Reações adversas medicamentosas em pacientes em quimioterapia e estratégias de intervenções / Adverse drug reactions in chemotherapy patients and intervention strategies / Reacciones adversas a medicamentos en pacientes quimioterápicos y estrategias de intervención

A quimioterapia do câncer pode ocasionar reações adversas medicamentosas (RAM), podendo resultar de interações medicamentosas (IM) e impactar na adesão. O presente estudo relatou as RAM apresentadas por pacientes em quimioterapia (QT) e propôs estratégias de intervenções. Este trabalho foi aprovado em comité de ética (5.160.503), sendo incluídos 23 pacientes em quimioterapia (oral- VO e/ou endovenosa- EV) e todos foram entrevistados. Recebiam apenas o QTEV, 20 pacientes e 2 QTEV e VO, a maioria em tratamento paliativo (50%), predomínio de estadiamento IV, sendo as doenças mais presentes de pâncreas (27,3%), estômago (22,7%) e mama (18,2%) e esquema mais usado foi Carboplatina + Paclitaxel. As principais comorbidades foram diabetes e hipertensão arterial. As interações medicamentosas foram classificadas em graves (45%), moderadas (55%) e intencional (75%), sendo necessário introdução de medicamentos de suporte (61%). Houve RAM de maior gravidade, neutropenia, sendo necessário a suspensão temporária, e de menor gravidade náuseas. Houve um óbito relacionado a evolução de doença e, talvez, o tratamento possa ter contribuído. Ao final, foram feitas as intervenções para cada caso e validado o formulário para a consulta farmacêutica a pacientes oncológicos.

Cancer chemotherapy can cause adverse drug reactions (ADRs), which can result from drug interactions (IM) and impact adherence. The present study reported the ADRs presented by patients undergoing chemotherapy (CT) and proposed intervention strategies. This work was approved by the ethics committee (5,160,503), and 23 patients on chemotherapy (oral-VO and/or intravenous-IV) were included and all were interviewed. Only received CTIV, 20 patients and 2 CTIV and VO, most in palliative treatment (50%), predominance of stage IV, being the most common diseases of pancreas (27.3%), stomach (22.7%) and breast (18.2%) and the most used regimen was Carboplatin + Paclitaxel. The main comorbidities were diabetes and arterial hypertension. Drug interactions were classified as severe (45%), moderate (55%) and intentional (75%), requiring the introduction of supportive drugs (61%). There were more severe ADRs, neutropenia, requiring temporary suspension, and less severe nausea. There was one death related to the evolution of the disease and, perhaps, the treatment may have contributed. At the end, interventions were made for each case and the form for the pharmaceutical consultation to cancer patients was validated.

La quimioterapia contra el cáncer puede causar reacciones adversas a los medicamentos (RAM), que pueden ser consecuencia de interacciones farmacológicas (IM) y repercutir en la adherencia. El presente estudio reportó las RAM presentadas por pacientes en quimioterapia (QT) y propuso estrategias de intervención. Este trabajo fue aprobado en comité de ética (5.160.503), se incluyeron 23 pacientes en quimioterapia (oral- VO y/o endovenosa-EV) y todos fueron entrevistados. Recibieron sólo QTEV, 20 pacientes y 2 QTEV y VO, la mayoría en tratamiento paliativo (50%), predominio de estadiaje IV, siendo las enfermedades más presentes las de páncreas (27,3%), estómago (22,7%) y mama (18,2%) y el esquema más utilizado fue Carboplatino + Paclitaxel. Las principales comorbilidades fueron la diabetes y la hipertensión arterial. Las interacciones farmacológicas se clasificaron como graves (45%), moderadas (55%) e intencionadas (75%), requiriendo la introducción de fármacos de apoyo (61%). La RAM más grave fue la neutropenia, que requirió la suspensión temporal, y la menos grave las náuseas. Hubo una muerte relacionada con la evolución de la enfermedad y, tal vez, el tratamiento pudo haber contribuido. Al final, se realizaron intervenciones para cada caso y se validó el formulario de consulta farmacéutica a pacientes oncológicos.

