 0.034). The influences of subsequent therapy were nullified when the progression-free survival (PFS) was analyzed. The PFSs of these doublets were (3.67 ± 0.19), (2.95 ± 0.18), (3.05 ± 0.36) and (3.40 ± 0.37) months respectively. There was no difference among them. Pairwise comparisons showed that the mean PFS of patients on paclitaxel doublets was longer than those on gemcitabine doublets. And their PFSs were (3.67 ± 0.19) and (2.95 ± 0.18) months respectively (χ(2) = 7.037, P = 0.008). The PFSs of cisplatin and carboplatin doublets were (3.05 ± 0.14) and (3.65 ± 0.20) months respectively. The patients on carboplatin doublets had a longer PFS than that of those on cisplatin doublets (χ(2) = 6.012, P = 0.014). CONCLUSIONS: No difference exist in ORRs among different third-generation plus platinum doublets. But as the first-line treatment of advanced NSCLC, carboplatin doublets is superior to cisplatin doublets in terms of PFS.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Platino/administración & dosificación , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the mutations of epidermal growth factor receptor (EGFR) in tumor tissue and pleural effusion in advanced non-small cell lung cancer (NSCLC) patients, and to analyze the relationship between EGFR mutations and the clinicopathologic characteristics. METHODS: Two-hundred and forty-one cases of formalin-fixed, paraffin-embedded tumor tissues and 14 paired pleural effusions from advanced NSCLC patients were collected. Twenty-nine different EGFR mutations in exons 18-21 were assessed by scorpions and amplification refractory mutation system (scorpions ARMS) using real time PCR. The relationship between the EGFR mutations and clinical parameters was analyzed using statistical methods. EGFR mutation of 37 cases were detected with direct sequencing, and assessed the sensitivity, the specificity and the accuracy of scorpions ARMS. RESULTS: EGFR somatic mutations were detected in 114 of 234 advanced NSCLC patients, with the mutation rate of 48.7%, including deletions in exon 19 in 65 patients and point mutation of L858R in exon 21 in 39 patients; both accounting for 91.2% (104/114) of all types of EGFR mutations. The test results of 14 paired pleural effusion specimens were entirely the same to the tissues. The concordance rate of 2 different detection methods was 94.6%. Mutation rate was higher in women (55.9%) than in men (42.2%), and there was no difference in mutation rates between smokers and non-smokers; patients in stage IIIB and stage IV; adenocarcinoma and non-adenocarcinoma. CONCLUSIONS: EGFR somatic mutations appear to occur frequently in Chinese. Scorpions ARMS technology is a sensitive method to detect EGFR mutations and is suitable for screening patients who would likely respond to EGFR inhibitors therapy.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Eliminación de Gen , Neoplasias Pulmonares/genética , Mutación Puntual , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/metabolismo , Exones , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Adulto JovenRESUMEN
OBJECTIVE: Due to the rarity of angioimmunoblastic T-cell lymphoma (AITL), very limited data concerning its incidence patterns and prognostic factors are available. This study aimed to explore the incidence, characteristics, survival outcomes, and prognostic factors of AITL. METHODS: Age-adjusted incidence and temporal trends were calculated based on 1247 AITL patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-13 database. A total of 1525 AITL patients from the SEER-18 database and 43 patients from our single center were included for survival analysis and nomogram construction. RESULTS: The age-adjusted incidence for overall cohort was 0.123 [95% confidence interval (CI), 0.117-0.131) per 100 000 during 1992-2017. The overall incidence increased steeply at the rate of 15.3% (95%CI 11.0%-19.8%, P<0.001) per year during 1992-2004, but remained stable during 2004-2017 (P=0.200). Similar incidence trends were observed in age, sex, and stage subgroups. The final nomograms consisted of four variables: age at diagnosis, sex, Ann Arbor stage, and primary site. The concordance index (C-index) of the nomogram for 5-year overall survival prediction was 0.717, 0.690 and 0.820 in the training cohort, validation cohort-1 and cohort-2, respectively. Regarding the disease-specific survival (DSS), the nomogram also demonstrated a good discrimination level, with the C-index for predicting the probability of DSS at 5 years of 0.716, 0.682 and 0.813 for the three cohorts, respectively. The calibration displayed good concordance between the nomogram-predicted and actual observed outcomes. CONCLUSION: The age-adjusted incidence for AITL was low during 1992-2017. The incidence continuously increased during 1992-2004, but remained stable during 2004-2017. The nomograms as proposed may provide a favorable and accurate prognostic survival prediction in AITL.
