The prospects of DNA damage repair variants guiding platinum compounds in the treatment of triple negative breast cancer / 中华肿瘤杂志

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.

Criterios de inelegibilidad al uso de platinos en cáncer otorrinolaringológico, Guías 2021 / Criteria for ineligibility for the use of platinums in otorhino-laryngological cancer, Guidelines 2021

Introducción: el uso de sales de platinos en patologías oncológicas es ampliamente usado, una de las preocupaciones de los profesionales de la salud es la presencia de eventos adversos en este grupo de pacientes que suelen ser vulnerables, por lo que es necesario la generación de consensos para realizar una selección óptima de pacientes candidatos a terapias basadas en platinos Objetivo: Realizar un consenso de expertos para la inelegibilidad al uso de platinos de acuerdo a varios criterios para realizar un tratamiento óptimo de acuerdo a la selección y categorización de pacientes Pregunta de salud cubierta por la Guía: ¿Qué pacientes portadores de cáncer de origen otorrinolaringológico no son elegibles para tratamiento con platinos? Población: La población objetivos son pacientes adultos con cáncer otorrinolaringológico. Resultados: Se establecieron consensos para la inelegibilidad al uso de platinos sobre los siguientes criterios: Edad >70 años, ECOG >1, Pérdida involuntaria de peso >20%, función auditiva "borderline": alteraciones Grado I, Alteraciones neurológicas Grado I, Trastornos de la función renal: CrCL <60 ml/min, Alteración hepática ≥ grado II Child-Pugh B, Comorbilidades: diabetes, HTA, alteraciones pulmonares, anemia e Insuficiencia cardiaca

Introduction: the use of platinum salts in oncological pathologies is widely used, one of the concerns of health professionals is the presence of adverse events in this group of patients who are usually vulnerable, so it is necessary to generate of consensus to make an optimal selection of candidate patients for platinum-based therapies Objective: To carry out a consensus of experts for the ineligibility for the use of points according to several criteria to carry out an optimal treatment according to the selection and categorization of patients Health question covered by the Guide: Which patients with otorhinolringological origin cancer are not eligible for treatment with platinums? Population: The target population is adult patients with ENT cancer. Results: consensus was established for the ineligibility for the use of lenses on the following crite-ria: Age> 70 years, ECOG> 1, Involuntary weight loss> 20%, "borderline" hearing function: Grade I al-terations, Neurological alterations Grade I, Renal function disorders: CrCL <60 ml / min, Hepatic im-pairment ≥ grade II Child-Pugh B, Comorbidities: diabetes, hypertension, pulmonary disorders, anemia and heart failure.

Manejo e Prevenção de Reações Adversas da Quimioterapia Antineoplásica com Platinas em Pacientes com Cânceres Esofágico e Gástrico: Revisão Sistemática da Literatura / Management and Prevention of Adverse Reactions to Platinum Antineoplastic Chemotherapy in Patients with Esophageal and Gastric Cancer: Systematic Literature Review / Manejo y Prevención de Reacciones Adversas a la Quimioterapia Antineoplásica con Platino en Pacientes con Cánceres de Esófago y Gástrico: Revisión Sistemática de la Literatura

Introdução: O câncer gástrico é a quinta doença maligna mais comum em todo o mundo. Trata-se do tumor maligno mais incidente na Ásia, especialmente na China. O carcinoma esofágico é um dos tipos mais agressivos de tumor maligno. Os tratamentos multimodais, incluindo quimioterapia neoadjuvante e quimiorradioterapia, são utilizados e podem causar fadiga, vômito, diarreia, alterações cutâneas, caquexia e neuropatia periférica, que podem ser efeitos colaterais importantes para muitos pacientes que realizam seus tratamentos. Objetivo: Realizar uma revisão sistemática sobre o manejo e a prevenção de reações adversas da quimioterapia antineoplásica com platinas em pacientes com câncer esofágico e tumor gástrico. Método: Para seleção dos artigos, foi realizada a busca em três bases de dados: MEDLINE/PubMed, Cochrane e Embase, com a estratégia PICO, variando os descritores MeSH/DeCs e operadores booleanos. Resultados: Foram encontrados 455 títulos, dos quais, após utilizar a diretriz PRISMA, restaram 15 artigos para a revisão sistemática, que abordavam o manejo e a prevenção de náusea e vômitos, neuropatia periférica, caquexia, suplementação de magnésio, tratamento de depressão e toxicidade geral. Conclusão: Verificou-se que náuseas, vômitos, neuropatia e hipomagnesemia tiveram maior número de estudos relacionados ao manejo e à prevenção desses sintomas, nos quais identificaram-se algumas sugestões de condutas com maior evidência para essas reações. As demais reações encontradas ainda carecem de mais estudos, principalmente nos casos de cânceres gástrico e esofágico

