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BACKGROUND: Objectively measured circulating biomarkers of prognosis complementing existing clinicopathological models are needed in renal cell carcinoma (RCC). METHODS: Blood samples collected from 216 RCC patients in Leeds before nephrectomy (median follow-up 7 years) were analysed for C-reactive protein (CRP), osteopontin (OPN) and carbonic anhydrase IX (CA9) and prognostic significance determined. RESULTS: CA9, OPN and CRP were univariately prognostic for overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) with CRP and CA9 being independently prognostic for OS/CSS and OS, respectively. Including CA9, OPN and CRP with other conventional prognostic factors gave a superior predictive capacity when compared with a previously published pre-operative clinical nomogram (Karakiewicz et al, 2009). Osteopontin outperformed this nomogram and the post-operative SSIGN score for OS but not for CSS, being significantly predictive for non-cancer deaths. Osteopontin, CRP and CA9 outperformed stage (c-index 76% compared with 70% for stage) and OPN or CA9 identified several subsets of poor prognosis patients including in T1 patients, who may benefit from adjuvant therapy and increased surveillance. CONCLUSION: Circulating CA9, OPN and CRP add value to existing clinicopathological prognostic factors/models and support further studies to investigate their potential use in improving the clinical management of RCC.
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Biomarcadores de Tumor/sangre , Proteína C-Reactiva/metabolismo , Anhidrasa Carbónica IV/sangre , Carcinoma de Células Renales/sangre , Neoplasias Renales/sangre , Osteopontina/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/enzimología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Renales/enzimología , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , PronósticoRESUMEN
BACKGROUND: Literature reviews of cancer trials have highlighted the need for better understanding of phase II statistical designs. Understanding the key elements associated with phase II design and knowledge of available statistical designs is necessary to enable appropriate phase II trial design. METHODS: A systematic literature review was performed to identify phase II trial designs applicable to oncology trials. The results of the review were used to create a library of currently available designs, and to develop a structured approach to phase II trial design outlining key points for consideration. RESULTS: A total of 122 papers describing new or adapted phase II trial designs were obtained. These were categorised into nine levels, reflecting the practicalities of implementation, and form a library of phase II designs. Key design elements were identified by data extraction. Along with detailed description of the key elements and the library of designs, a structured thought process was developed to form a guidance document for choice of phase II oncology trial design. CONCLUSION: The guidance offers researchers a structured and systematic approach to identifying phase II trial designs, highlighting key issues to be considered by both clinicians and statisticians and encouraging an interactive approach to more informed trial design.
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Ensayos Clínicos Fase II como Asunto/métodos , Guías como Asunto , Neoplasias/terapia , Proyectos de Investigación , Algoritmos , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricosRESUMEN
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10-7), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10-14) and 1.68 (P=2.18 × 10-14), respectively. Patients with 'double-hit' defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10-27) for all patients and 3.19 (P=1.23 × 10-18) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10-15), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P<0.0001) or gain(11q25) and CCND1 overexpression (P<0.0001). Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment.
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Mieloma Múltiple/diagnóstico , Mieloma Múltiple/patología , Adulto , Anciano , Anciano de 80 o más Años , Aberraciones Cromosómicas , Deleción Cromosómica , Ensayos Clínicos Fase III como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , Modelos de Riesgos Proporcionales , Translocación Genética/genética , Trasplante Autólogo/métodosRESUMEN
PURPOSE: To determine whether interferon (IFN) -alpha2, when given with or following chemotherapy, influences response rate, remission duration, and survival in newly diagnosed patients with follicular lymphoma. PATIENTS AND METHODS: Ten phase III studies evaluating the role of IFN-alpha2 in 1,922 newly diagnosed patients with follicular lymphoma were analyzed. Updated individual patient data were used to perform meta-analyses for response, survival, and remission duration. RESULTS: The addition of IFN-alpha2 to initial chemotherapy did not significantly influence response rate. An overall meta-analysis for survival showed a significant difference in favor of IFN-alpha2, but also showed significant heterogeneity between studies. Further analyses were carried out in order to explain this heterogeneity, and to define the circumstances in which IFN-alpha2 prolonged survival. The survival advantage was seen when IFN-alpha2 was given: (1) in conjunction with relatively intensive initial chemotherapy (2P = .00005), (2) at a dose >/= 5 million units (2P = .000002), (3) at a cumulative dose >/= 36 million units per month (2P = .000008), and (4) with chemotherapy rather than as maintenance therapy (P = .004). With regard to remission duration, there was also a significant difference in favor of IFN-alpha2, irrespective of the intensity of chemotherapy used, IFN dose, or whether IFN was given as a maintenance strategy or with chemotherapy. CONCLUSION: When given in the context of relatively intensive initial chemotherapy, and at a dose >/= 5 million units (>/= 36 x 10(6) units per month), IFN-alpha2 prolongs survival and remission duration in patients with follicular lymphoma.
