Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer.

BACKGROUND: AKT pathway activation is implicated in endocrine-therapy resistance. Data on the efficacy and safety of the AKT inhibitor capivasertib, as an addition to fulvestrant therapy, in patients with hormone receptor-positive advanced breast cancer are limited. METHODS: In a phase 3, randomized, double-blind trial, we enrolled eligible pre-, peri-, and postmenopausal women and men with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer who had had a relapse or disease progression during or after treatment with an aromatase inhibitor, with or without previous cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. Patients were randomly assigned in a 1:1 ratio to receive capivasertib plus fulvestrant or placebo plus fulvestrant. The dual primary end point was investigator-assessed progression-free survival assessed both in the overall population and among patients with AKT pathway-altered (PIK3CA, AKT1, or PTEN) tumors. Safety was assessed. RESULTS: Overall, 708 patients underwent randomization; 289 patients (40.8%) had AKT pathway alterations, and 489 (69.1%) had received a CDK4/6 inhibitor previously for advanced breast cancer. In the overall population, the median progression-free survival was 7.2 months in the capivasertib-fulvestrant group, as compared with 3.6 months in the placebo-fulvestrant group (hazard ratio for progression or death, 0.60; 95% confidence interval [CI], 0.51 to 0.71; P<0.001). In the AKT pathway-altered population, the median progression-free survival was 7.3 months in the capivasertib-fulvestrant group, as compared with 3.1 months in the placebo-fulvestrant group (hazard ratio, 0.50; 95% CI, 0.38 to 0.65; P<0.001). The most frequent adverse events of grade 3 or higher in patients receiving capivasertib-fulvestrant were rash (in 12.1% of patients, vs. in 0.3% of those receiving placebo-fulvestrant) and diarrhea (in 9.3% vs. 0.3%). Adverse events leading to discontinuation were reported in 13.0% of the patients receiving capivasertib and in 2.3% of those receiving placebo. CONCLUSIONS: Capivasertib-fulvestrant therapy resulted in significantly longer progression-free survival than treatment with fulvestrant alone among patients with hormone receptor-positive advanced breast cancer whose disease had progressed during or after previous aromatase inhibitor therapy with or without a CDK4/6 inhibitor. (Funded by AstraZeneca and the National Cancer Institute; CAPItello-291 ClinicalTrials.gov number, NCT04305496.).

Linfoma de células grandes T anaplásico: experiencia de 10 años en el Instituto Nacional de Enfermedades Neoplásicas, Lima - Perú / Anaplastic large T-cell lymphoma: 10-year experience at the National Institute of Neoplastic Diseases, Lima ­ Peru

Introducción: El Linfoma de Células Grandes T Anaplásico es una patología infrecuente, determinada por la expresión del CD30, con diferentes características en su presentación y ser de carácter más agresivos de acuerdo a la expresión del ALK. Objetivos: El presente estudio busca determinar las características epidemiológicas, clinicopatológicas y pronóstico de los pacientes con Linfoma de Células Grandes T Anaplásico. Métodos: Estudio descriptivo, retrospectivo de pacientes diagnosticados con Linfoma de Células Grandes T Anaplásico del Instituto Nacional de Enfermedades Neoplásicas (INEN) entre los años 2006 al 2016. Resultados: Se analizaron y revisaron la patología de 86 pacientes, 57% fueron hombres y 33% mujeres, de la población total 21,9% fueron positivos para ALK. 48 de los pacientes se encontraron en EC I y II y 36 entre estadios III y IV. 57 pacientes presentaban riesgo bajo o intermedio bajo mientras que 26 entre riesgo intermedio alto y alto. La sobrevida global estimada fue 40,8% a los 5 años, en el grupo de pacientes con ALK + fue 67,4% y en el grupo con ALK- se estimó en 30,2%. Conclusiones: El Linfoma de Células Grandes T Anaplásico es una enfermedad agresiva, con distribución heterogénea respecto a la edad y ligeramente más frecuente en varones, con el ALK y el índice pronóstico internacional como factores pronósticos importantes.

Introduction: Anaplastic Large T-Cell Lymphoma is an infrequent pathology, determined by the expression of CD30, with different characteristics in its presentation and being more aggressive according to the expression of ALK. Objectives: The present study seeks to determine the epidemiological, clinicopathological and prognostic characteristics of patients with Anaplastic Large T-Cell Lymphoma. Methods: Descriptive, retrospective study of patients diagnosed with Anaplastic Large T-Cell Lymphoma of the National Institute of Neoplastic Diseases (INEN) between 2006 and 2016. Results: The pathology of 86 patients was analyzed and reviewed, 57% were men and 33% women, of the total population 21.9% were positive for ALK. 48 of the patients were found in CD I and II and 36 between stages III and IV. 57 patients had low or low-intermediate risk, while 26 had high-intermediate and high risk. The estimated overall survival was 40.8% at 5 years, in the group of patients with ALK + it was 67.4% and in the group with ALK- it was estimated at 30.2%. Conclusions: Anaplastic Large T-Cell Lymphoma is an aggressive disease, with a heterogeneous distribution with respect to age and slightly more frequent in males, with ALK and the international prognostic index as important prognostic factors.

The current situation regarding the availability and accessibility of anticancer drugs for breast cancer in the Peruvian public health systems.

The availability of effective, accessible, safe and high-quality anticancer drugs for the medical treatment of cancer is fundamental in ensuring optimal healthcare in the public health system in Peru. The main objective is to assess the current situation regarding anticancer drugs (termed 'high-cost') for breast cancer, as well as an analysis of the possible factors which negatively impact access to the Peruvian public health systems.There are similarities in the availability of anticancer drugs, since most treatments are covered by the Peruvian Ministry of Health. EsSalud offers an extra monoclonal antibody (pertuzumab) in the metastatic treatment stage. Meanwhile, the National Institute of Neoplastic Diseases (INEN), mainly for metastatic disease, has relied on more tested treatments over the last year. An agreement has been reached with the armed forces, which will enable patients to receive oncology care at the INEN and, thereby, benefit from the use of high-cost drugs.

Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.

