Mariano Provencio Pulla

Prevalencia de infección por el virus de la hepatitis C en pacientes con linfomas no hodgkinianos

Fundamento Conocer la prevalencia de la infeccion por el virus de la hepatitis C (VHC) en pacientes con linfoma no hodgkiniano(LNH-B) Pacientes y metodo Estudio transversal de pacientes con LNH-B, comparando serologia y ARN del VHC, datos analiticos, toxicidady respuesta al tratamiento Resultados El 66% presentabanelevacion de las transaminasas frenteal 10,3% en los pacientes negativos para el VHC. Conclusiones La prevalencia del VHC esmas alta en pacientes con LNH-B que en lapoblacion normal. El VHC podria tener unpapel en la etiopatogenia de estos linfomas

Old and New Insights in the Treatment of Thyroid Carcinoma

Thyroid cancer is the endocrine tumor that bears the highest incidence with 33 550 new cases per year. It bears an excellent prognosis with a mortality of 1530 patients per year (Jemal et al.; 2007). We have been treating patients with thyroid carcinoma during many years without many innovations. Recently, we have assisted to the development of new agents for the treatment of this disease with unexpected good results. Here we present a review with the old and new methods for the treatment of this disease.Thyroid cancer is the endocrine tumor that bears the highest incidence with 33 550 new cases per year. It bears an excellent prognosis with a mortality of 1530 patients per year (Jemal et al.; 2007). We have been treating patients with thyroid carcinoma during many years without many innovations. Recently, we have assisted to the development of new agents for the treatment of this disease with unexpected good results. Here we present a review with the old and new methods for the treatment of this disease.

Management of platinum-resistant ovarian cancer with the combination of pemetrexed and gemcitabine.

IntroductionPlatinum resistant ovarian cancer is a current challenge in Oncology. Current approved therapies offer no more of a 20% of response. New therapeutic options are urgently needed.Patients and MethodsPatients were treated with the combination of Pemetrexed 500 mg/m2 d1 and Gemcitabine 1000 mg/m2 d1, 8 in a 21 days basis.Results10 platinum-resistant ovarian cancer patients were treated under compassionate use. Mean previous chemotherapy lines were 3.3. Mean administered cycles were 4. Mean CA 125 decrease was on average of 47%, with one patient experiencing a 95% decrease in her CA 125 level. 1 patient had a complete clinical remission, and 2, had partial radiological responses. Mean Progression free survival was 16.5 weeks, and Overall Survival was 21.2 weeks. Treatment was well tolerated.ConclusionsDeemd to the observed activity, the combination of Pemetrexed and Gemcitabine deserves deeper investigation in platinum-resistant ovarian cancer patients.

Melanoma: from darkness to promise.

Metastatic melanoma is one of the most resistant tumors to standard chemotherapy approaches. The median overall survival of patients diagnosed with metastatic melanoma is lower than 9 months. Current approved treatments offer only marginal survival advantages. New immunotherapeutic targets have appeared recently trying to modulate the host immune response against the tumor. New targeted agents have changed the standard of care of other solid tumor types like breast cancer. Here, we discuss the new advances and achievements in the treatment of this highly resistant disease.Metastatic melanoma is one of the most resistant tumors to standard chemotherapy approaches. The median overall survival of patients diagnosed with metastatic melanoma is lower than 9 months. Current approved treatments offer only marginal survival advantages. New immunotherapeutic targets have appeared recently trying to modulate the host immune response against the tumor. New targeted agents have changed the standard of care of other solid tumor types like breast cancer. Here, we discuss the new advances and achievements in the treatment of this highly resistant disease.

Durable Complete Remission of a Brainstem Glioma Treated with a Combination of Bevacizumab and Cetuximab

Treatment of a relapsed glioma is a clinical challenge nowadays. New active treatments are required to treat these difficult diseases. Here we present a durable complete remission of a relapsed glioblastoma that has achieved a complete radiologic response with the combination of cetuximab and bevacizumab, in a third-line setting, that has offered a progression-free survival of 20 months. We consider here both potential mechanisms for the explanation of this result. First, the potential target of the cancer stem cells (CSCs) with these two antibodies, and second, the potential recruitment of the immune system to directly pursue the CSCs.