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Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Interferón-alfa/uso terapéutico , Linfoma Folicular/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ensayos Clínicos Fase II como Asunto , Esquema de Medicación , Femenino , Humanos , Interferón alfa-2 , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: This phase III randomized trial compared two chemotherapy regimens, gemcitabine plus carboplatin and mitomycin, ifosfamide, and cisplatin, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC). The regimens were compared with regard to effects on survival, response rates, toxicity, and quality of life. PATIENTS AND METHODS: Eligible patients had previously untreated stage IIIB or IV NSCLC suitable for cisplatin-based chemotherapy. Randomly assigned patients were to receive four cycles, each at 3-week intervals, of carboplatin area under the curve of 5 on day 1 plus gemcitabine 1,200 mg/m(2) on days 1 and 8 (GCa) or mitomycin 6 mg/m(2), ifosfamide 3g/m(2), and cisplatin 50 mg/m(2) on day 1 (MIC). RESULTS: Between February 1999 and August 2001, 422 patients (GCa, n = 212; MIC, n = 210) were randomly assigned in the United Kingdom. The majority of patients received the intended four cycles (GCa, 64%; MIC, 61%). There was a significant survival advantage for GCa compared with MIC (hazard ratio, 0.76; 95% CI, 0.61 to 0. 93; P = .008). Median survival was 10 months with GCa and 7.6 months with MIC (difference, 2.4 months; 95% CI, 1.0 to 4.0), and 1-year survival was 40% with GCa and 30% with MIC (difference, 10%; 95% CI, 3% to 18%). Overall response rates were similar (42% for GCa v 41% for MIC; P = .84). More thrombocytopenia occurred with GCa (P = .03), but this was not associated with increased hospital admission or fatality. GCa caused less nausea, vomiting, constipation, and alopecia and was associated with fewer admissions for administration and better quality of life. CONCLUSION: In patients with advanced NSCLC, GCa chemotherapy was shown to be a better-tolerated treatment that conferred a survival advantage over MIC.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibióticos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos Alquilantes/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Femenino , Humanos , Ifosfamida/administración & dosificación , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Calidad de Vida , Tasa de Supervivencia , Resultado del Tratamiento , GemcitabinaRESUMEN
A mathematical model is presented which seeks to determine, from examination of the response durations of a group of patients with malignant disease, the mean and distribution of the resistant tumor volume. The mean tumor-doubling time and distribution of doubling times are also estimated. The model assumes that in a group of patients there is a log-normal distribution both of resistant disease and of tumor-doubling times and implies that the shapes of certain parts of an actuarial response-duration curve are related to these two factors. The model has been applied to data from two reported acute leukemia trials: (a) a recent acute myelogenous leukemia trial was examined. Close fits were obtained for both the first and second remission-duration curves. The model results suggested that patients with long first remissions had less resistant disease and had tumors with slower growth rates following second line treatment; (b) an historical study of maintenance therapy for acute lymphoblastic leukemia was used to estimate the mean cell-kill (approximately 10(4) cells) achieved with single agent, 6-mercaptopurine. Application of the model may have clinical relevance, for example, in identifying groups of patients likely to benefit from further intensification of treatment.
