Toxicidad asociada a la cirugía citorreductora y quimioterapia intraperitoneal hipertérmica en el tratamiento de la carcinomatosis peritoneal / Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy associated toxicity in treatment of peritoneal carcinomatosis

Introducción La carcinomatosis peritoneal es una forma de diseminación intraabdominal de diversos tumores, asociada con mal pronóstico. La realización de cirugia citorreductora y administración de quimioterapia intraperitoneal hipertérmica constituye una alternativa para su tratamiento. El objetivo del estudio es describir la toxicidad derivada del procedimiento en pacientes diagnosticados de carcinomatosis peritoneal. Métodos Estudio descriptivo, retrospectivo, unicéntrico, incluyendo todos los pacientes sometidos al procedimiento, entre diciembre de 2007 y enero de 2010. Se registraron: datos antropométricos, antecedentes personales y quirúrgicos, indicación, tratamientos previos, grado de carcinomatosis, duración de la intervención, estancia hospitalaria, así como el tipo de complicaciones y/o eventos adversos tras la aplicación del tratamiento multidisciplinario. Resultados: Se realizaron 46 intervenciones en 45 pacientes diagnosticados de carcinomatosis peritoneal de diferentes etiologías, mayoritariamente cáncer de ovario (83%). El fármaco más utilizado fue paclitaxel (35 intervenciones). No hubo mortalidad asociada, el tiempo medio de intervención fue 6,4h y la estancia media hospitalaria 7 días. Se registraron eventos adversos en 42 procedimientos, siendo de grado 3-4 en un 28,3% de los pacientes. Las incidencias de reacciones severas fueron: 10,9% gastrointestinales, 10,9% (..) (AU)

Introduction Peritoneal carcinomatosis is a form of intra-abdominal dissemination of several tumours, which is associated with a poor prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is an alternative treatment. The aim of this study is to describe the toxicity associated with this procedure in patients with peritoneal carcinomatosis. Method We conducted a descriptive, retrospective, single-centre study, including all patients undergoing this procedure between December 2007 and January 2010. The following data were recorded: anthropometric data, personal and surgical events, indication, previous treatments, extent of carcinomatosis, intervention duration, hospital stay, and type of complications and/or adverse events following application of the multidisciplinary treatment. Results We performed 46 interventions on 45 patients diagnosed with peritoneal carcinomatosis from different causes, mainly ovarian cancer (83%). Paclitaxel was the most-used drug (35 interventions). There was no associated mortality, the average intervention time was 6.4hours and the average hospital stay 7days. We recorded adverse effects for 42 procedures, being grade 3-4 in 28.3% of the patients. The severe adverse events were: 10.9% gastrointestinal, 10.9% infectious, 6.5% haemorrhage or bleeding, 6.5% medullary toxicity, 4.4% respiratory, 2.2% coagulation and 2.2% hepatobiliary disorders. One patient developed grade III neutropaenia, probably associated with cisplatin. Conclusion The morbidity and mortality is in line with the average of published studies, and has mainly been attributed to surgical complications. Toxicity data lower than other studies can be due to using more tolerable chemotherapy regimens, not including drug combinations and given that paclitaxel was the main drug (AU)

[Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy associated toxicity in treatment of peritoneal carcinomatosis]. / Toxicidad asociada a la cirugía citorreductora y quimioterapia intraperitoneal hipertérmica en el tratamiento de la carcinomatosis peritoneal.

INTRODUCTION: Peritoneal carcinomatosis is a form of intra-abdominal dissemination of several tumours, which is associated with a poor prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is an alternative treatment. The aim of this study is to describe the toxicity associated with this procedure in patients with peritoneal carcinomatosis. METHOD: We conducted a descriptive, retrospective, single-centre study, including all patients undergoing this procedure between December 2007 and January 2010. The following data were recorded: anthropometric data, personal and surgical events, indication, previous treatments, extent of carcinomatosis, intervention duration, hospital stay, and type of complications and/or adverse events following application of the multidisciplinary treatment. RESULTS: We performed 46 interventions on 45 patients diagnosed with peritoneal carcinomatosis from different causes, mainly ovarian cancer (83%). Paclitaxel was the most-used drug (35 interventions). There was no associated mortality, the average intervention time was 6.4 hours and the average hospital stay 7 days. We recorded adverse effects for 42 procedures, being grade 3-4 in 28.3% of the patients. The severe adverse events were: 10.9% gastrointestinal, 10.9% infectious, 6.5% haemorrhage or bleeding, 6.5% medullary toxicity, 4.4% respiratory, 2.2% coagulation and 2.2% hepatobiliary disorders. One patient developed grade III neutropaenia, probably associated with cisplatin. CONCLUSION: The morbidity and mortality is in line with the average of published studies, and has mainly been attributed to surgical complications. Toxicity data lower than other studies can be due to using more tolerable chemotherapy regimens, not including drug combinations and given that paclitaxel was the main drug.