Asunto(s)
Linfoma de Células T , Nomogramas , Humanos , Pronóstico , Incidencia , Análisis de SupervivenciaRESUMEN
OBJECTIVE: To explore the clinical factors affecting the sensitivity of EGFR-TKI treatment in advanced non-small cell lung cancer. METHODS: Clinical data were retrospective analyzed to determine the clinical factors affecting the outcome of 166 patients with advanced non-small cell lung cancer who received EGFR-TKI treatment in our hospttal from January of 2005 to December of 2006. RESULTS: One hundred and nineteen patients benefited from EGFR-TKI treatment in the total of 166 patients and the disease control rate was 71.7%. Among the factors analyzed, sex, age, smoking, pathological type, brain and bone metastasis or not when EGFR-TKI was used, the time using EGFR-TKI and the level of LDH at the time of diagnosis had no significant effect on the clinical benefit rate. Among the 126 patients with serum CEA assayed at diagnosis, 84 cases had a higher serum CEA level. Compared with the patients with normal serum CEA level, the patients with a higher serum CEA level benefited more easily from EGFR-TKI therapy, with a disease control rate of 79.8% and 59.5%, respectively (P = 0.016). Among the patients who got benefits from EGFR-TKI treatment, smoking and the CEA level at diagnosis had effects on the duration of progression-free survival. The progression free survivals were 9.57 ± 6.75 months in non-smokers, 4.86 ± 3.44 months in light-smokers and 5.25 ± 4.34 months in heavy-smokers (P = 0.007). The progression free survival was 9.45 ± 7.48 months in the group with a higher serum CEA level and 6.52 ± 4.46 months in the group with normal serum CEA level (P = 0.036). CONCLUSIONS: In patients with advanced non-small cell lung cancer, EGFR-TKIs treatment is safe and effective. The patients with high CEA level are prone to benefit from it.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/secundario , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/secundario , Antígeno Carcinoembrionario/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/secundario , Supervivencia sin Enfermedad , Clorhidrato de Erlotinib , Femenino , Estudios de Seguimiento , Gefitinib , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Retrospectivos , FumarRESUMEN
OBJECTIVE: To analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer (NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC. METHODS: Ninety-nine cases were enrolled in this study. Pathological tissue specimens and paired peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene mutation were detected by direct sequencing. The concentration of plasma EGFR protein was detected by ELISA. Univariate and multivariate statistical analyses of the efficacy and survival were performed using SPSS 13.0 software. RESULTS: The response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was 55.42 µg/L. The RR and CBR of patients with EGFR gene mutation was significantly higher than those without mutation (65.7% vs. 43.8%, P = 0.037; 94.3% vs. 71.9%, P = 0.008). The median PFS was prolonged (23 months vs. 10 months, P = 0.014). The CBR of patients with high EGFR protein expression (concentration ≥ 55.42 µg/L) was significantly higher than those with low expression (90.0% vs 64.1%, P = 0.004), and the median PFS was prolonged (21 months vs. 8 months, P = 0.016). EGFR protein level was an independent factor affecting the EGFR gene mutation status. The Correlation between EGFR gene mutation status and EGFR protein level was positive. CONCLUSIONS: Gefitinib is effective in the treatment of advanced NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR protein level in peripheral blood may be a molecular biomarker in prediction of efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.
