Capecitabine Plus Aromatase Inhibitor as First Line Therapy for Hormone Receptor Positive, HER2 Negative Metastatic Breast Cancer.

(1) Background: recent evidence suggests that long low-dose capecitabine regimens have a synergistic effect with endocrine therapy as aromatase inhibitors (AIs), and might increase overall survival for hormone-receptor-positive, HER2-negative, metastatic breast cancer compared to both treatments. We performed a retrospective study to confirm the efficacy and expand the safety data for capecitabine plus AI (a combination henceforth named XELIA) for this indication. (2) We conducted a single-center retrospective cohort study of 163 hormone receptor-positive metastatic breast cancer patients who received either the XELIA regimen, capecitabine, or an aromatase inhibitor (AI) as single agents in first-line treatment. The primary endpoint was progression-free survival, and the secondary endpoints were overall survival, best objective response, and toxicity incidence. (3) Results: the median progression-free survival for patients receiving XELIA, AI, and capecitabine was 29.37 months (20.91 to 37.84; 95% CI), 20.04 months (7.29 to 32.80; 95% CI) and 10.48 (8.69 to 12.28; 95% CI), respectively. The overall response rate was higher in the XELIA group (29.5%) than in the AI (14.3%) and capecitabine (9.1%) groups. However, the differences in overall survival were not statistically significant. Apart from hand-foot syndrome, there were no statistically significant differences in adverse events between the groups. (4) Conclusions: this retrospective study suggests that progression-free survival and overall response rates improved with the XELIA regimen compared to use of aromatase inhibitors and capecitabine alone. Combined use demonstrated an adequate safety profile and might represent an advantageous treatment in places where CDK 4/6 is not available. Larger studies and randomized clinical trials are required to confirm the effects shown in our study.

[Tobacco use and lung cancer]. / Tabaquismo y cáncer de pulmón.

Smoking is the main cause of lung cancer. It plays a role in the etiology, and depending on the intensity and duration, it also has an influence on histology, stage and therapeutic outcome. Therefore, it is never too late to stop smoking. Tobacco smoke is so toxic, that there is no safe smoking modality. Filters, light cigarettes, pipes, water pipes, etc. are prohibitively harmful. In addition, the electronic nicotine delivery systems, besides promoting addiction, cause acute respiratory and cardiovascular effects. In addition, even though long-term consequences are yet to be known, cell proliferation and tumor progression have been identified. Tobacco control efforts should look at all these new products as its main threat.

El tabaquismo es la principal causa de cáncer de pulmón. Participa en la etiología y, dependiendo de la intensidad y duración, influye en el tipo histológico, el estadio de la enfermedad y el efecto del tratamiento, por lo que nunca es tarde para dejar de fumar. La toxicidad del humo del tabaco es tan alta que no existe ninguna modalidad segura de tabaquismo. Los filtros, las diferentes variedades de cigarros light, los puros, pipas de agua, etc. son prohibitivamente dañinas. Inclusive los diferentes dispositivos electrónicos para la administración de nicotina, además de promocionar la adicción, tienen efectos respiratorios y cardiovasculares a corto plazo y, aunque aún es pronto para conocer sus consecuencias a largo plazo, se han identificado efectos en la proliferación celular y progresión tumoral. Por lo anterior, las campañas para el control del tabaquismo deben considerar estos productos como su principal amenaza.

[Lung-cancer screening program in Mexico]. / Detección temprana de cáncer de pulmón en México.

La detección temprana de cáncer pulmonar (CP) en población de alto riesgo tiene el potencial de diagnosticar la enfermedad en estadios tempranos y facilitar el tratamiento oportuno con el fin de disminuir la tasa de mortalidad. En México, como en otros países en vías de desarrollo, además del tabaquismo, la exposición al humo de leña se posiciona como uno de los principales factores de riesgo para desarrollar CP, lo cual no se ha considerado en estudios de tamizaje previamente publicados. Distintas interrogantes surgen en relación con quiénes son las personas que presentan un alto riesgo de desarrollar CP en América Latina, cuál es el costo-beneficio de poner en marcha un programa de detección oportuna de CP en México y cuáles son los obstáculos que los países de la región enfrentan para su implementación.