BACKGROUND: The use of adjuvant chemotherapy in patients with breast cancer may be guided by clinicopathological factors and a score based on a 21-gene assay to determine the risk of recurrence. Whether the level of clinical risk of breast cancer recurrence adds prognostic information to the recurrence score is not known. METHODS: We performed a prospective trial involving 9427 women with hormone-receptor-positive, human epidermal growth factor receptor 2-negative, axillary node-negative breast cancer, in whom an assay of 21 genes had been performed, and we classified the clinical risk of recurrence of breast cancer as low or high on the basis of the tumor size and histologic grade. The effect of clinical risk was evaluated by calculating hazard ratios for distant recurrence with the use of Cox proportional-hazards models. The initial endocrine therapy was tamoxifen alone in the majority of the premenopausal women who were 50 years of age or younger. RESULTS: The level of clinical risk was prognostic of distant recurrence in women with an intermediate 21-gene recurrence score of 11 to 25 (on a scale of 0 to 100, with higher scores indicating a worse prognosis or a greater potential benefit from chemotherapy) who were randomly assigned to endocrine therapy (hazard ratio for the comparison of high vs. low clinical risk, 2.73; 95% confidence interval [CI], 1.93 to 3.87) or to chemotherapy plus endocrine (chemoendocrine) therapy (hazard ratio, 2.41; 95% CI, 1.66 to 3.48) and in women with a high recurrence score (a score of 26 to 100), all of whom were assigned to chemoendocrine therapy (hazard ratio, 3.17; 95% CI, 1.94 to 5.19). Among women who were 50 years of age or younger who had received endocrine therapy alone, the estimated (±SE) rate of distant recurrence at 9 years was less than 5% (≤1.8±0.9%) with a low recurrence score (a score of 0 to 10), irrespective of clinical risk, and 4.7±1.0% with an intermediate recurrence score and low clinical risk. In this age group, the estimated distant recurrence at 9 years exceeded 10% among women with a high clinical risk and an intermediate recurrence score who received endocrine therapy alone (12.3±2.4%) and among those with a high recurrence score who received chemoendocrine therapy (15.2±3.3%). CONCLUSIONS: Clinical-risk stratification provided prognostic information that, when added to the 21-gene recurrence score, could be used to identify premenopausal women who could benefit from more effective therapy. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.

BACKGROUND: The recurrence score based on the 21-gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS: We performed a prospective trial involving 10,273 women with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer. Of the 9719 eligible patients with follow-up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease-free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS: Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease-free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease-free survival (83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local-regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease-free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS: Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who had a midrange 21-gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORx ClinicalTrials.gov number, NCT00310180 .).

Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.

BACKGROUND: Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. METHODS: We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). RESULTS: Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). CONCLUSIONS: Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

Influencia de los subtipos de cáncer de mama determinados por inmunohistoquímica en la recurrencia local y a distancia en pacientes sometidas a cirugía como tratamiento inicial / Influence of breast cancer subtypes determined by inmunohistochemestry in the local and distant recurrence in patients that underwent surgery as first treatment

Introducción: El cáncer de mama es una enfermedad heterogénea y es posible identificar, mediante técnicas simples, como la inmunohistoquímica, 4 subtipos con comportamiento biológico y clínico diferente. Nuestro objetivo fue evaluar la influencia de estos subtipos en las tasas de recurrencia local y a distancia Métodos: Se evaluó retrospectivamente 2047 pacientes con cáncer de mama unilateral tratadas primariamente con cirugía radical o conserva-dora. Los subtipos de cáncer de mama fueron categoriza-dos en luminal A (RE+ y/o RP+; HER2-), luminal B (RE+ y/o RP+; HER2+); HER2 (RE-, RP-; HER2+) y triple negativo (RE-; RP-; HER2-). Se evaluaron los patrones de recurrencia local y a distancia para cada subtipo y según las variables clinicopatológicas mediante la metodología de incidencias acumuladas. Adicionalmente evaluamos la influencia de cada variable en la sobrevida global (SG) mediante el método de Kaplan-Meier. Resultados: Los subtipos de cáncer de mama mostraron diferencias estadísticamente significativas en las tasas de incidencia a 5 años de recurrencia local (0,43%, luminal A; 1,94%, luminal B, 2,26%, triple negativo; 2,42%, HER2) y a distancia (12,41%, luminal A; 20,22%, luminal B; 20,36%, triple negativo, 31,72%, HER2). Ninguna variable clinicopatológica fue asociada con la recurrencia local, no obstante, se observó asociación de la recurrencia a distancia con la edad ≤40 años, compromiso ganglionar, extensión extracapsular y tamaño tumoral >2 cm. Debido a que hubo diferencias significativas en el tamaño tumoral entre las pacientes sometidas a cirugía con-servadora o radical, el tipo de cirugía no fue una variable evaluable. Conclusión: Los subtipos de triple negativo y HER2 mostraron mayor incidencia de recurrencia a nivel local o a distancia. El compromiso ganglionar, el tamaño del tumor mayor a 2 cm y la edad ≤40 años, fueron factores de riesgo asociados a la recurrencia a distancia.

Introduction: Breast cancer is a heterogeneous malignancy and it‘s possible to identify by simple techniques, such as immunohistochemistry, 4 subtypes with different clinical and biological behavior. Our aim was to evaluate the influence of these subtypes on the local and distant recurrences rates. Methods: We evaluated retrospectively 2047 unilateral breast cancer patients primarily treated with radical or conservative surgery. Breast cancer subtypes were categorized in luminal A (RE+ and/or RP+; HER2-), luminal B (RE+ and/or RP+; HER2+); HER2 (RE-, RP-; HER2+) and triple negative (RE-; RP-; HER2-). Patterns of recurrence for each subtype and clinicopathological variables were evaluated by the cumulative incidence methodology. In adition, we evaluated the influence of each variable on the overall survival (OS) by the Kaplan—Meier method. Results: Subtypes of breast cancer shown significant differences in 5-years incidence rates to local recurrence (0,43%, luminal A; 1,94%, luminal B, 2,26%, triple negative; 2,42%, HER2) or distant recurrence (12,41%, luminal A; 20,22%, luminal B; 20,36%, triple negative, 31,72%, HER2). None clinicopathological variable was associated with local recurrence; however, it was observed an association between the distant recurrence with an age ≤ 40 years old, nodal involvement and 2cm tumor size and the age ≤40 years were risk factors associated with distant recurrence.