Medicações ototóxicas utilizadas no tratamento oncológico pediátrico: uma revisão sistemática / Ototoxic medications used in treating childhood cancer: a systematic review

RESUMO Objetivo Fazer um levantamento dos medicamentos ototóxicos utilizados no tratamento do câncer pediátrico, apontar os danos das drogas para o sistema auditivo e os métodos utilizados na identificação destes danos nessa população. Estratégia de pesquisa: Foram utilizados periódicos nacionais e internacionais pertinentes ao assunto, acessados eletronicamente em bases de dados da Biblioteca Virtual em Saúde - MS, PubMed, Biblioteca Digital Brasileira de Teses e Dissertações, que envolvessem a população pediátrica com histórico de tratamento oncológico, publicados entre 2007 e 2016, e no Banco de Teses e Dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Critérios de seleção Foram selecionados estudos que contemplassem os seguintes critérios: estudos observacionais nas línguas portuguesa, inglesa ou espanhola e resumos disponíveis que informassem o método de avaliação do dano auditivo. Resultados A amostra final resultou em 12 artigos. Destes, a audiometria tonal limiar foi o método de avaliação auditiva mais utilizado, estando presente em 10 (84,61%) dos estudos, seguido das emissões otoacústicas (46,15%). Todos os estudos foram desenvolvidos com pacientes que fizeram uso de cisplatina ou derivados da platina e, quanto ao dano auditivo, apenas 1 dos estudos incluídos não relatou presença de alteração na população estudada. Conclusão Os derivados da platina expressam papel importante no tratamento do câncer em diversos níveis e são os agentes ototóxicos mais citados em pesquisas. A cóclea é o local mais afetado, mais especificamente as células ciliadas externas. Os métodos de investigação da alteração auditiva mais utilizados são a audiometria tonal limiar e as emissões otoacústicas.

ABSTRACT Objective The aim of the present study was to perform a literature review on ototoxic medications used for the treatment of childhood cancer and determine the harm caused by such drugs to the auditory system as well as the methods used to identify this harm. Search strategy The electronic databases of the Virtual Health Library (Brazilian Health Ministry), PubMed, Brazilian Digital Library of Theses and Dissertations, and Databank of Theses and Dissertations of the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES [Brazilian Coordination for the Advancement of Higher Education Personnel]) were searched for relevant national and international papers involving the pediatric population with a history of treatment for cancer published between 2007 and 2016. Selection criteria Observational studies published in Portuguese, English or Spanish with abstracts available and that informed the method for assessing hearing damage. Results The final sample consisted of 12 articles. Pure-tone threshold audiometry was the used in ten (84.61%) of the studies and otoacoustic emissions were investigated in 46.15%. All studies involved patients who made use of cisplatin or platinum derivatives. Only one of the studies included in the present review reported no changes in hearing in the population studied. Conclusion Platinum derivatives play an important role in the treatment of cancer and are the most widely cited ototoxic agents in studies. The cochlea is the most affected site, specifically the outer hair cells. The most widely used methods for assessing altered hearing are pure-tone threshold audiometry and otoacoustic emissions.

Severe aseptic orbital cellulitis with subtenon carboplatin for intraocular retinoblastoma.

Retinoblastoma is a rare intraocular tumor of childhood. Chemoreduction followed by laser or cryotherapy is the treatment of choice. Subtenon carboplatin injection is also an accepted treatment modality for vitreous seeds, along with systemic chemotherapy. Transient periocular edema, optic neuropathy and fibrosis of orbital tissues are the known side effects of subteneon carboplatin injection. We report a case of severe aseptic orbital cellulitis with necrosis and prolapse of the conjunctiva 48 h after the injection, which resolved well on only conservative management.

Case report and review of literature: temporary asymptomatic sinus bradycardia with carboplatin, paclitaxel and bevacizumab: under-reported in clinical trials and under-disclosed in practice

Paclitaxel, Carboplatin, and Bevacizumab [PCB] is one of the standard chemotherapy regimens for the treatment of non-small cell lung cancer. Temporary asymptomatic bradycardia is recognized toxicity of paclitaxel. However, it is under-disclosed to patients during consent for treatment and is under-reported in clinical phase III trials. Here, were report a case of severe but temporary asymptomatic sinus bradycardia [heart rate 39 bpm] in a patient immediately after receiving PCB. The patient was not informed of this risk during consent to therapy leading to non-compliance with future plan of management. Literature search showed that bradycardia is documented. However, it is not reported adequately in land mark phase III trials' reports. The cause of bradycardia in this patient is probably paclitaxel. Oncologists should disclose this potential risk to patients during consent to chemotherapy. Investigators should monitor and report it when conducting land mark trials

A Case of Pseudomenbranous Colitis after Paclitaxel and Carboplatin Chemotherapy / 대한소화기학회지

Antibiotics-associated pseudomembranous colitis is well documented and caused by abnormal overgrowth of toxin producing Clostridium difficile colonizing the large bowel of patients undergoing antibiotic therapy. Administration of chemotherapeutic agents is frequently complicated by diarrhea and enterocolitis. However, pseudomembranous colitis related to chemotherapeutic agent usage is very rare. We experienced a 67 old-years male patient diagnosed of non-small cell lung carcinoma who complained of watery diarrhea and abdominal pain after treated with paclitaxel and carboplatin. Sigmoidoscopic examination revealed diffusely scattered, whitish to yellowish pseudo-membrane with background edematous hyperemic mucosa from sigmoid colon to rectum. Histopathologic findings were consistent with pseudomembranous colitis as typical volcano-like exudate. The symptoms improved after stopping chemotherapy and treatment with metronidazole. In patients with persistent diarrhea and abdominal pain after receiving chemotherapy agents, although rare, pseudomembranous colitis should be considered as a differential diagnosis.