Lung cancer screening has the potential to be diagnosed at an early stage which increases the possibility of curative treatment in order to decrease the mortality rate. In Mexico, as in other developing nations, along with wood smoke exposure is one of the main risk factors for developing lung cancer, not considered in previously published screening trials. Different questions arise concerning the population at higher risk to develop lung cancer in Latin America, the cost-benefit of implementing a lung cancer screening program and the obstacles facing developing countries when implementing a detection program. To knowledge, there are no lung cancer screening trials in Mexico.

Detección temprana de cáncer de pulmón en México / Lung-cancer screening program in Mexico

Resumen: La detección temprana de cáncer pulmonar (CP) en población de alto riesgo tiene el potencial de diagnosticar la enfermedad en estadios tempranos y facilitar el tratamiento oportuno con el fin de disminuir la tasa de mortalidad. En México, como en otros países en vías de desarrollo, además del tabaquismo, la exposición al humo de leña se posiciona como uno de los principales factores de riesgo para desarrollar CP, lo cual no se ha considerado en estudios de tamizaje previamente publicados. Distintas interrogantes surgen en relación con quiénes son las personas que presentan un alto riesgo de desarrollar CP en América Latina, cuál es el costo-beneficio de poner en marcha un programa de detección oportuna de CP en México y cuáles son los obstáculos que los países de la región enfrentan para su implementación.

Abstract: Lung cancer screening has the potential to be diagnosed at an early stage which increases the possibility of curative treatment in order to decrease the mortality rate. In Mexico, as in other developing nations, along with wood smoke exposure is one of the main risk factors for developing lung cancer, not considered in previously published screening trials. Different questions arise concerning the population at higher risk to develop lung cancer in Latin America, the cost-benefit of implementing a lung cancer screening program and the obstacles facing developing countries when implementing a detection program. To knowledge, there are no lung cancer screening trials in Mexico.

Tabaquismo y cáncer de pulmón / Tobacco use and lung cancer

Resumen: El tabaquismo es la principal causa de cáncer de pulmón. Participa en la etiología y, dependiendo de la intensidad y duración, influye en el tipo histológico, el estadio de la enfermedad y el efecto del tratamiento, por lo que nunca es tarde para dejar de fumar. La toxicidad del humo del tabaco es tan alta que no existe ninguna modalidad segura de tabaquismo. Los filtros, las diferentes variedades de cigarros light, los puros, pipas de agua, etc. son prohibitivamente dañinas. Inclusive los diferentes dispositivos electrónicos para la administración de nicotina, además de promocionar la adicción, tienen efectos respiratorios y cardiovasculares a corto plazo y, aunque aún es pronto para conocer sus consecuencias a largo plazo, se han identificado efectos en la proliferación celular y progresión tumoral. Por lo anterior, las campañas para el control del tabaquismo deben considerar estos productos como su principal amenaza.

Abstract: Smoking is the main cause of lung cancer. It plays a role in the etiology, and depending on the intensity and duration, it also has an influence on histology, stage and therapeutic outcome. Therefore, it is never too late to stop smoking. Tobacco smoke is so toxic, that there is no safe smoking modality. Filters, light cigarettes, pipes, water pipes, etc. are prohibitively harmful. In addition, the electronic nicotine delivery systems, besides promoting addiction, cause acute respiratory and cardiovascular effects. In addition, even though long-term consequences are yet to be known, cell proliferation and tumor progression have been identified. Tobacco control efforts should look at all these new products as its main threat.

Medical care costs incurred by patients with smoking-related non-small cell lung cancer treated at the National Cancer Institute of Mexico.

BACKGROUND: Smoking is a public health problem in Mexico and worldwide; its economic impact on developing countries has not been well documented. The aim of this study was to assess the direct medical costs attributable to smoking incurred by lung cancer patients treated at the National Cancer Institute of Mexico (INCan). METHODS: The study was conducted at INCan in 2009. We carried out a cost of illness (COI) methodology, using data derived from an expert panel consensus and from medical chart review. A panel of experts developed a diagnostic-therapeutic guide that combined the hospital patient pathways and the infrastructure, human resources, technology, and services provided by the medical units at INCan. Cost estimates in Mexican pesos were adjusted by inflation and converted into US Dollars using the 2013 FIX exchange rate for foreign transactions (1 USD = 13.06 Mexican pesos). RESULTS: A 297 incident cases diagnosed with any type of lung cancer were analyzed. According to clinical stage, the costs per patient were 13,456; 35,648; 106,186; and 144,555 USD, for lung cancer stages I, II, III, and IV respectively. The weighted average annual cost/patient was and 139,801 USD and the average annual cost/patient that was attributable to smoking was 92,269 USD. This cost was independent of the clinical stage, with stage IV representing 96% of the annual cost. The total annual cost of smoking-related lung cancer at INCan was 19,969,781 USD. CONCLUSIONS: The medical care costs of lung cancer attributable to smoking represent a high cost both for INCan and the Mexican health sector. These costs could be reduced if all provisions established in the Framework Convention of Tobacco Control of the World Health Organization were implemented in Mexico.