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Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB/genética , Neoplasias Pulmonares , Quinazolinas/uso terapéutico , Anciano , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Supervivencia sin Enfermedad , Receptores ErbB/sangre , Exones , Femenino , Estudios de Seguimiento , Gefitinib , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To analyze the outcome of platinum analogue-based chemotherapy for advanced esophageal squamous cell carcinoma (ESCC) patients treated in Cancer Hospital of Chinese Academy of Medical Science. The association of response rate or OS and the clinical-pathological factors were analyzed as well. METHODS: Clinical data of 134 advanced ESCC were retrospectively analyzed from January 1999 to August 2008 in our hospital. All of these chemo-naive patients received platinum analogue-based chemotherapy. The association of response rate or OS and the clinical-pathological factors were analyzed. RESULTS: The median age of all the 134 patients was 58 years old. The ratio of male and female was 7.9:1. A total of 450 cycles (median: 3 cycles) of chemotherapy was completed. 91 (67.9%) of these patients received cisplatin-based regimens. The overall response rate was 31.3%, and cisplatin-based regimens were better than other platinum analogue-based regimen, but there was no significant difference (36.3% vs 20.9%, P = 0.075). The median follow-up time was 44 months (range 8 - 120). The median TTP was 4 months (range 1 - 43), and median survival time was 8 months (range 1 - 43). The 1 year and 2 year survival rate was 36.2% and 17.5%, respectively. According to univariate analysis, there was a worse prognosis when patients with multiple primary site, well-differentiated tumor, more than one site of metastasis, fail to achieve responses, TTP ≤ 4 months and received less than 2 cycles of chemotherapy. Multivariate analysis showed that TTP ≤ 4 months was the only independent prognostic factor for this group of patients. CONCLUSIONS: Platinum analogue-based chemotherapy was the standard of care for advanced ESCC. There was a trend to improve the outcomes with platinum analogue combined with new drugs. Randomized trial with large samples was need.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Platino/administración & dosificación , Compuestos de Platino/uso terapéutico , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To characterize the safety profiles and serum pharmacokinetic effects of anti-epidermal growth factor receptor monoclonal antibody (CMAB009) in advanced cancer patients and evaluate the preliminary evidence of its anti-tumor activity. METHODS: This phase I, single-center clinical trial had 2 phases of treatment: single-dose phase, followed by a fixed weekly dose. Subjects meeting the inclusion criteria were enrolled. The subjects were randomly assigned to receive 1 of 3 initial doses of CMAB009 (100, 250 & 400 mg/m(2)) for the purpose of single-dose pharmacokinetic evaluation. After a 28-day washout period of allowing for the characterization of pharmacokinetic end points, the eligible patients were permitted to undergo a successive multi-dose phase study. They were divided into 2 dose groups, group A with 4 weekly doses of 250 mg/m(2), group B with the initial dose of 400 mg/m(2), followed by 3 weekly doses of 250 mg/m(2). The subjects were closely monitored for adverse events throughout the trial. RESULTS: A total of 18 subjects were recruited, including colorectal cancer (n = 10), non-small cell lung cancer (n = 7) and gastric cancer (n = 1). CMAB009-associated toxicity was minimal. And the most commonly reported Grade 1/2 adverse events were skin rashes, fever, nausea and headache. Two patients with colorectal cancer achieved partial remission and the time to progression (TTP) was 24 and 16 weeks respectively. CONCLUSION: As a well-tolerated antitumor agent, CMAB009 may be safely administered by the above multi-dosing protocol.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Pulmón de Células no Pequeñas , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fiebre , HumanosRESUMEN
OBJECTIVE: To analyze the treatment efficacy after a failed regimen of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in patients with advanced non-small cell lung carcinoma (NSCLC). METHODS: A retrospective analysis was conducted for 87 patients with advanced NSCLC at our hospital from January of 2005 to December of 2006. All subjects received chemotherapy after a failure of EGFR-TKI, there were 37 cases of male and the median age was 56 ± 11 (range, 31 - 76) years, 50 cases of female, median age 56 ± 13 (range, 31 - 78) years; They received a 2-drug combination chemotherapy (n = 61) and a monodrug chemotherapy (n = 26). The primary endpoint was overall survival (OS). And the secondary endpoints were objective response rate (ORR) and side effects. RESULTS: The OS was 9.4 ± 6.0 (range, 2-33) months and ORR 9.2% (8/87). The OS was 9.1 ± 5.2 (range, 2 - 31) months in combination chemotherapy group and 10.0 ± 7.3 (range, 3 - 33) months in monodrug group; the ORRs were 11.5% (7/61) and 3.8% (1/26) respectively in two groups. There was no significant difference in OS and ORR between two groups (P > 0.05). The common side effects were myelosuppression and nausea/vomiting. The rate of myelosuppression was 87.4% (76/87) and that of 3/4 grade myelosuppression 33.3% (29/87). And the rate of nausea/vomiting was 86.2% (75/87) and that of 3/4 grade nausea/vomiting 10.3% (9/87). Other side effects were mild and well-tolerated. CONCLUSION: If tolerated, chemotherapy after an EGFR-TKI failure may prolong the survival in advanced NSCLC patients.