Emissões otoacústicas evocadas por estímulo transiente em crianças portadoras de retinoblastoma submetidas a tratamento quimioterápico com carboplatina / Transient otoacoustic emissions in childrens with retinoblastoma submitted to chemiotherapy with carboplatin

Verificar a ocorrência de emissões otoacústicas por estímulo transiente, em pacientes portadores de retinoblastoma, submetidos a tratamento quimioterápico com carboplatina. Foram avaliados 18 indivícuos com idades entre nove meses e nove anos...

To verify the occurence of transient otoacoustic emissions in carrying patients of retinoblastoma, submitted the chemotherapy treatment with carboplatin. From 18 evaluated subjets with ages between nine months and nine years...

Determination of carboplatin dose by area under the curve in combination chemotherapy for senile non-small cell lung cancer / 华中科技大学学报（医学）（英德文版）

To preliminarily determine the appropriate dosage of carboplatin (CBP) at AUC of 5 mg.Ml(-1).min(-1) in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer (NSCLC). Thirty-five Chinese senile patients with NSCLC in advanced stage (III/IV) were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol+CBP, Gemzar+CBP and NVB+CBP. The dose of CBP was at 5 mg.mL(-1).min(-1) of area under the concentration-time curve (AUC). Side effects and quality of life were observed before and after the chemotherapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granulocytopenia was found in 47.9% (46/96) of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% (27/96) of the subjects. However, other side effects were slight. The mean score of quality of life (QOL), according to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg.mL(-1).min(-1) by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg.mL(-1).min(-1) by AUC may be too high for Chinese senile patients with non-small cell lung cancer.

Granulocyte-colony stimulating factors for secondary prevention of leucopenia in patients receiving chemotherapy.

OBJECTIVE: To evaluate the effectiveness of GCSF as a secondary preventive adjunct to chemotherapy in the gynaecologic cancer patients who previously had grade 3-4 neutropenia or leucopenia from chemotherapy. MATERIAL AND METHOD: We retrospectively reviewed the medical records of 94 chemotherapeutic cycles with GCSF as secondary prophylaxis in 29 patients with gynaecologic malignancy between January 1996 and April 2005. RESULTS: The median age of the patients was 51 years (21-75). Most of the patients had ovarian cancers (19 cases, 65.6%). From secondary GCSF, grade 4 neutropenia was developed in 12 of 94 cycles (12.8%), and grade 4 leucopenia was developed in 5 of 94 cycles (5.3%). There were no patients developing febrile neutropenia after GCSF support. CONCLUSION: Secondary GCSF prophylaxis was effective in preventing grade 4 leucopenia, grade 4 neutropenia, and febrile neutropenia.

Concurrent weekly paclitaxel/carboplatin and split course thoracic radiation therapy in unresectable stage III A/B non-small cell lung cancer

This phase II study was conducted to assess tolerance and efficacy of concurrent weekly paclitaxel and carboplatin with split course thoracic irradiation in patients with locally advanced unresectable non-small cell lung cancer [NSCLC]. Patients with histologically confirmed unresectable stage IIIA/IIIB NSCLC with Karnofsky performance status of >/ 70 and weight loss /<5% with no palpable supraclavicular lymph nodes were treated with thoracic irradiation, 2 Gy daily, 5 days/week for three weeks [total dose of 30 Gy], followed by 10 days rest and the dose was repeated for a total dose of 60 Gy. Concurrently with radiation, patients received weekly paclitaxel 45 mg/m2 and carboplatin 100 mg/m2 given on days 1, 8, 15, 30, 37 and 44. Response was assessed by chest CT scan 2 months after treatment was completed and survival was calculated from the time of start of treatment. Between October 1999 and August 2000, 29 patients were treated. The median age was 56 years, there were 22 males [75.9%] and 7 females [24.1%]. Ten patients [34.5%] had stage IIIA disease and 19 patients [65.5%] with stage IIIB. Regarding acute toxicity, only 1 patient [3.4%] suffered from grade 4 toxicity [neutropenia]. Grade 3 esophagitis, pneumonitis and neutropenia were reported in 17.2%, 20.7% and 17.2%, respectively. The overall response rate was 69% with 6.9% complete response and 62.1% partial response. The median overall survival was 16.8 mon., with 1 and 2 year survival rates of 58.6% and 31%, respectively. The recorded 1 year and 2 year progression free survival rates were 48.3% and 27.6%, respectively, with a median time of progression of 11 months. The study concluded that this treatment regimen produces high response and survival rates with modest toxicity in patients with locally advanced unresectable NSCLC and it must be compared either alone or preceded by induction chemotherapy with the standard cisplatin based chemoradiation treatment