Experiencia de uso de partículas DC Bead ® cargadas con doxorrubicina en quimioembolización hepática / Experience Using Doxorubicin-Loaded DC Beads ® During Hepatic Chemoembolisation

Introducción El carcinoma hepatocelular es el más común y agresivo del grupo de tumores hepatobiliares. La quimioembolización hepática con partículas DC Bead® cargadas de doxorrubicina es un tipo de terapia local para pacientes con nódulos localizados, no susceptibles de cirugía. El objetivo de este estudio es describir las situaciones clínicas en las que se ha utilizado este procedimiento y su toxicidad temprana. Métodos Estudio descriptivo retrospectivo de los pacientes tratados con partículas DC Bead® cargadas de doxorrubicina en quimioembolización hepática desde octubre de 2006 hasta julio de 2009. Los datos se obtuvieron del programa Farhos Oncología® y las historias clínicas. Resultados Durante el periodo de estudio fueron tratados 21 pacientes, 15 hombres y 6 mujeres con una mediana de edad de 66 años. El diagnóstico que motivó la utilización de la técnica fue hepatocarcinoma no resecable. Del total de pacientes, 6 se encontraban en lista de espera para trasplante hepático. Los pacientes fueron clasificados según el sistema Child-Pugh: 15 pacientes en el grupo A, 5 en el grupo B y uno en el C, y según el Sistema Okuda: 14 pertenecían al grupo I, 6 al grupo II y uno al grupo III. La toxicidad más frecuente fue la aparición de síndrome posquimioembolización en 16 pacientes, que se resolvió con medicación sintomática. Discusión La utilización de doxorrubicina cargada en microesferas DC Bead® en quimioembolización transarterial se ha ajustado a usos con evidencias científicas y ha sido bien tolerado en todos los pacientes. Las incidencias durante la administración fueron leves y se resolvieron con medicación sintomática (AU)

Introduction Hepatocellular carcinoma is the most common and aggressive liver and biliary tumour. Hepatic chemoembolisation with doxorubicin-loaded DC Beads® is a local therapy for patients with localised nodes, which are not suitable for surgery. The objective of this study is to describe the clinical situations in which this procedure has been used and its early toxicity. Methods Retrospective descriptive study of patients treated with doxorubicin-loaded DC Beads® undergoing hepatic chemoembolisation from October 2006 until July 2009. Data were taken from the Farhos Oncología® programme and clinical histories. Results Twenty-two patients were treated during the study period, 15 men and 6 women, with an average age of 66 years. This technique was used for patients diagnosed with unresectable liver cancer. Out of the patient total, 6 were on the liver transplant waiting list. Patients were assessed using the Child–Pugh score: 15 patients in group A, 5 in group B and 1 in group C; and according to Okuda staging system: 14 were in group I, 6 in group II and 1 in group III. The most common toxicity was post-chemoembolisation in 16 patients, who were treated with symptomatic medication. Discussion Using doxorubicin-loaded microspherical DC Beads® during transarterial chemoembolisation has been adapted to use with scientific evidence and tolerated by all patients. Incidences during administration were mild and were resolved with symptomatic medication (AU)

[Experience using doxorubicin-loaded DC Beads® during hepatic chemoembolisation]. / Experiencia de uso de partículas DC Bead® cargadas con doxorrubicina en quimioembolización hepática.

INTRODUCTION: Hepatocellular carcinoma is the most common and aggressive liver and biliary tumour. Hepatic chemoembolisation with doxorubicin-loaded DC Beads(®) is a local therapy for patients with localised nodes, which are not suitable for surgery. The objective of this study is to describe the clinical situations in which this procedure has been used and its early toxicity. METHODS: Retrospective descriptive study of patients treated with doxorubicin-loaded DC Beads(®) undergoing hepatic chemoembolisation from October 2006 until July 2009. Data were taken from the Farhos Oncología(®) programme and clinical histories. RESULTS: Twenty-two patients were treated during the study period, 15 men and 6 women, with an average age of 66 years. This technique was used for patients diagnosed with unresectable liver cancer. Out of the patient total, 6 were on the liver transplant waiting list. Patients were assessed using the Child-Pugh score: 15 patients in group A, 5 in group B and 1 in group C; and according to Okuda staging system: 14 were in group I, 6 in group II and 1 in group III. The most common toxicity was post-chemoembolisation in 16 patients, which were treated with symptomatic medication. DISCUSSION: Using doxorubicin-loaded microspherical DC Beads(®) during transarterial chemoembolisation has been adapted to uses with scientific evidence and tolerated by all patients. Incidences during administration were mild and were resolved with symptomatic medication.

