Therapeutic Drug Monitoring of Erlotinib in Non-Small Cell Lung Carcinoma: A Case Study.

ABSTRACT: We describe a clinical case of an 84-year-old man diagnosed with non-small cell lung carcinoma and epidermal growth factor receptor mutation, who was treated with erlotinib, with doses adjusted by therapeutic drug monitoring. This case involved a clearance fluctuation leading to over-therapeutic drug concentrations of erlotinib and toxicity. The intrapatient and interpatient variability of erlotinib, in addition to other factors such as age or variations in liver clearance, create situations that are challenging in clinical practice. During treatment, erlotinib serum concentrations were measured, and the dose was accordingly adjusted. The erlotinib dose required to reduce toxicity (rash grade III) and maintain effective plasma concentrations, as well as clinical and radiological responses, was 50% of the initial dose, underscoring the relevance of therapeutic drug monitoring for tyrosine kinase inhibitors in routine clinical practice.

Cancer Immunotherapy with Cytokine-Induced Killer Cells.

Cytokine-induced killer (CIK) cells form under certain stimulation conditions in cultures of peripheral blood mononuclear cells (PBMCs). They are a heterogeneous immune cell population and contain a high percentage of cells with a mixed T-NK phenotype (CD3+CD56+). The ready availability of a lymphocyte source, together with the high proliferative rate and potent anti-tumor activity of CIK cells, has allowed their use as immunotherapy in a wide variety of neoplasms. Cytotoxicity mediated by CD3+CD56+ T cells depends on the major histocompatibility antigen (MHC)-independent recognition of tumor cells and the activation of signaling pathways through the natural killer group 2 member D (NKG2D) cell-surface receptor. Clinical trials have demonstrated the feasibility and efficacy of CIK cell immunotherapy even in advanced stage cancer patients or those that have not responded to first-line treatment. This review summarizes biological and technical aspects of CIK cells, as well as past and current clinical trials and future trends in this form of immunotherapy.

A Patient With Metastatic Sarcoma was Successfully Treated With Radiolabeled Somatostatin Analogs.

We present a sarcoma patient with a tumor reduction of more than 50% in lung metastasis after 2 single courses of the investigational medical product Lutathera (Lu-DOTA0-Tyr3-octreotate). She was resistant to more than 6 lines of therapy including all the available active drugs in soft tissue sarcomas. The high expression of somatostatin receptors was shown by microarrays and Octreoscan. The overall duration of response exceeded 1 year.

Tratamiento regional del sarcoma y melanoma localmente avanzado de la extremidad mediante la perfusión aislada con tumor necrosis factor α y melfalan asociada a hipertermia / Tumor necrosis factor α and melfalan-based hyperthermic isolated limb perfusion in locally advanced extremity soft tissue sarcomas and melanomas

Introducción El objetivo del estudio fue evaluar el número de amputaciones evitables en pacientes con sarcomas y melanomas localmente avanzados de las extremidades mediante la perfusión aislada de la extremidad (PAE) con melfalán y tumor necrosis factor α (PAE-MT) en condiciones de hipertermia. Material y métodos Se revisó a todos los pacientes con sarcoma y melanoma localmente avanzados de la extremidad que fueron tratados en nuestro centro con PAE-MT durante el periodo comprendido entre noviembre de 2001 y febrero de 2010. Se evaluó el porcentaje de respuestas, las amputaciones evitadas, la toxicidad del tratamiento, las complicaciones, el intervalo libre de enfermedad y la supervivencia global. Resultados Treinta pacientes (19 mujeres y 11 varones), con una mediana de edad de 60 años (14-82), fueron tratados con esta técnica. Tras un seguimiento medio de 23 meses, el porcentaje de respuestas globales fue del 93,4% (completas, 46,7%; parciales 46,7%). La mediana de duración de la respuesta fue de 5 meses (0-62) y la mediana de supervivencia global de 13,5 meses (rango 1-62). Se evitó la amputación en el 86,7% de los casos. En la actualidad, once pacientes (5 sin enfermedad, 2 con enfermedad residual en tratamiento, 2 con progresión local y 2 con progresión sistémica) están vivos. Conclusión Mediante la PAE hemos logrado evitar la amputación de 26 miembros afectos de melanoma y sarcoma localmente avanzados. La PAE es factible y segura en un entorno multidisciplinar (AU)