Role of consolidation with yttrium-90 ibritumomab tiuxetan in patients with advanced-stage follicular lymphoma

Non-Hodgkins lymphoma (NHL) accounts for 4% of all cancers diagnosed in the United States. Follicular lymphoma (FL) is the most common type of indolent NHL with a survival from 5 to 15 years. Although it is very sensitive to chemotherapy and radiotherapy, relapses are the main cause of therapeutic failure, and currently there is no consensus on the first-line treatment and optimal therapeutic strategies for patients with FL. Immediate treatment offers any survival benefit for asymptomatic and more indolent disease. In order to improve outcomes in FL, extend the remission, postpone the need for chemotherapy and improve OS, maintenance therapies with rituximab and consolidation treatments represent very attractive strategies. (90)Y-ibritumomab tiuxetan ((90)Y-IT, Zevalin®) is approval as consolidation therapy in previously untreated FL patients who achieve response to first-line chemotherapy. Consolidation therapy with (90)Y-IT after initial induction treatment has shown improved activity compared with induction chemotherapy alone, even in patients previously treated with rituximab, in one phase III and several phase II trials, improving progression-free survival (PFS) and rate of conversion from partial response (PR) to complete response (CR). The phase III international FIT trial shows an improvement in PFS that is maintained after a median follow up of 7.3 years. Several phase II trials show high rate of conversion from PR to CR and a significant improvement in PFS. Treatment is feasible and well tolerated although myelodysplastic syndrome cases has been observed in some trials. (90)Y-IT should be considered for the initial treatment of FL in patients who are unable to tolerate standard chemotherapy, e.g., elderly or frail patients and otherwise in high-risk patients who achieve a PR or CR due to improvements in CR rate and PFS.Non-Hodgkin’s lymphoma (NHL) accounts for 4% of all cancers diagnosed in the United States. Follicular lymphoma (FL) is the most common type of indolent NHL with a survival from 5 to 15 years. Although it is very sensitive to chemotherapy and radiotherapy, relapses are the main cause of therapeutic failure, and currently there is no consensus on the first-line treatment and optimal therapeutic strategies for patients with FL. Immediate treatment offers any survival benefit for asymptomatic and more indolent disease. In order to improve outcomes in FL, extend the remission, postpone the need for chemotherapy and improve OS, maintenance therapies with rituximab and consolidation treatments represent very attractive strategies. 90Y-ibritumomab tiuxetan (90Y-IT, Zevalin®) is approval as consolidation therapy in previously untreated FL patients who achieve response to first-line chemotherapy. Consolidation therapy with 90Y-IT after initial induction treatment has shown improved activity compared with induction chemotherapy alone, even in patients previously treated with rituximab, in one phase III and several phase II trials, improving progression-free survival (PFS) and rate of conversion from partial response (PR) to complete response (CR). The phase III international FIT trial shows an improvement in PFS that is maintained after a median follow up of 7.3 years. Several phase II trials show high rate of conversion from PR to CR and a significant improvement in PFS. Treatment is feasible and well tolerated although myelodysplastic syndrome cases has been observed in some trials. 90Y-IT should be considered for the initial treatment of FL in patients who are unable to tolerate standard chemotherapy, e.g., elderly or frail patients and otherwise in high-risk patients who achieve a PR or CR due to improvements in CR rate and PFS.

High-dose chemotherapy followed by autologous and allogeneic hematopoietic stem cell transplantation in patients with follicular non-Hodgkin’s lymphoma in the rituximab era.