Evaluación de factores pronósticos en pacientes con adenocarcinoma avanzado de vesícula biliar / Evaluation of prognostic factors in patients with advanced gallbladder adenocarcinoma

Introducción: Los cánceres de la vesícula biliar son poco frecuentes pero altamente letales y difíciles de detectar y tratar. El objetivo de este estudio fue evaluar variables que podrían influir en el pronóstico de los pacientes con adenocarcinoma avanzado de vesícula biliar. Métodos: Sesenta y cinco casos diagnosticados en el INEN con adenocarcinoma avanzado de vesícula biliar con confirmación patológica entre enero del 2001 y diciembre del 2008 fueron elegibles para este estudio. Resultados: La mediana de edad fue de 62 años. El 60% tenía ≥ 60 años, el 73,8% fueron mujeres, el 64,6% tenían estado de performance (EP) ECOG ≥ 2, 52,3% tuvieron estadio clínico (EC) III, los grados histológicos fueron 4,6%, 36,9% y 46,2% para los grados 1, 2 y 3 respectivamente, un paciente tuvo cirugía curativa, 16,9% tuvieron cirugía paliativa; 29,2% tuvieron cirugía incidental y el 52,3% no fue sometido a cirugía. La mediana de sobrevida global para todos los pacientes fue de 2,47 meses (m). Se observaron diferencias con respecto al estadio clínico (P <0,001 a favor del EC III), estado funcional (P <0,008 a favor del EP ECOG <2), quimioterapia (P = 0,04 a favor de quimioterapia), ictericia (P= 0,019, a favor de ausencia de ictericia) y sitio de metástasis (P<0,004 a favor de ausencia de metástasis). Conclusiones: La presencia de ictericia, metástasis a distancia, EP ECOG ≥2, EC IV y el uso de terapia de soporte son factores que podrían influir negativamente en la sobrevida de los pacientes con adenocarcinoma avanzado de vesícula biliar. Se necesita la realización de un estudio prospectivo aleatorizado para validar estos hallazgos.

Introduction: Gallbladder cancers are infrequent but lethal malignancies and difficult to detect and treat. The aim of our work was to evaluate variables that could influence the prognosis of patients with advanced gallbladder adenocarcinoma. Methods: Sixty five cases of advanced gallbladder cancer diagnosed by pathologic confirmation at INEN between January 2001 and December 2008 were eligible for this study. Results: Median age was 62 years. Sixty percent was ≥ 60 years old, 73.8% were female, 64.6% had ECOG ≥ 2, 52.3% had clinical stage III, 4.6%, 36.9% and 46.2% had histological grade 1, 2 and 3 respectively, only one patient underwent curative intent surgery, 16.9% had palliative surgery, 29.2% had incidental surgery and 52.3% had no surgery. Median overall survival was 2.47 months (mo). Statistically significant differences were observed with clinical stage (P = <0.001, favorable for EC III), status performance (P <0.008, favorable for PS ECOG < 2), chemotherapy (P = 0.04, favorable for chemotherapy), jaundice (P= 0.019, favorable for absence of jaundice) and site of metastases (P=<0.001, favorable for absence of metastases). Conclusions: Presence of jaundice, ECOG ≥ 2, CS IV, use of supportive therapy or presence of metastasis could have a negative impact in survival in patients with advanced gallbladder adenocarcinoma. A prospective randomized trial is necessary to validate this findings.

Características clínicas, patológicas y evolución en pacientes con cáncer de mama hereditario y esporádico en el Instituto Nacional de Enfermedades Neoplásicas / Clinical, pathological characteristics and evolution in patients with hereditary and sporadic breast cancer at the Instituto Nacional de Enfermedades Neoplasicas

Determinar las características clínicas, patológicas y evolución de pacientes con cáncer de mama hereditario y esporádico evaluados en un centro oncológico nacional. Material y métodos: Se realizó un estudio retrospectivo observacional en el Instituto Nacional de Enfermedades Neoplásicas (2009-2010) que evaluó las características clínicas, patológicas y sobrevida de 95 pacientes con cáncer de mama esporádico, y 59 casos con patrón hereditario diagnosticados en base a la historia familiar por el servicio de Genética. Resultados: La media de edad fue significativamente menor en los casos hereditarios que los esporádicos (53,5 vs. 44,8 años; p<0.001). Las pacientes con cáncer esporádico fueron diagnosticadas en estadios clínicos más avanzados debido a diferencias significativas en el tamaño tumoral. El fenotipo triple negativo fue más frecuente en los casos con patrón hereditario que los esporádicos (44.1 vs. 28.9%; p=0.036). La indicación de quimioterapia neoadyuvante fue significativamente mayor en el grupo esporádico. Las tasas de sobrevida libre de enfermedad y sobrevida global no alcanzaron significancia estadística. Conclusiones: Los casos de cáncer de mama hereditario presentan con mayor frecuencia fenotipo triple negativo y son diagnosticados a menor edad en promedio que los esporádicos. Las tasas de sobrevida global y sobrevida libre de enfermedad fueron similares entre ambos grupos.

Describe the clinicopathological characteristics and outcome in patients with hereditary and sporadic breast cancer selected from a national cancer center. Material and methods: We conducted a retrospective observational study at the Instituto Nacional de Enfermedades Neoplásicas (2009-2010), including 95 sporadic and 59 hereditary breast cancer patients. They were diagnosed on basis of their family history by the Department of Genetics. Results: The median age at diagnosis of hereditary cases were significant lower than sporadic (53,5 vs. 44,8 years; p=<0.001). Sporadic cancer patients were diagnosed at more advanced stage mainly because of an increased tumor size. Triple-negative cases were statistically more common in the hereditary than sporadic group (44.1 vs. 28.9%; p=0.036). Indication for neoadjuvant chemotherapy was more frecuent in sporadic cases. Overall survival and disease-free survival did not reach statistical significance. Conclusions: Hereditay breast cancer tumors preferentially show a triple negative phenotype and patients are diagnosed at younger age than sporadic cases. Overall survival and disease-free survival were both similar between the two groups.