Use of bevacizumab in metastatic colorectal cancer: report from the Mexican opinion and analysis forum on colorectal cancer treatment with bevacizumab (September 2009).

Colorectal cancer is one of the most common cancers worldwide, and although associated mortality rates in South American countries are generally among the lowest in the world, they are on the rise. The prognosis of patients diagnosed with metastatic colorectal cancer has improved markedly over the last 12 years, increasing from 5 months with best supportive care to almost 2 years with combination chemotherapy plus bevacizumab. New prognostic and predictive biomarkers have been identified to guide therapy. Prognostic markers indicate patient survival independent of therapy and include disease stage, mutational status, and carcinoembryonic antigen. More recently, predictive markers of treatment outcomes have been identified. The most studied are mutations of the KRAS and BRAF genes, which are associated with resistance to epidermal growth factor receptor-targeted therapy. Tumor blood vessels have a number of structural and functional abnormalities that result in increased tumor vascularity and growth driven by angiogenesis. The anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab, which binds to and neutralizes VEGF-A, has become a central part of the treatment of metastatic colorectal cancer. The addition of bevacizumab to fluorouracil (5-FU)/leucovorin, irinotecan plus bolus 5-FU/leucovorin, or irinotecan plus infusional 5-FU/leucovorin significantly improves the overall survival of patients with previously untreated metastatic colorectal cancer. In addition, a significant increase in overall survival is seen when bevacizumab is added to oxaliplatin plus infusional 5-FU/leucovorin (FOLFOX) in patients with metastatic colorectal cancer who progressed on a non-bevacizumab-containing regimen. Although the majority of studies were performed prior to the identification of KRAS and BRAF as predictive biomarkers, subsequent analysis has shown the benefits of bevacizumab occur independently of the mutational status of these genes. In patients who have progressed on a bevacizumab-containing regimen, continuation of bevacizumab is significantly associated with an improved survival based on observational cohort studies. Surgical resection is recommended in patients with metastatic colorectal cancer where complete removal of tumors can be achieved. Perioperative chemotherapy using FOLFOX for 3 months before and 3 months after surgery is associated with a 9% improvement in 3-year survival. The use of chemotherapy in patients initially deemed unresectable has produced resection rates approaching 40%, and the addition of bevacizumab to chemotherapy in this setting is feasible, safe, and effective. In a study of 219 patients, the addition of bevacizumab to FOLFOX was associated with a significant increase in major or complete pathologic response compared with FOLFOX alone. Improvements in patient survival have changed the treatment paradigm for metastatic colorectal cancer. Newer approaches view treatment not as distinct lines of therapy but as a continuum that includes personalized treatment plans offering maintenance therapy and even drug holidays between aggressive treatment periods. This approach achieves similar efficacy outcomes with reduced toxicity, and investigation of the role of bevacizumab as maintenance therapy is ongoing.

Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer.

BACKGROUND: Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC. METHODS: One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 (FAC), or doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60 Gy breast irradiation and weekly mitomycin 5 mg/m2, 5-fluorouracil 500 mg/m2, and dexamethasone 16 mg, or cisplatin 30 mg/m2, gemcitabine 100 mg/m2 and dexamethasone 16 mg), and 6-8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90 mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy. RESULTS: Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2-50.5%) and, 29.5% (95% CI, 21.4-37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR=3.8; 95% CI, 1.5-9; p=0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2-84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR=3.1; 95% CI, 1.02-9.74; p=0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75-93.2%). The toxicity profile was acceptable. CONCLUSION: This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

Delayed administration of G-CSF until day +7 after autologous peripheral blood stem cell transplant is as effective in accelerating hematopoietic as day 0.