Introduction The aim of the study is to evaluate the limb salvage rate achieved by treating locally advanced extremity sarcoma and melanoma by hyperthermic isolated limb perfusion with melphalan and (..) (AU)

[Tumor necrosis factor α and melfalan-based hyperthermic isolated limb perfusion in locally advanced extremity soft tissue sarcomas and melanomas]. / Tratamiento regional del sarcoma y melanoma localmente avanzado de la extremidad mediante la perfusión aislada con tumor necrosis factor α y melfalan asociada a hipertermia.

INTRODUCTION: The aim of the study is to evaluate the limb salvage rate achieved by treating locally advanced extremity sarcoma and melanoma by hyperthermic isolated limb perfusion with melphalan and TNF-α (ILP-MT). MATERIAL AND METHODS: A retrospective study was conducted on patients suffering from locally advanced soft tissue sarcoma and melanoma of the limb and treated by means of ILP-MT between November 2001 and February 2010. The response rate, toxicity, complications, disease free intervals, overall survival and limb salvage rate were evaluated. RESULTS: A total of 30 patients (19 females and 11 males) with a median age of 60 years (14-82) were treated by this technique. The overall response rate was 93.4% (complete, 46.7%; partial 46.7%); the mean follow-up was 23 months. The median duration of response was 5 months (0-62), The median overall survival was 13.5 months (range 1 - 62). Limb salvage rate was 86.7%. Eleven patients are currently alive (5 without disease, 2 with residual disease on treatment, 2 with local progression and 2 with systemic progression). CONCLUSION: With the use of ILP-MT we have avoided the amputation of 26 limbs affected by locally advanced sarcoma or melanoma. ILP-MT is feasible and safe in a multidisciplinary environment.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy in patients with peritoneal carcinomatosis of colonic origin: outcomes after 7 years' experience of a new centre for peritoneal surface malignancies.

INTRODUCTION: Peritoneal carcinomatosis is a relatively frequent situation in the natural history of colorectal cancer and is associated with a dismal prognosis. Promising results have been shown after radical cytoreduction followed by intraperitoneal chemohyperthermic perfusion. The aim our study was to assess the outcomes after treating patients with peritoneal carcinomatosis of colonic origin by means of cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) followed by early postoperative intraperitoneal chemotherapy (EPIC). METHODS: Tumour resection was performed in accordance with the guidelines for oncologic surgery. Selective peritonectomies and remnant nodule electroevaporation were performed with the aim of achieving a complete cytoreduction. Peritoneal perfusion was carried out according to the Coliseum technique at 0.5-1 L/min, and chemotherapy was administered at 42oC for 40-90 min. Mitomycin C 10-12.5 mg/m(2) or oxaliplatin 360 mg/m(2) was used. Postoperative intraperitoneally administered 5-fluorouracil (5-FU) (650 mg/m(2) per day) was given for 5 consecutive days. RESULTS: Twenty patients were treated from 2001 to 2008. The mean peritoneal cancer index was 11 (range 2-39). Fifteen patients had undergone complete cytoreductive surgery. The morbidity was 40%. There was one case of death due to bone marrow aplasia. Ten patients had recurrence; five of them underwent salvage surgery. Two patients were treated with a second HIPEC. Actuarial overall survival and progression-free survival were 36% and 30% at 5 years, respectively, with a median follow-up of 18 (range 8-28) months. CONCLUSIONS: Cytoreductive surgery combined with HIPEC is a feasible technique that might increase patient survival. It represents a potential cure for selected patients who have no other alternatives.

Controversial origin of Pseudomyxoma peritonei.

Pseudomyxoma peritonei describes the accumulation of mucinous material in the abdominal cavity. The main diagnostic problem appears when the primary site of origin could be appendix or ovary. In this paper describe clinicopathological features and biological markers that support appendiceal origin.