Validación externa de un nomograma para predecir una subsecuente metástasis cerebral en pacientes con cáncer de mama metastásico / External validation of a nomogram to predict subsequent brain metastases in patient with metastatic breast cancer

Introducción: Graesslin et al. (JCO2002; 12:2032-37) desarrollaron un monograma para predecir una subsecuente metástasis cerebral en pacientes con cáncer de mama metastásico. Nuestro objetivo fue evaluar la capacidad predictiva de este monograma en nuestra población. Métodos: se incluyeron 327 pacientes con cáncer de mama unilateral sin metástasis cerebral como primer sitio de metástasis. Se calculó la probabilidad de recurrencia cerebral de cada paciente de acuerdo al monograma propuesto por Graesslin et al. La curva de la característica operativa del receptor (ROC) derivada del área bajo la curva (AUC) fue usada para cuantificar la capacidad predictiva del nomograma. Resultados: Con una mediana de seguimiento de 6.5 años, 51 pacientes desarrollaron metastásicos cerebral (15.6%). Con los 327 pacientes, construimos una curva ROC y el modelo predictivo tuvo una pobre discriminación con una AUC de 0.586 (IC 95%, 0.498 – 0.675). Conclusiones: El nomograma propuesto por Graesslin et al. Mostró una baja capacidad discriminativa para predecir una subsecuente metástasis cerebral en nuestros pacientes.

Introduction: Graesslin et al. (JCO2002; 12:2032-37) developed a nomogram to predict subsequent brain metastases in metastatic breast cancer. Our aim was evaluate the predictive ability of this nomogram in our population. Methods: We included 327 patients with unilateral breast cancer without brain metastases as first metastatic site. We calculated the probability of brain recurrence of each patient according to nomogram proposed by Graesslin et al. The receptor operation characteristic (ROC) curve derived from the area under the curve (AUC) was used to quantify the predictive capability of the nomogram. Results: With a median of follow up of 6.5 years, 51 patients developed brain metastases (15.6%). With the 327 patients, we constructed a ROC curve and the model had a poor discrimination with an AUC of 0.586 (CI95%, 0.498-0.675). Conclusions: The nomogram proposed by Graesslin et al. showed a low discriminative ability to predict a subsequent brain metastases in our patients.

Factores asociados con la respuesta patológica a la quimioterapia neoadyuvante en el cáncer triple negativo / Factors associated with pathologic response to neoadjuvant chemotherapy in triple negative cancer

Introducción: Los tumores de mama triple negativo (TN) representan aproximadamente entre el 20% al 25% de todos los cánceres de mama. El manejo clínico de estos tumores ha cambiado dramáticamente y se ha evaluado el rol de la neoadyuvancia. Nuestros objetivos fueron determinar las tasas de respuesta completa patológica (RCp) y su influencia en la sobrevida global (SG) y sobrevida libre de enfermedad (SLE). Métodos: Se realizó una revisión retrospectiva de 89 casos con tumores de mama TN diagnosticados y tratados con quimioterapia neodayuvante en el Instituto Nacional de Enfermedades Neoplásicas (Lima-Perú) durante el 2002-2007. Se evaluó la asociación entre las principales variables clinicopatológicas con la respuesta patológica y se calcularon las tasas de SLE, el tiempo a la progresión y la SG según el tipo de respuesta patológica. Resultados: La mediana de edad al diagnóstico fue de 40 años, 56 pacientes (62.95) solo recibieron quimioterapia en neoadyuvancia, 23 (25.8%) recibieron quimioterapia seguida de radioterapia y 10 (11.2%) quimioterapia y radioterapia concurrentes. Once paciente (17.7%) presentaron respuesta patológica completa. Los factores asociados con enfermedad residual fueron: grupo de edad <40 años (riesgo relativo [RR]=4.2; P=0.001), nulípara o un hijo (RR=4.5; P=0.042) y edad al primer embarazo mayor o igual a 30 años (RR=4.7; P=0.031). Con una mediana de seguimiento de 3.4 años, la SG fue de 87.3% al primer año fue y 51.8% en el tercer año. La SLE para las pacientes con RCp fue de 90.9% al tercer año y del 54.6% para pacientes con enfermedad residual (P=0.043); la SG al tercer año fue año 100% para pacientes con RCp, y del 54.6% para pacientes con enfermedad residual (P=0.035). Conclusiones: Se observaron las tasas de respuesta similares a algunos reportes publicados previamente y se encontraron algunas variables que estarían asociadas a la enfermedad residual. La RCp predijo altas tasas de SLE y SG.

Introduction: Triple negative (TN) breast tumors occur in approximately 20% to 25% of all breast cancers. The clinical management of these tumors has dramatically changed and the role of neoadjuvancy has been evaluated. Our aims were determine the pathologic complete response (pCR) rates and its influence in the overall survival (OS) and disease-free survival (DFS). Methods: We realized a retrospective review of 89 cases with TN breast tumors diagnosed and treated with neoadjuvant chemotherapy at the Instituto Nacional de Enfermedades Neoplasicas (Lima – Perú) in the period 2002 – 2007. Association between the main clinicopathologic variables and pathological response was evaluated; also was calculated the rates of DFS and OS according to type of pathological response. Results: The median age at diagnosis was 40 years, 56 patients (62.9% received only neoadjuvant chemotherapy, 23 (25.8%) received chemotherapy then radiotherapy and 10 (11.2%) received concurrent chemotherapy and radiotherapy. Eleven patients (17.7%) achieved pCR. Factors associated with residual disease were: <40 years age group (relative risk [RR]=4.2; P=0.001), nulliparous or 1 child (RR=4.5; P=0.042) and age to first pregnancy more than years (RR=4.7; P=0.031). With a median of follow-up of 3.4 years, OS for all patients was 87.3% at first year and 51.8 at third year. Three years-DFS for patients achieving pCR was 90.9% and 54.6% to patients with residual disease (P=0.043); 3-years OS was 100% for patients with pCR and 54.6% for patients with residual disease (P=0.035). Conclusions: We observe similar response rates to some reports published previously and we found some variables associated to residual disease, pCR predicted high rates of DFS and OS.

Sincronismo de un cáncer de mama temprano con un linfoma T del adulto / Synchronism of an early breast cancer with an adult T-cell lymphoma

La presentación secuencial de varias neoplasias primarias de un mismo individuo se ha descrito previamente; sin embargo, la presencia sincrónica de dos neoplasias de diferente estirpe histológica es poco frecuente. Presentamos un caso de sincronismo de un cáncer de mama metastásico y un linfoma T del adulto.

Concurrent presentation of several neoplasias in the same subject has been previously described; however, synchronous presentation of two neoplasias with distinct histological lineage in infrequent. We present a case with metastatic breast cancer and an adult T-cell lymphoma.