Carboplatin and weekly paclitaxel in locally advanced [stage IIIB] and metastatic non-small-cell cancer [NSCLC]: a phase II pilot study

A phase II pilot study was conducted to determine the response, toxicity and survival rates of lung cancer patients treated with the combination carboplatin and weekly paclitaxel in stage IIIB and IV non-small-cell lung cancer [NSCLC]. A total of 19 cases were included in the current study. Paclitaxel was administered in a dose of 70 mg/m2 over 1 hour infusion weekly for 3 weeks, followed by 1 week of rest for each 4-week cycle for a total of four cycles. Carboplatin was administered in a dose of [area under the curve] AUC 6 day 1 each cycle following the paclitaxel. Assessment of treatment outcome was carried out following. An overall response rate was achieved in 36.8% of the cases [7/19], all of them were partial remissions and none of the patients achieved complete remission. Seven [36.8%] patients showed stationary disease and the remaining 5 [26.4%] patients showed disease progression. Treatment related toxicities encountered were mainly mild to moderate. Grade 3-4 neutropenia was reported in 3 [18.8%] patients, grade 3 anemia and thrombocytopenia were reported in two [10.5%] patients each. Neutropenic fever was encountered only in one [5.3%] patient. Grade 3 peripheral neuropathy and arthralgia/myalgia was reported in three [15.8%] patients. In general, treatment was well tolerated. Overall median survival was 10 months and 1-year overall survival was 42.5%. The median and 1-year progression free survival results were 8 months and 6.7%, respectively. Cox regression multivariate analysis of various prognostic factors revealed that response to treatment and presence of pleural effusion were significant and independent predictors of overall survival. The combination of carboplatin and weekly paclitaxel is an active and well tolerated regimen. The role of weekly paclitaxel in NSCLC should he better defined in future randomized studies

Alteraciones histopatológicas producidas por el carboplatino administrado subtenoniano vs intravítreo en conejos / Alterations histopathologics to produce by the carboplatin administration subtenoniano vs intravitreal in rabbint

El carboplatino es un análogo del cisplatino que forma enlaces cruzados de DNA-interfibra para reducir la actividad tumoral. Ha sido utilizado en el tratamiento del Retinoblastoma, el cual constituye el tumor intraocular más frecuente de la infancia. Su administración por vía sistémica ocasiona numerosos efectos adversos, es por ello que en los últimos tiempos se ha empleado en forma local logrando un gran avance en la reducción del tamaño de la tumoración, en este sentido, la quimiorreducción representa una alternativa en el manejo de ésta patología, sin embargo la administración por vía local no es efectiva en siembras vítreas ni subretinianas, teniendo que reforzar este tratamiento con quimioterapia o crioterapia, y a pesar de ello muchos de estos ojos terminan en enucleación. En búsqueda de procedimientos menos agresivos tanto locales como sistémicos, decidimos realizar este estudio para investigar el grado de toxicidad de este medicamento, principalmente en la retina y el resto de las estructuras oculares en conejos albinos de Nueva Zelanda, colocando dosis iguales por vía intravítrea y subtenoniana, obteniendo alteraciones en todas las estructuras oculares de los ojos de conejos en donde se administró la droga por vía intravítrea en comparación con los ojos de conejos donde se colocó carboplatino en cuyo caso no observamos altraciones histopalógicas de las estructuras oculares

Quimioterapia postoperatoria con carboplatino y etopósido en niños con meduloblastoma de alto riesgo / Postoperative chemotherapy with carboplatin and etoposide in children with high-risk medulloblastoma

Introducción. Se estudiaron prospectivamente diez pacientes con meduloblastoma de alto riesgo que recibrieron quimioterapia postoperatoria con carboplatino y etopósido previo a radioterapia. Material y métodos. Se realizaron a cada uno de los pacientes estudios de resonancia magnética de cráneo y neuroeje antes de iniciado el tratamiento y al concluir, con el fin de valorar la respuesta tumoral obtenida. Se deretminó el grado de toxicidad hematológica secundaria al tratamiento y se calculó la sobrevida actuarial obtenida. Resultados. Ocho pacientes presentaron una respuesta superior al 50 por ciento; la toxicidad hematológica se presentó en el 34.2 por ciento de los cursos administrados. La sobrevida actuarial obtenida a 18 meses fue del 57 por ciento en el mismo periodo. Conclusiones. La asociación de carboplatino y etopósido empleados en conjunto tienen un buen efecto antitumoral en este tipo de neoplasias con mínimos efectos colaterales y con la posibilidad de mejorar la sobrevida de los pacientes con meduloblastoma de alto riesgo