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Matemática , Modelos Biológicos , Neoplasias/terapia , Recurrencia , Humanos , Inducción de RemisiónRESUMEN
BACKGROUND: Stage I non-small cell lung cancer (NSCLC) is potentially curable, and surgery is considered to be the standard of care for patients with good performance status and minimal co-morbidity. However, a significant proportion of patients with stage I NSCLC have a poorer performance status and significant medical co-morbidity that make them at higher risk of morbidity and mortality from surgery. Stereotactic ablative radiotherapy (SABR), which uses modern radiotherapeutic techniques to deliver large doses of radiation, has shown superiority over conventional radiotherapy in terms of local control and toxicity and is a standard of care for patients with stage I NSCLC who are at too high risk for surgery. However, it is not known whether surgery or SABR is the most effective in patients with stage I NSCLC who are suitable for surgery but are less fit and at higher risk surgical complications. Previous randomised studies have failed to recruit in this setting, and therefore, a feasibility study is required to see whether a full randomised control trial would be possible. METHODS/DESIGN: SABRTooth is a UK-based, multi-centre, open-label, two-group individually (1:1) randomised controlled feasibility study in patients with peripheral stage I NSCLC considered to be at higher risk from surgical resection. The study will assess the feasibility of conducting a definitive large-scale phase III trial. The primary objective is to assess recruitment rates to provide evidence that, when scaled up, recruitment to a large phase III trial would be possible; the target recruitment being 54 patients in total, over a 21-month period. There are multiple secondary and exploratory objectives designed to explore the optimum recruitment and data collection strategies to help optimise the design of a future phase III trial. DISCUSSION: To know whether SABR is a better, equivalent or inferior alternative to surgery for higher risk patients is a key question in lung cancer. Other studies comparing SABR to surgery have closed early due to poor recruitment, and therefore, the SABRTooth feasibility study has been designed around the UK National Health Service (NHS) cancer pathway incorporating many design features in order to maximise recruitment for a future definitive phase III trial. TRIAL REGISTRATION: controlled-trials.com ISRCTN13029788.
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[This corrects the article DOI: 10.1186/s40814-016-0046-2.].
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We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4-1.0%), 2.3% (95% CI 1.6-2.7%) and 3.8% (95% CI 2.9-4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2-26.4%), compared with 6.5% (95% CI 0.2-12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Neoplasias Primarias Secundarias/tratamiento farmacológico , Talidomida/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Bortezomib/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Ácidos Hidroxámicos , Estimación de Kaplan-Meier , Lenalidomida , Masculino , Persona de Mediana Edad , Mieloma Múltiple/epidemiología , Mieloma Múltiple/patología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/patología , Oligopéptidos/administración & dosificación , Factores de Riesgo , Talidomida/administración & dosificación , VorinostatRESUMEN
A mathematical model has been applied to patients with small-cell lung cancer (SCLC) in order to estimate the proportions of resistant and sensitive tumor at presentation, and the efficacy of the treatment, measured in terms of proportions of tumor killed with each cycle of therapy. The model uses estimates of tumor volume obtained from computed tomographic (CT) scans of the chest before each course of chemotherapy. Application of the model to a trial using single-agent high-dose cyclophosphamide (HDC) showed that HDC killed approximately 94% of the sensitive tumor on each application, but that the proportion of tumor resistant to HDC rose from an average of 1% to an average of 15% after the first cycle, assuming a 30-day tumor doubling time. These estimates proved fairly insensitive to different assumptions about tumor doubling time and inaccuracies in volume measurement and may thus provide a useful additional evaluation technique for some clinical trials.