Patrones clínicos de los tumores de mama de acuerdo a su fenotipo en la población peruana / Clinical patterns of breast tumors according to their phenotype in the Peruvian population

Introducción: La clasificación de los tumores de mama estuvo basada en características histológicas, mientras que variables clinicopatológicos eran usadas como factores predictivos del curso clínico de la enfermedad. Los estudios de los perfiles genéticos consiguieron una clasificación molecular mucho más exacta. El objetivo de este estudio fue evaluar los patrones clínicos y de recurrencia de los tumores de mama de acuerdo a su fenotipo determinado por inmunohistoquímica. Material y métodos:Evaluamos un cohorte de 1044 pacientes diagnosticados con cáncer de mama operable entre los años 2000-2002 diagnosticados y tratados en el Instituto Nacional de Enfermedades Neoplásicas. Los fenotipos fueron caracterizado por inmunohistoquímica en [RE+ y/o RP+, HER2+], triple negativo [RE-, RP-, HER2-] y HER2+ [HER2+, sin importar el estado de los receptores hormonales]. Se evaluó la significancia pronóstica del fenotipo. Resultados: En nuestros casos, el 519 (49.7%) presentaron tumores [RE+ y/o RP+, HER2-], 212 (20.3%) presentaron tumores triple negativo y 313 (30.0%) presentaron tumores HER2+. El 23.2% (242) de los casos presentaron recurrencia local o a distancia y el 22.5% (235) fallecieron. El fenotipo [RE+ y/o RP+, HER2+] mostró una frecuencia más elevada de metástasis ósea (38.9%), seguido del fenotipo HER2 (27.2%) y triple negativo(23.6%). El fenotipo triple negativo mostró una baja tendencia a producir metástasis hepática (1.8%) comparado con [RE+ y/o RP+, HER2+] y HER2+ (21.1% y 19.6%, respectivamente). Se encontraron diferencias entre fenotipos en la sobrevida libre de enfermedad (P=0.001) y sobrevida global (P=0.005) los riesgos relativos de recurrencia y muerte fueron tiempo dependientes. Conclusiones: El fenotipo triple negativo y HER2+ se comportan como tumores altamente agresivos. La determinación del fenotipo por inmunohistoquímica es una excelente herramienta del pronóstico del curso de la enfermedad.

Introduction: The classification of breast tumors was based on histologic features, while clinicopa-thologic variables were used as predictors of clinical course of the disease. Studies of genetic profiles obtained a more accurate molecular classification. The objective of this study was to evaluate the clinical patterns and recurrence of breast tumors according to their phenotype determined by immunohistochemistry. Material and methods: We evaluated a cohort of 1044 patients diagnosed with operable breast cancer diagnosed between 2000-2002 and treated at the Instituto Nacional de Enfermedades Neo-plasicas. The phenotypes were characterized by immunohistochemistry in [ER + and / or PR +, HER2+], triple negative [ER-, PR-, HER2-] and HER2 + [HER2 +, regardless of the status of hormone recep-tors]. We assessed significant prognostic phenotype. Results: In our cases, 519 (49.7%) had tumors [ER + and / or PR +, HER2-], 212 (20.3%) had triple-negative tumors and 313 (30.0%) had HER2 + tumors. 23.2% (242) of cases had local or distant recurrence and 22.5% (235) died. The phenotype [ER + and / or PR +, HER2 +] showed a higher frequency of bone metastasis (38.9%), followed by HER2 phenotype (27.2%) and triple negative (23.6%). The triple negative phenotype showed a low tendency to produce liver metastases (1.8%) compared with [ER + and / or PR +, HER2 +] and HER2 + (21.1% and 19.6%, respectively). Differences were found between phenotypes in disease free survival (P = 0.001) and overall survival (P = 0.005) relative risks of recurrence and death were time dependent. Conclusions: Triple negative phenotype and HER2 + tumors behave as highly aggressive. The determination of the phenotype by immunohistochemistry is an excellent tool for predicting the course of the disease.

Compromiso leptomeníngeo en cáncer de mama: opciones terapéuticas actuales / Leptomeningeal involvement in breast cancer: current therapeutic options

El Cáncer de Mama sigue siendo una causa importante de muerte en mujeres en el mundo. En el Perú representa la segunda neoplasia más común en mujeres. El desarrollo de metástasis en el sistema nervioso central es una de las consecuencias más devastadoras de la progresión de la neoplasia. La carcinomatosis leptomeníngea ocurre en el 3.5% a 5% de los pacientes con Cánceres de Mama avanzado. Hay factores de riesgo para el desarrollo de la misma, como edad temprana al diagnóstico, metástasis pulmonar previa, Cáncer de Mama triple negativo, sobre expresión de HER-2, entre otros. El cuadro clínico generalmente es multifocal y debe ir acompañado del hallazgo de células neoplásicas en el líquido cefalorraquídeo, aunque esta tiene un nivel de sensibilidad bajo. Además se puede evidenciar hallazgos en resonancia magnética que nos orienten al diagnóstico. En los últimos 20 años las pacientes con Cáncer de Mama han experimentado un aumento en el tiempo de sobrevida, gracias al avance de los tratamientos sistémicos. Sin embargo, debido a esta causa existe un incremento en la incidencia de metástasis cerebrales, lo mismo que en la carcinomatosis leptomeníngea. Actualmente se tienen escasas opciones terapéuticas con poco impacto en el tiempo de sobrevida. El tratamiento se orienta más hacia buscar una adecuada calidad de vida. Aún faltan más estudios que respalden los buenos resultados de capecitabina, trastuzumab, lapatinib y ARA-C liposomal, encontrados en reportes aislados para definir un tratamiento estándar.

Breast cancer remains a major cause of death in women worldwide. In Peru it is second most common malignancy among women. The development of metastases in the central nervous system is one of the most devastating consequences of the progression of disease. Leptomeningeal carcinomatosis occurs in 3.5 to 5% of patients with advanced breast cancers, there are risk factors for developing it such as: early age at diagnosis, previous lung metastases, triple negative breast cancer, overexpression of HER -2, among others. The clinical picture is usually multifocal and mustbe accompanied by the presence of neoplastic cells in the cerebrospinal fluid, although this is anunusual finding. Magnetic resonance imaging findings can help in the diagnosis. In the past 20 years, breast cancer patients have experienced an increase in survival time, due to improvement insystemic treatments, however in relation to this there is an increasing incidence of brain metastases, and leptomeningeal carcinomatosis. Currently there are few treatment options with little impact onsurvival time, treatment being more oriented toward improving quality of life. We need more studies to support the success of capecitabine, trastuzumab, lapatinib and liposomal ARA-C are found inisolated reports to define a standard treatment.