Introduction: Gastric cancer is the fifth most common malignancy worldwide. It is the most frequent malignant tumor in Asia, especially in China. Esophageal carcinoma is one of the more aggressive types of malignant tumor. Multimodal treatments, including neoadjuvant chemotherapy and chemoradiotherapy are utilized and can cause fatigue, vomiting, diarrhea, skin changes, cachexia, and peripheral neuropathy, which can be important side effects for many patients undergoing their treatments. Objective: Carry out a systematic review on the management and prevention of adverse reactions of antineoplastic chemotherapy with platinum in patients with esophageal cancer and gastric tumor. Method: To select the articles, a search was conducted in three databases: MEDLINE/PubMed, Cochrane and Embase, with the PICO strategy, alternating between MeSH/DeCs descriptors and Boolean operators. Results: 455 titles were found, of which, after using the PRISMA guideline, 15 articles remained for systematic review, addressing the management and prevention of nausea and vomiting, peripheral neuropathy, cachexia, magnesium supplementation, treatment of depression and general toxicity. Conclusion: The greatest number of studies addressing the management and prevention of the symptoms of nausea, vomits, neuropathy and hypomagnesemia were found, and it was possible to identify some suggestions of conducts to treat these reactions. More studies are necessary for the other reactions encountered, mainly in the cases of gastric and esophageal cancer

Introducción: El cáncer gástrico es la quinta neoplasia maligna más común en todo el mundo. Es el tumor maligno más común en Asia, especialmente en China. El carcinoma de esófago es uno de los tipos de tumores malignos más agresivos. Se utilizan tratamientos multimodales, que incluyen quimioterapia neoadyuvante y quimiorradioterapia que pueden provocar: fatiga, vómitos, diarrea, alteraciones cutáneas, caquexia y neuropatía periférica, que pueden ser efectos secundarios importantes para muchos pacientes sometidos a sus tratamientos. Objetivo: Realizar una revisión sistemática sobre el manejo y prevención de reacciones adversas de la quimioterapia antineoplásica con platino en pacientes con cáncer de esófago y tumor gástrico. Método: Para la selección de los artículos se realizó una búsqueda en tres bases de datos: MEDLINE/PubMed, Cochrane y Embase, con la estrategia PICO, variando los descriptores MeSH/DeCs y operadores booleanos. Resultados: Se encontraron 455 títulos, de los cuales, luego de utilizar la guía PRISMA, quedaron 15 artículos para revisión sistemática, que abordaron el manejo y prevención de náuseas y vómitos, neuropatía periférica, caquexia, suplementación con magnesio, tratamiento de la depresión y toxicidad general. Conclusión: Se verifico que náuseas, vómitos, neuropatía e hipomagnesemia tuvieron un mayor número de estudios relacionados con el manejo y prevención de los síntomas, en los cuales fue posible identificar algunas sugerencias de conducta con mayor evidencia de estas reacciones. Las otras reacciones encontradas aún necesitan más estudios, especialmente en casos de cánceres gástrico y de esófago

Occupational noise-induced hearing loss in platinum miners: what do the data tell us?