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Carcinoma de Células Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Carcinoma de Células Pequeñas/patología , Ciclofosfamida/uso terapéutico , Resistencia a Medicamentos , Humanos , Neoplasias Pulmonares/patología , Matemática , Modelos BiológicosRESUMEN
PURPOSE: A meta-analysis was performed to compare survival after treatment with melphalan and prednisolone (M + P) with that after combination chemotherapy (CCT) in patients with multiple myeloma. METHODS: Meta-analysis was performed on 18 published trials comprising 3,814 patients comparing M + P with CCT. Two-year survival percentages with observed and expected deaths at 2 years were calculated for each trial, and the overview methodology was applied to these figures. RESULTS: Overall results from the 18 trials suggest that there is no difference in efficacy between the two treatments. This finding, however, masks a highly significant correlation between 2-year survival rates for M + P-treated patients in individual studies and the difference between the M + P and CCT 2-year survival rates for that study (r = .69; P = .0008). In separate overviews, those studies with a high M + P 2-year survival rate showed a survival difference in favor of M + P (P = .02), whereas those with a low rate suggested a difference in favor of CCT (P V .07). Comparison of the 2-year survival rates in the M + P treatment arms of each of the studies with available data showed an inverse correlation between survival and the proportion of patients with either poor performance status (P less than .001) or immunoglobulin A (IgA) M band (P = .02). CONCLUSIONS: These results imply that M + P is superior for patients with an intrinsically good prognosis and inferior for those patients with a poor prognosis. If reliable prognostic factors can be established for this disease, they could be used to select therapy for individual patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Melfalán/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Prednisolona/administración & dosificación , Análisis Actuarial , Humanos , Metaanálisis como Asunto , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de SupervivenciaRESUMEN
PURPOSE: To determine in a randomized trial of advanced ovarian carcinoma whether consolidation therapy with whole-abdominal radiotherapy (RT) after chemotherapy improves survival and disease-free survival compared with the continued chemotherapy. PATIENTS AND METHODS: Two hundred fifty-four patients with advanced epithelial ovarian cancer (stages IIB to IV) were entered onto a study of five monthly courses of 400 mg/m2 of carboplatin. One hundred seventeen patients with residual disease of 2 cm or less at second-look laparotomy or laparoscopy were then randomized to receive consolidation therapy, either five further courses of carboplatin at the same dosage or whole-abdominal RT (24 Gy). There was no control arm. RESULTS: Chemotherapy was well tolerated and was usually administered on an outpatient basis. Myelosuppression that was sufficient to delay chemotherapy occurred in only 3% of 1,418 courses analyzed. The main toxicity of carboplatin was nausea and vomiting, but this was easier to control than that with cisplatin. Although RT was well tolerated in the majority of the 58 patients, one patient who had been found to have multiple adhesions at second-look surgery developed fecal fistulae post-RT that resulted in the patient's death from peritonitis. Median survival for the whole group from date of surgery was 25 months. No statistical difference was found in either survival or disease-free survival between those patients who received consolidation chemotherapy and those who were treated with abdominal RT. Prognostic factors used to assess survival were stage, histology, amount of residual disease after primary surgery, and presence of tumor at second-look surgery. CONCLUSION: There seems to be no significant advantage for consolidation whole-abdominal RT compared with the continuation of the same chemotherapy in the management of advanced epithelial carcinoma of the ovary, even when no macroscopic residual disease is apparent at second-look surgery.
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Carboplatino/uso terapéutico , Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/radioterapia , Adolescente , Adulto , Anciano , Carboplatino/efectos adversos , Terapia Combinada , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Modelos de Riesgos Proporcionales , Radioterapia/efectos adversos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Pequeñas/tratamiento farmacológico , Etopósido/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Pequeñas/patología , Carcinoma de Células Pequeñas/radioterapia , Ensayos Clínicos como Asunto , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Etopósido/farmacocinética , Etopósido/uso terapéutico , Semivida , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/radioterapia , Tasa de Depuración Metabólica , Distribución Aleatoria , Vincristina/administración & dosificaciónRESUMEN
Eighteen patients with untreated small-cell cancer of the lung have been treated with cyclophosphamide 200 mg/kg on two occasions at an interval of four weeks. An additional eight patients received etoposide in addition to cyclophosphamide. Measurements of tumor volume were made by thoracic computed tomographic (CT) scan before and after each cycle. When compared with our previous study in which only one cycle of cyclophosphamide was given, the double procedure did not increase response rate, decrease the incidence of local relapse, or prolong the relapse-free interval. Survival after relapse was shorter with two cycles of chemotherapy mainly due to greater difficulty in administering further chemotherapy. The CT scans showed a decrease in tumor volume from 99.2 cc to 21 cc after the first cycle, but a smaller decrease to 14.1 cc after the second. These results show that the rapid emergence of drug resistance imposes limitations on the use of very high-dose cytotoxic chemotherapy.