[Therapeutic use and profile of toxicity of the FOLFOX4 regimen]. / Uso terapéutico y perfil de toxicidad del esquema FOLFOX4.

INTRODUCTION: Since the publication of the MOSAIC test results in 2004, the FOLFOX4 regimen has been established as an adjuvant treatment which is recommended in stage III colorectal cancer. The aim of this study is to assess the use of this regimen in our field and to describe its toxicity. METHODS: Descriptive study of treatments with FOLFOX4 prescribed between April 2005 and March 2007. The data was obtained from the Farhos Oncología programme and clinical records. The following data was collected: age, gender, diagnosis, stage of the illness (TNM classification) and adverse reactions, expressing severity according to Common Toxicity Criteria 2.0. RESULTS: The FOLFOX4 regimen was prescribed for 39 patients (24 men and 15 women) with an average age of 59. The diagnoses were: 28 colon cancer (4 stage II, 17 stage III, and 7 stage IV), 10 rectal cancer (1 stage II, 4 stage III, and 5 stage IV) and 1 stage IV gastric cancer. The most frequent adverse reactions were peripheral neuropathy (82 %), neutropenia (56.4 %) and diarrhoea (53.9 %.) When the study was completed, 9 patients continued active treatment with the regimen (average 6.8 cycles.) Of the 30 remaining patients only 16 people completed the 12 planned cycles. 14 patients stopped their treatment (an average of 8.1 cycles) due to toxicity in 10 cases, clinical progression in 3 cases and one patient died. Of the total 368 cycles administered, 68 suffered administration delays and 22 had the dosage reduced. CONCLUSION: The use of the FOLFOX4 regimen has been adjusted to uses with some solid scientific evidence, but its toxicity has limited its use and has made administering the planned dosage levels difficult.

Uso terapéutico y perfil de toxicidad del esquema FOLFOX4* / Therapeutic use and profile of toxicity of the FOLFOX4 regimen

Introducción: Desde la publicación de los resultados del estudio MOSAIC en 2004, el esquema FOLFOX4 se ha establecido como un tratamiento adyuvante recomendado en los cánceres colorrectales estadio III. El objetivo de este estudio es valorar la utilización de este esquema en nuestro ámbito y describir su toxicidad. Métodos: Estudio descriptivo de los tratamientos con FOLFOX4 prescritos desde abril de 2005 a marzo de 2007. Los datos se obtuvieron del programa Farhos Oncología® y las historias clínicas. Se recogieron las variables siguientes: edad, sexo, diagnóstico, estadio de la enfermedad (clasificación TNM) y reacciones adversas, expresando su gravedad según los Common Toxicity Criteria 2.0. Resultados: El esquema FOLFOX4 ha sido prescrito a 39 pacientes (24 varones y 15 mujeres), con una mediana de edad de 59 años. Los diagnósticos fueron: 28 cáncer de colon (4 estadio II, 17 III y 7 IV), 10 cáncer de recto (1 estadio II, 4 III y 5 IV) y 1 cáncer gástrico estadio IV. Las reacciones adversas más frecuentes fueron neuropatía periférica (82 %), neutropenia (56,4 %) y diarrea (53,9 %). Al finalizar el estudio 9 pacientes seguían en tratamiento activo con este esquema (media, 6,8 ciclos). De los 30 restantes, sólo 16 completaron los 12 ciclos previstos. En 14 pacientes se suspendió el tratamiento (media, 8,1 ciclos), siendo los motivos: toxicidad en 10 casos, progresión clínica en 3 y fallecimiento en 1. Del total de los 368 ciclos administrados, 68 tuvieron retrasos en la administración y en 22 se redujo la dosis. Conclusión: La utilización del esquema FOLFOX4 se ha ajustado a usos con unas evidencias científicas sólidas, pero su toxicidad ha limitado el uso y dificultado la administración de la intensidad de dosis prevista (AU)