PURPOSE: To compare the hematopoietic recovery and the clinical outcome after high dose chemotherapy and peripheral blood stem cell (PBSC) transplant between patients who received recombinant granulocyte colony-stimulating factor (G-CSF) starting on day 0 and those who received it starting on day +7. PATIENTS AND METHODS: Thirty-five consecutive patients received high dose chemotherapy with ifosfamide, etoposide and carboplatin (ICE) and autologous PBSC transplant. PBSC mobilization was achieved with G-CSF. In 19 transplants done in 1994, G-CSF was started on day 0 and in 16 procedures done in 1995, G-CSF was started on day +7. In both groups G-CSF was given until the absolute neutrophil count was 1 x 10(9)/L. RESULTS: The median number of days to reach an absolute neutrophil count > 0.1 x 10(9)/L, was 11 in the patients who started the G-CSF on day 0 and 11 days in the patients with delayed administration of G-CSF and to reach > 0.5 x 10(9)/L 14 days and 13 respectively. The median number of days to reach a platelet count > 20 x 10(9)/L was 14 and 13. Comparison of early vs. delayed administration of G-CSF did not show any significant differences regarding the time to achieve platelet independence, number of days with fever, median days of hospital stay, number of red cell or platelet transfusions. CONCLUSIONS: Starting G-CSF on day +7 after high dose ICE chemotherapy and autologous transplant of PBSC is as effective in restoring the hematopoietic function as is starting its administration on day 0.

Bioavailability of etoposide after oral administration of the solution marketed for intravenous use: Therapeutic and pharmacoeconomic perspectives

Background. Oral etoposide administration is a suitable alternative to the intravenous route; therefore, commercial capsules have been developed. Before these capsules were available in Mexico, we studied drug bioavailability after oral administration of the intravenous etoposide solution (IVES). Methods. Eight adult cancer patients received a 50-mg oral etoposide dose as IVES and blood samples were collected over a period of 24 h. plasma etoposide concentration was determined by high-performance liquid chromatography, plasma concentration against time curves were constructed, and biovailability parameters were calculated. Results. Oral IVES yielded an adequate bioavailability profile because Cmax was 2.38 ñ 0.30 µg/mL, AUC was 12.87 ñ 2.02 µg/mL and half-life was 6.72 ñ 0.97 h. Conclusions. Considering that the pharmacokinetic aim is to maintain plasm concentrations between 0.5 and 1.0 µg/mL for several hours while avioding high concentrations, i.e., of 10 µg/mL or higher, oral administration of 50-mg etoposide as IVES appears to be a suitable dosing option. In addition, oral IVES is considerably less expensive than intravenous administration in terms of both drug presentation and administration

Quimioterapia neoadyuvante en cáncer de mama estadio clínico II-A y II-B / Neoadjuvant chemotherapy in breast cancer in clinical stages II-A and II-B

El uso de la quimioterapia en el manejo del cáncer de mama ocupa un papel muy importante en la actualidad. Su empleo en forma neoadyuvante se ha utilizado en etapa clínica II con el fin de poder llevar a cabo una cirugía conservadora mediante la reducción tumoral. El objetivo del presente trabajo fue evaluar la respuesta de la quimioterapia neoadyuvante en un grupo de enfermas con cáncer de mama en etapa clínica II, tanto a nivel del tumor primario como nivel ganglionar. Se evaluaron pacientes en etapa clínica II que recibieron quimioterapia neoadyuvante de mayo de 1989 a diciembre de 1995. Fueron incluidas 202 mujeres a quienes se les administró de dos a cuatro ciclos de tratamiento previos a cirugía. De éstas, 59 (29 por ciento) tenían etapa II-A y 143 (71 por ciento) II-B; la media de edad fue de 46.5 años (22-80). Se aplicaron tres esquemas diferentes, a 144 pacientes 5-fluoracilo adriamicina y ciclofosfamida, a otras 29 mujeres ciclofosfamida 5-fluoracilo y metotrexato y, finalmente, a 29 enfermas un esquema de cisplatino, ciclofosfamida y adriamicina. Las pacientes fueron distribuidas en dos grupos. El grupo A incluyó 142 mujeres a las que se evaluó la respuesta de acuerdo al tamaño del tumor primario y al número de ganglios positivos en la axila. El grupo B lo conformaron 60 enfermeras a las que, por manejo previo, sólo se les valoró la respuesta en la axila. En el grupo A, se redujo el estadio clínico en 83 (59 por ciento) casos, se alcanzó respuesta patológica completa en 30 (21 por ciento) y se registraron menos de cuatro ganglios positivos en axila en 100 (78 por ciento). Esto último se observó en 44 (73 por ciento) pacientes del grupo B. La supervivencia global a siete años fue de 70 por ciento. Con base en lo observamos en este estudio, concluimos que la quimioterapia neoadyuvante es efectiva para reducir el tamaño tumoral