Background: Occupational noise-induced hearing loss (ONIHL) is one of the most common occupational health diseases affecting miners in South Africa. Accurate and appropriate medical data are essential for making valid diagnoses. Objectives: The purpose of this study was to describe the electronic records of a South African platinum mine's audiometry medical surveillance system and their role in early diagnosis of ONIHL. Ear-related conditions of affected miners, occupations, and noise levels were concurrently reviewed, and the characteristics of miners with and without ONIHL were described. Methods: This was an analysis of secondary data from the electronic audiometry and employee occupational records of 305 platinum mine workers for the period 2014 to 2017. Data were analysed using descriptive statistics. Results: Although the audiometry records contained appropriate and relevant data, including annual hearing screening percentage loss of hearing (PLH) shifts, there was evidence of inaccurate and insufficient recording of risk factors for hearing loss in the medical surveillance records. The records indicated that the miners in some occupations were exposed to dangerously high noise levels, exceeding 85 dB(A). Miners as young as 21 years of age were diagnosed with ONIHL. Conclusion: The insufficient and inaccurate data captured in the miners' records has important implications for the mine's efficient implementation of hearing conservation programme (HCP) elements aimed at mitigating ONIHL. The hazardous noise levels recorded call for increased attempts to meet noise level regulations, while the presence of conditions such as pseudohypacusis highlights the need for exploration of more reliable assessment measures

Chemotherapy for advanced non-small cell lung cancer in the elderly population

ABSTRACT BACKGROUND: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs). As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV) NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (1966 to 31 October 2014), EMBASE (1974 to 31 October 2014), and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 31 October 2014). In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database. Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses. Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS), one-year survival rate (1yOS), progression-free survival (PFS), objective response rate (ORR), major adverse events, and quality of life (QoL). MAIN RESULTS: We included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials). Non-platinum single-agent versus non-platinum combination therapy Low-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence). Differences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data. Non-platinum therapy versus platinum combination therapy Platinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs). Effects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data. AUTHORS' CONCLUSIONS: In people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on survival. We are uncertain as to the comparability of their adverse event profiles. Additional evidence on quality of life gathered from additional studies is needed to help inform decision making

Delay of the Blink Reflex in Patients Receiving Platinum-Analogue Chemotherapy

OBJECTIVE: To investigate the presence of cranial neuropathy in patients with platinum-analogue chemotherapy using electrodiagnostic evaluations. METHODS: Thirty-nine patients whose chemotherapy was completed within a month and 40 control subjects were enrolled in the study. Electrodiagnostic evaluation was performed using sensory and motor nerve conduction studies and blink reflex studies, in addition to the two-point discrimination test. RESULTS: The chemotherapy group had significantly longer latencies of bilateral R1 responses (left p<0.001; right p<0.001) and greater distance in two-point discrimination (p<0.001) compared to the control group. In the subgroup with peripheral polyneuropathy, the left R1 (p=0.01), both R2i (left p=0.02; right p=0.03) and the left R2c (p=0.02) were prolonged relative to those without the polyneuropathy, and both R1 (left p<0.001; right p<0.001), R2i (left p=0.01; right p=0.03), and the left R2c (p=0.01) were prolonged relative to the controls. On the other hand, the subgroup without the polyneuropathy showed only prolongation of both R1 (left p=0.006; right p<0.001) relative to the controls. CONCLUSION: In the present study, comparison of blink reflex and two-point discrimination showed the likelihood of subclinical cranial neuropathy following platinum-analogue chemotherapy. Cranial neuropathy caused by platinum agents was more profound in patients with peripheral polyneuropathy and may be dependent on the cumulative dose of the drug. The blink reflex may be of value in detecting subclinical cranial neuropathy in patients undergoing platinum-analogue chemotherapy.