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Carcinoma de Células Pequeñas/tratamiento farmacológico , Ciclofosfamida/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Trasplante de Médula Ósea , Carcinoma de Células Pequeñas/diagnóstico por imagen , Carcinoma de Células Pequeñas/mortalidad , Ensayos Clínicos como Asunto , Ciclofosfamida/efectos adversos , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/mortalidad , Masculino , Mesna/administración & dosificación , Persona de Mediana Edad , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
Since 1978, 187 patients (age range, 15 to 59, median 44 years) have received short-term chemotherapy as part of three sequential open studies (B-IX, X, Xb) or a randomized clinical trial (B-XI). An intended six cycles of Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), cytarabine (ara-C), and thioguanine (TG) were administered with as short an intercycle time as possible. No further therapy was administered. Complete remission (CR) was achieved in 118 of 187 patients (63%). On univariate and multivariate analyses achievement of CR correlated adversely with a low serum albumin at presentation and an antecedent marrow disorder. Forty-five patients continue in first remission between 15 months and 8 1/2 years, no relapses being seen after 3 1/2 years (median follow-up, 3 1/2 years). The median duration of remission was 1 year. M3 morphology, a blast count less than 100 x 10(9)/L, and absence of hepatosplenomegaly correlated favorably with remission duration. There was no difference in duration of remission between patients receiving 3, 4, 5, or 6 cycles. The best results overall were achieved in patients under the age of 40, with 43% projected to remain free of disease at 5 years. Fifty patients remain alive between 17 months and 9 years, the predicted actuarial survival being 25% at 5 years.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Análisis Actuarial , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Citarabina/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Inducción de RemisiónRESUMEN
One hundred forty-eight patients with newly diagnosed follicular lymphoma were treated over a 12-year period. Twenty-two patients received radiotherapy for stage I and II disease, followed by adjuvant chemotherapy in 14 patients. One hundred thirteen were treated at presentation with short courses of chemotherapy, most often with single-agent chlorambucil for bulky stage II and stages III and IV disease. Thirteen patients were managed expectantly until there was evidence of disease progression. The median survival was 9 years. Patients treated with radiotherapy for stage I and II disease had an 83% relapse-free survival, but those with bulky stage II or stages III and IV disease treated with chemotherapy pursued a remitting and relapsing course with a 70% response rate at initial and subsequent retreatments, but a median duration of remission of 4 years in stage III and 1 year in stage IV disease (P = .041). Patients were observed in relapse and retreatment was administered as appropriate, once every 33 months on average. Poor prognosis patients could be identified by a combination of the presentation characteristics: B symptoms, hepatosplenomegaly, anemia, and abnormal liver function. These factors predicted a poor response to treatment and correlated with a short survival. Histologic subgroups were not associated with differences in survival, but transformation to a diffuse high-grade lymphoma was observed in 23 of the 72 patients (32%) at risk, with a median follow-up of 6 years and 6 months, and was associated with a very poor prognosis. The present treatment strategy has proved successful for most patients with localized disease and those older patients with indolent small volume disseminated follicular lymphoma. New approaches are being investigated for the younger poor prognosis patients.