Clasificación del cáncer de acuerdo a marcadores por inmunohistoquímica: distribución de subtipos y asociación con variables clínico patológicas / Classification according to cancer markers by immunohistochemistry: distribution of subtypes and association with clinicopathologic variables

Antecedentes: El cáncer de mama es la segunda neoplasia más común entre las mujeres en Perú. La clasificación molecular ha demostrado ser la mejor variable pronóstica y predictiva. El objetivo de este estudio fue evaluar las diferencias en las características clínico-patológicas y la sobrevida global en los cuatro subtipos moleculares de cáncer de mama: Luminal A (RE+ y/o RP+, HER2-); Luminal B (RE+ y/o RP+, HER2+); Tipo Basal (RE-, RP-,HER2-) Y Her2/neu (RE-,RP-,HER2+). Métodos: Se revisaron las historias clínicas de 1198 pacientes diagnosticados de cáncer de mama y tratados en el Instituto Nacional de Enfermedades Neoplásicas (Lima, Perú) entre el 2000 y 2002. La evaluación de RE, RP y HER2 se realizó por inmunohistoquímica, en tejidos fijados en formol e incluidos en parafina; la sobrevida global se calculó mediante el método de Kaplan-Meier. La prueba de log-rank se utilizó para determinar la significación estadística. Resultados: De 1198 canceres de mama invasivos, 591 (49.3%) fueron Luminal A, 158 (13.2%) Luminal B,255 (21.3%) Tipo Basal y 194 (16.2%) HER2/neu. La media de edad en el momento del diagnóstico fue 51.5 años para Luminal A,49.6 para Luminal B;49.5 para el Tipo Basal y el 49.4 para HER2/neu. El subtipo HER2/neu mostró un mayor porcentaje de; ganglios linfáticos positivos (63.7%), casos enestadio III (42.3%) y casos en estadio IV (9.7%). El subtipo Basal presentó una mayor prevalencia de fenotipo histológico pobremente diferenciado (70.3%). La mediana de seguimiento fue de 60 meses. La Sobrevida Global de 5 años mostró diferencias significativas entre los cuatro grupos (p <0.0001). Los Luminal A tiene la mayor Sobrevida Global, seguido de los Luminal B, Tipo Basal y HER2. Comparamos nuestros resultados con estudios de otras poblaciones y encontramos que las frecuencias relativas de los subtipos moleculares de nuestros pacientes son similares a las reportadas por la población de Carolina del Norte.

Background: Breast Cancer (BC) is the second most common neoplasm among women in Perú. The molecular classification has shown to be the best prognostic and predictive variable. The aim of this study was to evaluate differences in the clinicopathologic features and the overall survival (OS) in the four BC molecular subtypes: Luminal A (ER+ and/or PR+, HER2-); luminal B (ER+ and/or PR+, HER2+); Basal cell like (ER-,PR-, HER2-) and Her2/neu (ER-,PR-,HER2+) Methods: We reviewed the clinical records of 1198 BC patients diagnosed and treated at the Instituto Nacional de Enfermedades Neoplásicas (Lima, Peru) from 2000 to 2002. Evaluation of ER, PR and HER2 was performed by IHC in formalin-fixed, paraffin-embedded tumor samples; OS was calculated using the Kaplan-Meier method. The log-rank test was used to examine the statistical significance. Results: Of 1198 invasive Be, 591 (49.3%) were luminal A, 158 (13.2%) luminal B, 255 (21.3%) basal like and 194 (16.2%) Her2. The mean of age at diagnosis was 51.5 years for luminal A; 49.6 for luminal B;49.5 for Basal cel llike and 49.4 for Her2. Her2 subtype showed the highest percentage of positive lymph nodes (63.7%), stage III cases (42.3%) and stage IV cases (9.7%). Basal Cell Like cases showed the highest prevalence of poorly differentiated phenotype (70.3%). The median follow-up was 60 months. The 5-year OS was different between the four groups (p<0.0001). Luminal A had the highest OS followed by Luminal B, Basal Cell like and the HER2. We compared our results with other populations and we found that the relative frequencies of molecular subtypes of our patients are similar to that reported by the population of North Carolina, but different from Southern Switzerland (Ticino)and the Polish population. Conclusions: This study shows that there are significant differences between the distribution of molecular subtypes of breast cancer and clinicopathologic features.

Identificación de pacientes con cáncer de mama en riesgo de metástasis al sistema nervioso central / Identifying breast cancer patients at risk for central nervous system metastases

Introducción.- Se han propuesto que ciertas sub poblaciones de pacientes con cáncer de mama tendrían un riesgo incrementado de desarrollar metástasis en el sistema nervioso central (SNC). El objetivo de este trabajo es describir factores de riesgo para metástasis en el SNC en pacientes portadoras de cáncer de mama. Pacientes y Métodos.- Se realizó una revisión retrospectiva de 1081 casos de cáncer de mama diagnosticados y tratados en el Instituto Nacional de Enfermedades Neoplásicas (Lima, Perú) durante los años 2000 al 2002, en estadios clínicos I, II, III o IV al momento del diagnóstico. La determinación de los marcadores: receptor de estrógeno, progesterona y Her2 se realizó por inmunohistoquímica. Se evaluó la incidencia acumulada de metástasis cerebrales de acuerdo a cada variable clínica o patológica. Resultados.- Un total de 1025 pacientes fueron diagnosticados en los estadios I, II o III. Dentro de este grupo 304 (29.7%) pacientes tuvieron una diseminación de la enfermedad local, regional o a distancia. Se identificaron un total de 56 pacientes con estadio IV, de los cuales 11 (19.6%) tuvieron metástasis al SNC en algún momento hasta la fecha del último control, mientras que 4 (7.1%) pacientes tuvieron en el SNC al diagnóstico. Se encontró relación significativa en términos de incidencia acumulativa entre primera metástasis al SNC y estado nodal, receptor de estrógeno, receptor de progesterona, Her2, sub tipo molecular y estadío clínico (P<0.01 para todas las variables). Conclusiones.- A pesar de observarse factores de riesgo significativos para el desarrollo de metástasis en el SNC, no se pueden discriminar aquellos pacientes que presentan alto riesgo de metástasis en el SNC.