Introduction: Since the publication of the MOSAIC test results in 2004, the FOLFOX4 regimen has been established as an adjuvant treatment which is recommended in stage III colorectal cancer. The aim of this study is to assess the use of this regimen in our field and to describe its toxicity. Methods: Descriptive study of treatments with FOLFOX4 prescribed between April 2005 and March 2007. The data was obtained from the Farhos Oncología® programme and clinical records. The following data was collected: age, gender, diagnosis, stage of the illness (TNM classification) and adverse reactions, expressing severity according to Common Toxicity Criteria 2.0. Results: The FOLFOX4 regimen was prescribed for 39 patients (24 men and 15 women) with an average age of 59. The diagnoses were: 28 colon cancer (4 stage II, 17 stage III, and 7 stage IV), 10 rectal cancer (1 stage II, 4 stage III, and 5 stage IV) and 1 stage IV gastric cancer. The most frequent adverse reactions were peripheral neuropathy (82 %), neutropenia (56.4 %) and diarrhoea (53.9 %.) When the study was completed, 9 patients continued active treatment with the regimen (average 6.8 cycles.) Of the 30 remaining patients only 16 people completed the 12 planned cycles. 14 patients stopped their treatment (an average of 8.1 cycles) due to toxicity in 10 cases, clinical progression in 3 cases and one patient died. Of the total 368 cycles administered, 68 suffered administration delays and 22 had the dosage reduced. Conclusion: The use of the FOLFOX4 regimen has been adjusted to uses with some solid scientific evidence, but its toxicity has limited its use and has made administering the planned dosage levels difficult (AU)

[Prescription errors in chemotherapy]. / Errores de prescripción en quimioterapia.

OBJECTIVE: To describe and analyse the role of the pharmacy department in detecting errors in the prescription of cytostatic drugs. METHOD: A retrospective study was carried out over a two year period (2003-2004), which reviewed the errors detected by pharmacists in chemotherapy prescriptions. Medication errors were classified according to the system published by Otero et al. in the paper OErrores de medicaci-n: estandarizaci-n de la terminolog a y clasificaci-nO (Medication errors: standardizing the terminology and taxonomy). RESULTS: During the period analysed, 43,188 doses of parenteral cytostatic drugs were prepared for the treatment of 3,959 patients. A total of 135 errors were detected (3.1/1,000 preparations). Errors were distributed as follows: incorrect dose (38.5%), drug omission (21.5%), incorrect drug (11.1%), frequency error and incorrect treatment duration (9.6% each), incorrect patient (7.4%), incorrect administration rate (1.5%) and incorrect administration route (0.7%). All of the errors would be classified with a B level of seriousness, since they were resolved in the pharmacy department before dispensing the drugs. At least 66 of these could be classified as potential adverse drug events. Furthermore, 11 cases of incorrect reductions in doses and 12 cases of omissions of cytostatic drugs were detected and these errors could lead to a possible reduced treatment efficiency. CONCLUSIONS: Despite the low incidence of errors detected in chemotherapy prescriptions, their potential seriousness gives the pharmaceutical validation process a key role in improving safety for patients.

Errores de prescripción en quimioterapia / No disponible

Objetivo: Describir y analizar la contribución del servicio de farmacia en la detección de errores en la prescripción de tratamientos citostáticos. Método: Se realizó un estudio retrospectivo, revisando los errores detectados por el farmacéutico en las prescripciones de quimioterapia recibidas durante los años 2003 y 2004. Para la clasificación de los errores de medicación detectados se utilizó la taxonomía publicada por Otero y cols., recogida en el documento “Errores de medicación: estandarización de la terminología y clasificación”. Resultados: Durante el periodo estudiado se han preparado en nuestro servicio 43.188 dosis de citostáticos parenterales, para 3.959 pacientes. El número total de errores detectados ha sido de 135 (3,1/1.000 preparaciones). La distribución de los errores es la siguiente: dosis incorrecta 38,5%, omisión de medicamento 21,5%, medicamento erróneo 11,1%, frecuencia errónea y duración incorrecta 9,6% cada uno, paciente erróneo 7,4%, velocidad de administración incorrecta 1,5% y vía de administración incorrecta 0,7%. Todos los errores se clasificarían como categoría de gravedad B, ya que se solventaron en el servicio de farmacia antes de dispensar los medicamentos. Destacar que al menos 66 de ellos podrían clasificarse como acontecimiento adverso potencial. Señalar también que en 11 casos se detectaron reducciones erróneas de dosis y en 12 omisiones de citostáticos, lo que conlleva una posible disminución de eficacia terapéutica. Conclusiones: A pesar de la baja incidencia de errores detectados en la prescripción de quimioterapia, la gravedad potencial de los mismos convierte el proceso de validación farmacéutica en un punto clave para mejorar la seguridad del paciente