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Linfoma Folicular/patología , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clorambucilo/uso terapéutico , Femenino , Hepatomegalia/patología , Humanos , Enfermedades Linfáticas/patología , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/radioterapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Distribución Aleatoria , Esplenomegalia/patologíaRESUMEN
PURPOSE: A prospective randomized trial to determine if granulocyte colony-stimulating factor (G-CSF) could increase the received dose-intensity (RDI) of weekly chemotherapy in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Forty patients with SCLC with good prognostic features (all patients with limited disease [LD], and extensive-disease [ED] patients with Eastern Cooperative Oncology Group [ECOG] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal) were randomized to receive weekly chemotherapy with or without G-CSF. G-CSF (5 micrograms/kg) was self-administered subcutaneously on days when chemotherapy was not given. Chemotherapy consisted of cisplatin 50 mg/m2 intravenously (IV) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV (with mesna) and doxorubicin 25 mg/m2 on day 1, for a total of 12 courses. Dose modifications (dose reductions and treatment delays) were made according to defined hematologic criteria. RESULTS: Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm (P = .20). The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm (nine of 17) compared with the G-CSF arm (four of 23, P < .04). Cycle delays due to leukopenia were similar in both arms of the study. The RDI was 82% of projected in the control arm (95% confidence interval [CI], 79% to 84%) and 84% in patients receiving G-CSF (95% CI, 82% to 87%) (P value not significant). CONCLUSION: In this randomized trial, G-CSF significantly decreased dose reductions due to neutropenia. However, administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity. Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedades de la Médula Ósea/prevención & control , Carcinoma de Células Pequeñas/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Enfermedades de la Médula Ósea/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The prognosis of patients with tumours measuring up to 1 cm diameter was examined. 336 patients treated at Guy's Hospital between 1975 and 1994 were reviewed. Of these, 103 (31%) were lymph node-positive, with approximately one third of these having one node involved, one third two to three nodes and one third four nodes or more. A similar proportion of those with palpable and impalpable tumours had axillary node involvement. Patients with axillary node involvement had a significantly worse prognosis and those node-positive patients with impalpable cancers had a significantly worse outcome compared with node-positive palpable cases. When patients were subdivided on a basis of nodal status and age (< or = 50 or > 50), node-positive women aged > 50 fared significantly better than younger women. These data suggest the need to know accurately the axillary nodal status of patients with small breast cancers, whether symptomatic or detected by screening. This knowledge will allow women with curable cancers to be identified together with those who have a worse prognosis and who will be likely to benefit from systemic adjuvant therapy.
Asunto(s)
Neoplasias de la Mama/patología , Factores de Edad , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática/patología , Persona de Mediana Edad , Pronóstico , Análisis de SupervivenciaRESUMEN
The influence of scheduling of doxorubicin on response, survival and quality of life was assessed in a randomised trial in patients with advanced breast cancer, none of whom had previously received cytotoxic chemotherapy for advanced disease. 28 patients received 75 mg/m2 doxorubicin every 3 weeks for four courses (arm 1) and 31 patients received 25 mg/m2 weekly for 12 courses (arm 2). Response rates and median time to progression were similar in the two arms and median survival was 8 months in both arms. However, amongst patients receiving treatment every 3 weeks, psychological distress measured using the Rotterdam symptom checklist fell significantly over the course; no such change was observed in those treated weekly. Physical symptoms related to cancer improved during treatment similarly for both groups.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Calidad de Vida , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
One hundred lymph node biopsy specimens were examined on two separate occasions by seven pathologists differing in experience in lymphoreticular pathology. Neither history nor immunohistochemistry was provided and the study, therefore, focused on morphological interpretation alone. The participants evaluated each case using a constructed response form in which the confidence with which they entered each response was also entered. Agreement on various points, between pathologists, between the two rounds, and with the referring centre was assessed. Whilst there was a high level of agreement over a diagnosis of benign vs. malignant and non-Hodgkin lymphoma vs. Hodgkin's disease, there was considerably less agreement over both T vs. B cell phenotype and high vs. low grade. The lack of agreement over grade, an evaluation which is usually made independent of immunohistochemistry, is particularly important, because of the relevance to selection of treatment. Proliferation markers may be more appropriate determinants of treatment choice.