Relação entre perda auditiva e alterações genéticas em pacientes tratados de câncer na infância / Relations between hearing loss and genetic alterations in patients treated from cancer during childhood

A ototoxicidade é uma das sequelas do tratamento oncológico com uso de quimioterápicos derivados da platina cisplatina (CDDP) e carboplatina (CBDCA). Tal tratamento pode provocar a lesão do órgão periférico da audição acometendo a estria vascular e células ciliadas externas (CCE) do giro basal. A perda auditiva causada pela ototoxicidade é neurossensorial bilateral prejudicando inicialmente altas frequências e o seu uso contínuo pode acometer frequências ≤ 4 kHz prejudicando o reconhecimento de fala. Estudos recentes têm demonstrado uma associação entre algumas variantes genéticas e a toxicidade dos derivados da platina. O objetivo do nosso estudo foi identificar se há influência de fatores genéticos na perda auditiva encontrada em pacientes tratados de câncer na infância submetidos a quimioterápicos derivados da platina. Avaliamos a ocorrência de perda auditiva e sua associação com a dose de CDDP e CBDCA assim como, a associação entre a ototoxicidade e a presença das variantes MT-RNR1- m.1555A>G, GJB2-c.35delG, e GSTP1-c.313A>G. Material e Método: Foram selecionados pacientes que tiveram câncer na infância e estavam fora de tratamento por pelo menos cinco anos. Setenta e três pacientes preencheram os critérios e assinaram o termo de consentimento livre e esclarecido. Sessenta e um pacientes realizaram tratamento de risco para a audição com derivados da platina e 12 pacientes sem tratamento de risco para audição. Todos realizaram avaliação audiológica...

Ototoxicity is one of the adverse effects in the oncological treatment using chemotherapy with platin agents such cisplatin (CDDP) and/or carboplatin (CBDCA). Such treatment may lead to end organ lesions in the auditory system involving the stria vascularis and outer hair cells, mainly at the basal turn. Hearing loss caused by ototoxicity is bilateral, sensorineural affecting initially the high frequencies, but it may progress to frequencies below 4 kHz and compromise the speech recognition. Recent studies have demonstrated that the association of some genetic variants with the toxicity of platin agents. The aim of this study was to identify whether there is any influence of genetic factors on the hearing loss found in patients treated from cancer during childhood with platin agents. The occurrence of hearing loss and its association with the cisplatin and carboplatin dosages, as well as the presence of variants of A1555G in the mitochondrial gene MT-RNR1 (12S rRNA), 35delG in the GJB2 gene, and c.313A>G in the GSTP1 gene were evaluated. Material and Methods: Patients who had cancer during childhood, who were released from treatment for at least 5 years were selected. Seventy-three patients fullfilled the criteria and signed the...

Research progress of the drug delivery system of antitumor platinum drugs with macrocyclic compounds / 药学学报

Platinum-based anticancer drugs have been becoming one of the most effective drugs for clinical treatment of malignant tumors for its unique mechanism of action and broad range of anticancer spectrum. But, there are still several problems such as side effects, drug resistance/cross resistance and no-specific targeting, becoming obstacles to restrict its expanding of clinical application. In recent years, supramolecular chemistry drug delivery systems have been gradually concerned for their favorable safety and low toxicity. Supramolecular macrocycles-platinum complexes increased the water solubility, stability and safety of traditional platinum drugs, and have become hot focus of developing novel platinum-based anticancer drugs because of its potential targeting of tumor tissues/organs. This article concentrates in the research progress of the new drug delivery system between platinum-based anticancer drugs with three generations of macrocycles: crown ether, cyclodextrin, cucurbituril and calixarene.

Relationship between Quality of Life and Nurse-led Bedside Symptom Evaluations in Patients with Chemotherapy-induced Peripheral Neuropathy

PURPOSE: This cross-sectional study aimed at determining the relationship between patient-reported quality of life (QOL) and nurse-led bedside evaluations of chemotherapy-induced peripheral neuropathy symptoms. METHODS: One hundred ninety-five patients treated at the oncology clinic at our institution were assessed using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity and nurse-led bedside examinations. The relationship between self-reported QOL and bedside examinations was evaluated using Spearman rank correlations. RESULTS: Scores of upper and lower extremity muscle strength based on the bedside examinations showed a weak negative correlation with the emotional well-being subscale of Functional Assessment of Cancer Therapy-General. Further, weak negative relationships were present between QOL and the following nurse-reported parameters: vibration perception in the hand, upper extremity muscle strength, touch and vibration perception in the feet, and tendon reflexes. CONCLUSION: Collectively, our results indicate that nurse-led bedside evaluation is a noninvasive and useful method for detecting neurotoxicity and evaluating the patient's QOL both during and after treatment.