Objective: To describe and analyse the role of the pharmacy department in detecting errors in the prescription of cytostatic drugs. Method: A retrospective study was carried out over a two year period (2003-2004), which reviewed the errors detected by pharmacists in chemotherapy prescriptions. Medication errors were classified according to the system published by Otero et al. in the paper “Errores de medicación: estandarización de la terminología y clasificación” (Medication errors: standardizing the terminology and taxonomy). Results: During the period analysed, 43,188 doses of parenteral cytostatic drugs were prepared for the treatment of 3,959 patients. A total of 135 errors were detected (3.1/1,000 preparations). Errors were distributed as follows: incorrect dose (38.5%), drug omission (21.5%), incorrect drug (11.1%), frequency error and incorrect treatment duration (9.6% each), incorrect patient (7.4%), incorrect administration rate (1.5%) and incorrect administration route (0.7%). All of the errors would be classified with a B level of seriousness, since they were resolved in the pharmacy department before dispensing the drugs. At least 66 of these could be classified as potential adverse drug events. Furthermore, 11 cases of incorrect reductions in doses and 12 cases of omissions of cytostatic drugs were detected and these errors could lead to a possible reduced treatment efficiency. Conclusions: Despite the low incidence of errors detected in chemotherapy prescriptions, their potential seriousness gives the pharmaceutical validation process a key role in improving safety for patients

[Role of allopurinol and rofecoxib in agranulocytosis and acute tubular necrosis]. / Implicación de alopurinol y rofecoxib en agranulocitosis y necrosis tubular aguda.

OBJECTIVE: To report the case of a patient who developed a life-threatening agranulocytosis and acute tubular necrosis after the administration of allopurinol and rofecoxib. CASE REPORT: After minor surgery, a 70-year-old male underwent a routine blood test which encountered: anemia, leucopenia, neutropenia, thrombopenia, and altered creatinine levels. Both marrow and renal biopsies were performed, yielding the following results: acute tubular necrosis and agranulocytosis in the recovery stage. One month and a half before the aforementioned surgery a routine blood test had been performed, which showed normal values. The patient had then received allopurinol 100 mg/day for around 2 months, and rofecoxib 2.5 mg/day for 14 days. DISCUSSION: After ruling out other possible causes, a diagnosis of iatrogenically induced agranulocytosis and acute tubular necrosis was reached. We used a (modified) Karch-Lasagna algorithm with both drugs, and found the following imputability values: possible for rofecoxib and probable for allopurinol. In view of the widespread use of rofecoxib and COX-2 inhibitors, despite their recent availability, and of their potential role in the severe adverse effects discussed, healthcare professionals must be on the alert for the development of symptoms suggesting said or other adverse effects.

Implicación de alopurinol y rofecoxib en agranulocitosis y necrosis tubular aguda / Role of allopurinol and rofecoxib in agranulocytosis and acute tubular necrosis

Objetivo: Describir el caso de un paciente que desarrolló una agranulocitosis y una necrosis tubular aguda que comprometió su vida tras la administración de alopurinol y rofecoxib. Descripción del caso: Varón de 70 años, al que se le realizó una analítica de control tras una intervención menor, observándose anemia, leucopenia, neutropenia, trombopenia y alteración de los niveles de creatinina. Se efectuó biopsia renal y medular con el resultado de necrosis tubular aguda y médula compatible con agranulocitosis en fase de recuperación. Mes y medio antes de la intervención indicada se le había realizado una analítica de control encontrando valores dentro de la normalidad. Anteriormente el paciente había iniciado tratamiento con alopurinol 100 mg al día durante aproximadamente 2 meses, y rofecoxib 2,5 mg al día durante 14 días. Comentario: Tras descartar otras posibles causas, se llegó al diagnóstico de agranulocitosis y necrosis tubular aguda de origen iatrogénico. Aplicamos el algoritmo de Karsch-Lasagna (modificado) para ambos fármacos, encontrando los siguientes valores de imputabilidad: posible para el rofecoxib y probable para el alopurinol. Debido al amplio uso de rofecoxib y los inhibidores de la COX-2, a pesar de su reciente comercialización, y su posible implicación en los graves efectos adversos descritos, los profesionales sanitarios deben estar alertados ante la aparición de síntomas que puedan hacer sospechar la aparición de éstos u otros efectos adversos (AU)

Farmacología de los endectocidas: aplicaciones terapeúticas (II) / Pharmacology of endectocides: therapeutic use (II)

El presente artículo es el segundo y último dedicado a una revisión sobre los endectocidas. En este artículo se habla del mecanismo de acción, los efectos, aplicaciones y toxicidad de los endectocidas. (AU)