Quimioterapia neoadyuvante en el carcinoma epidermoide de cabeza y cuello. Experiencia en el Instituto Nacional de Cancerología / Neoadyuvant chemotherapy in squamous cell carcinoma of head and neck. Experience in the Instituto Nacional de Cancerologia

Con el objeto de identificar factores pronósticos de respuesta clínica completa en carcinoma epidermoide de cabeza y cuello localmente avanzado, se analziaron retrospectivamente los registros de 72 pacientess tratados en el periodo comprendido de enero de 1986 a diciembre de 1994 con quimioterapia neoadyuvante, utilizando el esquema de 5 FU-cisplatino. Se observó que en los pacientes con cuello clínicamente negativo a metástasis ganglionares y con tumores bien diferenciados fue posible obtener un mayor índice de respuestas clínicas mayores al 50 por ciento después del primer ciclo de quimioterapia. Los pacientes que respondieron a la quimioterapia neoadyuvante también tuvieron mejor respuesta a radioterapia. Concluimos que aquellos pacientes con respuesta parcial después del primer ciclo de quimioterapia deben completar tres ciclos de quimioterapia, ya que esto incrementa los porcentajes de casos con respuesta completa, hecho que mejoran la supervivencia y aumenta la probabilidad de conservar el órgano en donde se origina el tumor, conclusión no validada previamente. Por el contrario, en los casos con porcentajes menores de respuesta posterior al primer ciclo, deberán ser aplicados a otros esquemas de tratamiento con el objeto de ofrecer mejores resultados de los ya conocidos

Tratamiento de cáncer pulmonar / Treatment of lung cancer

Se realizó un estudio prospectivo de pacientes diagnosticados con cáncer primario de pulmón, que ingresaron en el Instituto Nacional de Enfermedades Respiratorias de 1984 a 1992. Se estudió a 1,019 pacientes con cáncer primario de pulmón, y en ellos se valoraron los aspectos epidemiológicos y clínicos para obtener el diagnóstico, utilizando todos los recursos de estudio. Clasificamos el grado de avance del cáncer en cada enfermo. Encontramos que la gran mayoría presentaban estados avanzados de la enfermedad. Para recibir tratamiento quirúrgico, fueron seleccionados y clasificados en estadios I, II ó IIIA. Fue un grupo pequeño en el que fue posible practicar lobectomía o neumonectomía; los resultados inmediatos fueron buenos, pero desconocemos su evolución a mediano plazo. Un grupo importante de pacientes fue tratado con diferentes esquemas de radioterapia, quimioterapia o ambos; en este grupo, los resultados obtenidos fueron poco satisfactorios, pues la mayoría falleció en corto tiempo sin haber obtenido, con el tratamiento, mejorías importantes del cáncer pulmonar. Por lo anterior, consideramos que, en la actualidad, el cáncer primario de pulmón es un padecimiento grave y, cuando se manifiesta clínicamente, es mortal a corto plazo con o sin tratamiento. Para mejorar el pronóstico, es necesario incrementar las campañas de educación y orientación en la población adulta que tenga o no antecedentes de tabaquismo

Aspectos clínicos y radiográficos del cáncer pulmonar / Clinical and radiological features of bronchogenic cancer

Se relatan los resultados clínicos y radiográficos obtenidos en un estudio prospectivo efectuado a enfermos con carcinoma broncogénico comprobado histológicamente, internados en el Instituto Nacional de Enfermedades Respiratorias (INER) de 1984 a 1992. El estudio fue realizado por un grupo interdisciplinario de médicos del INER y del Instituto Nacional de Cancerología (INCan). Se confirmó la relación que existe entre el cáncer pulmonar y el tabaquismo. Se muestran los síntomas y signos que orientan al médico en el diagnóstico de tumor maligno pulmonar. La radiografía posteroanterior de tórax fue de vital importancia en la detección temprana en sujetos asintomáticos. En los casos avanzados, las imágenes radiográficas se pueden confundir con otras patologías pulmonares. No fue posible hacer una correlación precisa entre el tipo de cáncer y el cuadro clínico radiográfico; sin embargo, se describen algunas posibilidades