High-dose chemotherapy in lymphomas, and mainly non-Hodgkins lymphomas, has been advancing since the 1970s. This therapeutic strategy is based on the supposed existence of a dose-response curve for cytotoxic agents. However, the available data are contradictory, so high-dose chemotherapy cannot be guaranteed as consolidation treatment for first-remission follicular lymphoma or diffuse large cell lymphoma. The objective of this paper is to review the current knowledge about high-dose chemotherapy followed by hematopoietic stem cell transplantation in follicular non-Hodgkins lymphoma. The published studies on follicular lymphoma after first remission, recurrent follicular lymphoma, and transformed follicular lymphoma were assessed together with the data available on diffuse large cell lymphoma. During analysis of the studies, difficulties were encountered in comparing studies due to the heterogeneous nature of the data. High-dose chemotherapy as consolidation treatment after first remission or in recurrent or refractory disease was also analyzed.

SEOM clinical guidelines for the treatment of diffuse large B-cell lymphoma.

Diffuse large B-cell non-Hodgkin’s lymphoma (LDCGB) is one of the best examples of chemotherapy curable malignant diseases. This “Oncoguía SEOM” summarizes the basic directions of staging and recommended treatment options. The staging study should be thorough and includes clinical, laboratory, diagnostic imaging and nuclear medicine. Treatment depends on patient characteristics and comorbidity and on disease extension and prognostic factors. In localized cases, chemoimmunotherapy (CHOP-R) of short duration, followed by involved-field irradiation is the preferred option. In advanced stages, the association of CHOP-like chemotherapy and Rituximab has been a major breakthrough in terms of cure rate. It is important do not forget the supportive treatment in these patients.

Breast cancer: contribution of molecular biology to the management of the disease

The possible applications of molecular biology to cancer research obviously surpass the confines of exclusively scientific knowledge, making available solid tools for the management of the disease. Breast cancer patients can be considered one of the populations that has most benefited from current research, both clinical and basic, probably as a consequence of the clinical epidemiological relevance of this malignancy. The applications of the knowledge contributed by molecular biology to the study of breast cancer can be grouped according to their mechanisms and the aspect of the disease for which they have been designed: as information complementary to pathologic diagnosis, as prognostic markers of the disease, as possible predictors of treatment response, as a rational basis for developing new treatment strategies, and as the molecular basis for establishing groups of hereditary cancers.ResumenLas posibilidades que en la actualidad ofrece la biología molecular, aplicadas al estudio del cáncer, sobrepasa claramente el límite de los conocimientos puramente científicos para ofrecer aplicaciones concretas en el control de la enfermedad. E1 cáncer de mama se puede considerar como uno de los más beneficiados por la investigación actual, tanto clínica como básica, quizá derivado de la importancia clínicoepidemiológica de esta neoplasia. Las aplicaciones de los conocimientos aportados por la biología molecular en cáncer de mama se pueden agrupar en varios contextos diferentes de la enfermedad dependiendo de su actuación: como ayuda complementaria al diagnóstico histológico, como marcadores del pronóstico de la enfermedad, pueden ser empleados como posibles predictores de la respuesta al tratamiento, como base racional para el desarrollo de estrategias de tratamiento y como la base analítica para establecer grupos de cánceres hereditarios.

Neoadjuvant use of Tyrosine Kinase Inhibitors

Patients with clinical stage IIIA-N2 non-small cell lung cancer (NSCLC) have a 5-year overall survival (OS) of only 10%-15%, and it decreases to 2-5% in patients with mediastina N2 bulky disease. The efficacy of surgery in this stage is limited and remains controversial. In 4 different studies with a total of 1180 patients who underwent surgical resection, 5-year survival was 14-30% [1-4]. To improve this rate and supported by the introduction of new chemotherapeutic agents, induction chemotherapy (CT) has been added to the treatment approach in this stage. The theoretical advantages of induction CT include: in vivo assessment of response to CT, which would help identify patients who might benefit from adjuvant CT; early treatment of micro metastasis to increase control of distant metastases; reduction of drug resistance due to early exposure to chemotherapeutic agents and increased surgical resect ability, due to enhance of response rates that also allows preservation of healthy lung parenchyma.