Data Analysis for Anti-Neoplastic Chemotherapy-Related Adverse Events Reported to the Korean Pharmacovigilance Regional Network / 대한내과학회지

BACKGROUND/AIMS: To describe the toxicity profile of anti-neoplastic agents from real clinical settings, we analyzed spontaneously reported adverse events (AEs) using data from the adverse drug reaction (ADR) reporting system of the Korean Food and Drug Administration (KFDA). METHODS: Data were extracted from the nationwide spontaneous ADR reporting system of KFDA from July 2009 to December 2010. We extracted and analyzed data related to chemotherapy and identified unlabeled ADR that were not described in the package insert of the products. RESULTS: In total, 5,867 cases of antineoplastic agent-related AE reports were identified after excluding cases for duplication and cases assessed as 'unlikely' and 'unclassifiable', based on expert opinion. Of the patients with AEs, 52.4% were males and the median age was 56 years. In total, 460 AEs (7.8%) from 267 patients were reported as 'serious' AEs. The most common causative anti-cancer drug class was pyrimidine analogs (31.5%), followed by platinum compounds (19.9%), protein kinase inhibitors (10.8%), and taxanes (8.8%). The most common clinical manifestation of AEs was gastrointestinal toxicities (25.5%), followed by skin disorders (25.3%), and generalized reactions (14.3%). In total, 168 cases (2.9%) of unlabeled AEs were identified. Among these, 10 were reported as serious AEs. CONCLUSIONS: The most common causative class of antineoplastic agents was that of pyrimidine analogs. Gastrointestinal and dermatological toxicities were the most common clinical chemotherapy-related adverse events. Further investigation and monitoring to evaluate causality associated with unlabeled AEs identified in this analysis are needed.

Data Analysis for Anti-Neoplastic Chemotherapy-Related Adverse Events Reported to the Korean Pharmacovigilance Regional Network / 대한내과학회지

BACKGROUND/AIMS: To describe the toxicity profile of anti-neoplastic agents from real clinical settings, we analyzed spontaneously reported adverse events (AEs) using data from the adverse drug reaction (ADR) reporting system of the Korean Food and Drug Administration (KFDA). METHODS: Data were extracted from the nationwide spontaneous ADR reporting system of KFDA from July 2009 to December 2010. We extracted and analyzed data related to chemotherapy and identified unlabeled ADR that were not described in the package insert of the products. RESULTS: In total, 5,867 cases of antineoplastic agent-related AE reports were identified after excluding cases for duplication and cases assessed as 'unlikely' and 'unclassifiable', based on expert opinion. Of the patients with AEs, 52.4% were males and the median age was 56 years. In total, 460 AEs (7.8%) from 267 patients were reported as 'serious' AEs. The most common causative anti-cancer drug class was pyrimidine analogs (31.5%), followed by platinum compounds (19.9%), protein kinase inhibitors (10.8%), and taxanes (8.8%). The most common clinical manifestation of AEs was gastrointestinal toxicities (25.5%), followed by skin disorders (25.3%), and generalized reactions (14.3%). In total, 168 cases (2.9%) of unlabeled AEs were identified. Among these, 10 were reported as serious AEs. CONCLUSIONS: The most common causative class of antineoplastic agents was that of pyrimidine analogs. Gastrointestinal and dermatological toxicities were the most common clinical chemotherapy-related adverse events. Further investigation and monitoring to evaluate causality associated with unlabeled AEs identified in this analysis are needed.