Introduction.- It has been proposed that certain sub populations of breast cancer patients have an increased risk to develop central nervous system (CNS) metastases. The aim of this study is to describe risk factors to develop CNS metastases in breast cancer patients. Patients and Methods.- A retrospective review of 1081 cases of breast cancer patients with clinical stages I, II, III and IV was performed. Determination of estrogen and progesterone receptors and Her2 markers was done by immunohistochemistry. The accumulative incidence of CNS metastases was evaluated according to each clinico pathologic variable. Results.- A total of 1025 patients were diagnosed with breast cancer in stages I, II, III. In this group 304 (29.7%) had local, regional or distant disease. 56 patients were diagnosed with stage IV, in this group 11 (19.6%) had CNS metastases at some point until the date of last follow up, while 4 (7.1%) of patients had CNS metastases at diagnosis. There were significant differences in terms of accumulative incidence between CNS metastases and nodal status, estrogen receptor, progesterone receptor, Her2, molecular subtype, and clinical stage (P<0.01 for each variable). Conclusions.- Despite the observation of significant risk factors for the development of CNS metastases, it is not possible to determine those patients with high risk to develop CNS metastases.

Enfermedad trofoblástica gestacional (ETG): experiencia en el Instituto Nacional de Enfermedades Neoplásicas 1980-2005 / Gestational trophoblastic disease (GTD): experience at the National Institute of Neoplastic Diseases 1980-2005

Objetivo.- Evaluar el comportamiento clínico y los resultados del tratamiento de la ETG en el INEN en el periodo comprendido entre los años 1980 y 2005. Material y métodos.- Estudio retrospectivo realizado en el INEN entre ene-1980 y dic-2005. Se revisaron 595 historias clínicas, recopilando información clínica, tratamientos administrados, toxicidades reportadas, tasa de respuestas y sobrevida global, para los cálculos estadísticos se utilizaron las pruebas de Kaplan-Meier. Resultados.- Entre ene-1980 a dic-2005, fueron admitidas en el INEN 595 pacientes con diagnóstico de ETG: Mola Hidatiforme 254 casos (42.7%), Coriocarcinoma 201 casos (33.8%) y Mola invasiva 41 casos (6.8%) no se reportaron casos de Tumor del sitio de inserción placentaria. Las localizaciones más frecuentes de metástasis fueron: pulmón: 67.3%, vagina: 17.9%, sistema nervioso central: 8.7%, e hígado: 5.1%. Se catalogó las pacientes de acuerdo al Sistema Score de FIGO: Bajo riesgo (score 1-6) 348 pacientes (58.5%) y Alto riesgo (score >6) 247 pacientes (41.5%). El tratamiento fue con monodroga 50.4% y con poliquimioterapia 49.6%. Pacientes de bajo riesgo que recibieron tratamiento con Metotrexate VO obtuvieron respuesta completa en 66.1% de los casos y 97% de sobrevida global a 20 años. Las pacientes de alto riesgo lograron respuesta completa con MAC: 32.5 %, MEC 36.8 %, EMA-CO 50%, BEP 25%. La población de alto riesgo se dividió en dos sub-grupos de acuerdo al score mayor de 12 y menor de 12, hallándose diferencias en la sobrevida global a 20 años de 80% para la población con score menor de 12 y 48% para el grupo con score mayor de 12 quienes presentaron metástasis en hígado y cerebro en 26.5%. Conclusiones.- ETG es una neoplasia altamente curable. Las pacientes de bajo riesgo que recibieron tratamiento con Metotrexate VO, lograron sobrevida global a 20 años de 97%. Existe diferencia en la sobrevida global entre pacientes de alto riesgo con score menor de 12 (80%).

Objective.-To evaluate the clinical behavior and results of treatment of gestational trophoblastic disease at the INEN between 1980 to 2005. Material and methods.- This is a retrospective analysis from January 1980 to December 2005. Evaluation included patient clinical characteristics, treatment, toxicity, response to therapies and survival. Descriptive statistics and Kaplan-Meier for survival analysis was also determined. Results.- 595 patients with GTD were evaluated from January 1980 to December 2005. Hydatidi form mole 254 (42.7%) choriocarcinoma 201 (33.8%) invasive mole 41 (6.8%), no cases with placental insertion trophoblastic tumor (PSTT) were seen. Sites of metastasis were: lung 67.3%, vagina 17.9%, brain 8.7%, liver 5.1%. Among these patients, 247 (41.5%) were categorized by FIGO scoring System as high risk (score >6) and 348 (58.5%) as low risk (score 1-6). The low risk patients whose received treatment with Metotrexate achieved complete remission in 66.1% of cases and the overall survival rate at 20 years was 97%. Patients with high risk who received treatment with: MAC, MEC, EMACO and BEP achieved complete remission in 32.5%, 36.8%, 50% and 25% respectively. High risk populations were divided in two groups according to score > 12 and 12, who developed liver and brain metastasis in 26.5%. The overall survival rate at 20 years, for those with score 12,48%. Conclusions.-Gestational trophoblastic disease is a highly curable neoplasia. Patients with low risk, who received Metotrexate, achieved 97% overall survival rate at 20 years. There are differences inoverall survival rate between patients of high risk those with score 12 (48%) the latter presented brain and liver metastasis. lt is important to define the best treatment for this group of patients.

Topoisomerasa II-alfa, como factor predictor de respuesta a la terapia con antraciclinas en cáncer de mama localmente avanzado / Topoisomerase II-alfa, as predictor of response to anthracycline therapy in locally advanced breast cancer

Introducción.- La enzima Topoisomerasa II-alfa es un blanco molecular de las antraciclinas; diversos estudios han sugerido que la expresión de esta enzima es un predictor de respuesta a la terapia con antraciclinas. El objetivo de este trabajo fue determinar si la sobre expresión de la Topoisomerasa II-alfa predice respuesta al tratamiento con antraciclínicas en pacientes con cáncer de mama localmente avanzado. Material y Métodos.- En este estudio se evaluó la expresión de la Topoisomerasa II-alfa, Her2, Receptorde Estrógeno y Receptor de Progesterona mediante inmunohistoquímica en tejidos de mama fijados en formol e incluidos en parafina de 111 tumores de pacientes con cáncer de mama localmente avanzado entre 1995 al 2002. El valor pronóstico de estos marcadores fue analizado. Resultados.- 40 (36%) casos mostraron sobre expresión de la Topoisomerasa II-alfa; el 62 (56%) para el Receptor de Estrógeno; para el Receptor de Progesterona 39 (35%) y 26 (23%) de expresión de Her2. No se observó diferencias significativas entre la expresión de Topoisomerasa II-alfa con respuesta a la terapia, con la sobrevida libre de progresión y sobrevida global. Cuando se comparó la sobrevida libre de enfermedad y sobrevida global con la densidad de dosis en casos que sobre expresaron la Topoisomerasa II-alfa, se observaron diferencias significativas (0.010 y 0.027). Conclusiones.- Aunque no se observó diferencias significativas en términos de sobrevida global, sobrevida libre de enfermedad o respuesta a la terapia; se describe que aquellos pacientes que sobre expresan la Topoisomerasa II-alfa presentan un mayor beneficio clínico cuando reciben una alta densidadde dosis de antracilinas.

Background.- Topoisomerase II-alfa is a molecular target for anthracyclines; several studies have suggested that expression of Topoisomerase II-alfa predicts is a predictor of response to treatment with anthracyclines. The aim of this study was to evaluate if the overexpression of Topoisomerase II-alfa predict response to treatment with anthracyclines in locally advanced breast cancer. Material and Methods.- This study evaluated the expression of Topoisomerase II-alfa, Her2, Estrogen Receptor and Progesterone Receptor by immunohistochemistry in formalin-fixed and paraffin embedded breast tumors in 111 tumors from patients with locally advanced breast cancer between the years 1995-2002. The prognostic value of these markers was analized. Results.- 40 (36%) samples showed over expression of Topoisomerase II-alfa 62 (56%) of Estrogen Receptor, 39 (35%) of Progesterone Receptor and 26 (23%) of Her2. There was no significant difference between the Topoisomerase II-alfa expression and response to therapy, overall survival and progression free survival. When the overall survival and the disease free survival was compared with the dose intensity in tases over expressing Topoisomerase II-alfa, significant difference were observed (P=0.010 y 0.027). Conclusions.- Although there was no significant differences observed in terms of overall survival, progression free survival or response to therapy, we describe that patients over expressing Topoisomerase II-alfa, present a better clinical benefit when they are treated with a higher dose intensity of anthracyclines.

Amifostina previene la toxicidad secundaria a la quimioterapia con shop, en pacientes ancianos con linfoma agresivo / Amifostine prevents toxicity secondary to chemotherapy shop in elderly patients with aggressive lymphoma

Objetivo: Determinar si amifostina puede efectivamente disminuir los efectos colaterales de la quimioterapia intensa en pacientes ancianos con linfoma maligno. nosotros realizamos un estudio rendomizado fase II B, comparando amifostina mas CHOP a dosis estándares versus CHOP. Pacientes y Métodos: Se incluyeron 34 pacientes (pts) mayores de 69 años, no tratados previamente, con linfoma maligno agresivo. Recibieron seis ciclos de A-Chop con amifostina 910 mg/m en día 1 más ciclofosfamida 750 mg/m, doxorubicina 50 mg/m vincristina 1.4 mg/m en dia 1 y prednisona 100 mg/día por 5 días, cada 3 semanas, versus 6 ciclos de CHOP solo. Resultados: 34 pts (18 A-CHOP versus 16 CHOP) fueron evaluables. Factores demográficos y pronósticos fueron similares entre ambos grupos. La tasa de respuesta fue 73,3 por ciento (RC 60 por ciento) para A-CHOP y 78.5 por ciento (RC 64 por ciento) para CHOP. En relación a tratamiento, fueron adminitrados 73/90 (81 por ciento) ciclos de A-CHOP y 69/84 (82 por ciento) de CHOP, la mediana de tratamiento fue 17,4 semanas con A-CHOP y 20.3 semanas con CHOP (p=0.05). Transfusión de glóbulos rojos fue necesario en 1/92 (1 por ciento) y 4/82 (5 por ciento) ciclos de A-CHOP y CHOP. Los ciclos de quimioterapia que requieron hospitalización fueron 4/92 (4 por ciento) y 11/82 (13 por ciento) con A-CHOP y CHOP (p=0.05). Episodios de neutropenia febril hubieron 3/92 con A-CHOP (3 por ciento) y 8/82 con (10 por ciento). Los días de hospitalización debido a toxicidad por quimioterapia fuern 21 para A-CHOP y 76 para CHOP. Conclusiones: Estos resultados muestran mejor tolerancia del régimen CHOP con amisfostina en pacientes mayores con linfoma.

Objective: To determine whether amifostine can effectively disminish the intensity of chemotherapy-related side effects, we conducted a randomized phase II-trial, comparing amifostine plus -dose CHOP (A-CHOP) versus CHOP, in elderly patients with agressive NHL. Patients and Methods: We included 34 previously untreated elderly (70 years)pts. The received 6 cycles of A-CHOP with amisfostine 910 mg / m on day 1 plus cyclophosphamide 750 mg / m², doxorubicin 50 mg / m vincristine 1.4 mg / m on day 1 and prednisone 100 mg / day for 5 days every 3 weeks, versus 6 cycles of CHOP alone. Results: 34 pts (18 A-CHOP CHOP versus 16) were evaluated. Demographic factors and prognosis were similar between both groups. The response rate was 73.3 per cent (60 per cent RC) for A-CHOP and 78.5 per cent (64 per cent RC) for CHOP. In relation to treatment were administrator 73/90 (81 per cent) cycles of A-CHOP and 69/84 (82 percent) of CHOP, the median was 17.4 weeks treatment with A-CHOP and 20.3 weeks with CHOP (p = 0.05). Red cell transfusion was necessary in 1 / 92 (1 per cent) and 4 / 82 (5 per cent) cycles of A-CHOP and CHOP. The cycles of chemotherapy were hospitalized 4 / 92 (4 per cent) and 11/82 (13 per cent) with A-CHOP and CHOP (p = 0.05). Had episodes of febrile neutropenia 3 / 92 with A-CHOP (3 per cent) and 8 / 82, (10 per cent). The days of hospitalization due to toxicity from chemotherapy fuern 21 for A-CHOP and 76 for CHOP. Conclusions: These results show better tolerance amisfostina CHOP regimen in elderly patients with lymphoma.