Evolução do status de performance, índice de massa corpórea e distância percorrida no teste de caminhada de seis minutos em pacientes com câncer de pulmão avançado submetidos à quimioterapia / Evolution of performance status, body mass index, and six-minute walk distance in advanced lung cancer patients undergoing chemotherapy

OBJETIVO: Avaliar o efeito da quimioterapia sobre a condição física de pacientes com câncer de pulmão avançado. MÉTODOS: Foram avaliados 50 pacientes com câncer de pulmão não pequenas células nos estágios IIIB e IV e com status de performance segundo a escala do Eastern Cooperative Oncology Group (ECOG) entre zero e dois. Todos receberam quimioterapia com as drogas paclitaxel e derivados da platina e foram avaliados em três momentos (pré-quimioterapia, pós-quimioterapia e seis meses após o início do tratamento), nos quais a escala ECOG, o índice de massa corpórea (IMC) e a Distância percorrida no Teste de Caminhada de Seis minutos (DTC6) foram avaliados. RESULTADOS: Dos 50 pacientes incluídos, 14 foram a óbito, 5 foram excluídos do estudo por apresentar piora do status de performance, e 31 concluíram o seguimento de seis meses. Não houve diferença estatisticamente significativa para o IMC (p = 1,00, pré-quimioterapia vs. pós-quimioterapia; e p = 0,218, pré-quimioterapia vs. seis meses após) ou para a DTC6 entre os momentos de avaliação. O status de performance melhorou, principalmente com o aumento do número de pacientes assintomáticos após seis meses de acompanhamento (p = 0,031). CONCLUSÕES: O uso de quimioterapia teve um efeito benéfico no status de performance dos pacientes. Não houve alterações no IMC ou na DTC6 durante o período do estudo, o que pode sugerir a manutenção da condição física dos pacientes.

OBJECTIVE: To evaluate the effect of chemotherapy on the physical condition of patients with advanced lung cancer. METHODS: We evaluated 50 patients with non-small cell lung cancer (in stages IIIB and IV) and Eastern Cooperative Oncology Group (ECOG) performance status scale scores between zero and two. All patients underwent chemotherapy using paclitaxel and platinum derivatives and were evaluated at three time points (prechemotherapy, postchemotherapy and six months after starting the treatment), at which the ECOG scale, the body mass index (BMI) and the six-minute walk distance (6MWD) were assessed. RESULTS: Of the 50 patients included in the study, 14 died, 5 were excluded due to the worsening of their performance status, and 31 completed the six-month follow-up. There was no statistically significant difference between the time points of assessment for BMI (prechemotherapy vs. postchemotherapy, p = 1.00; and prechemotherapy vs. six months later, p = 0.218) or for 6MWD. Performance status improved, and this was especially due to the increase in the number of asymptomatic patients after the six-month follow-up (p = 0.031). CONCLUSIONS: Chemotherapy had a beneficial effect on the performance status of the patients. No significant changes in BMI or 6MWD were found during the study period, which might suggest the maintenance of the physical condition of the patients.

Evaluation of two-tier grading system and significance of p53 protein over-expression in ovarian serous carcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the two-tier MDACC grading system for ovarian serous carcinoma by comparing with the WHO grading system, and to investigate the role of p53 immunostaining in ovarian serous carcinoma grading.</p><p><b>METHODS</b>72 cases ovarian serous carcinoma of ovary were graded basing on the MDACC and WHO grading systems, respectively. Statistic analyses were made for the relationship between the data obtained from two grading systems and their clinical significance. All the cases were examined immunohistochemically by using antibody against p53 protein and the immunohistochemistry findings were analyzed with the two grading systems and clinical parameters.</p><p><b>RESULTS</b>There was a good correlation between the MDACC and WHO grading system (r=0.543, P=0.000). Neither system has a definite relationship with the disease-free survival time (P=0.170 vs. P=0.075), cytoreduction (P=0.478 vs. P=0.120), and the curative effect of platinum-based chemotherapy (P=0.418 vs. P=0.403). However, compared with the WHO grading system, MDACC grading system has a better correlation with tumor stage (P=0.041 vs. P=0.002), 3-year disease-free survival rate (P=0.077 vs. P=0.004), overall survival time (P=0.080 vs. P=0.046), and p53 immunohistochemistry results (P=0.334 vs. P=0.035). No significant difference was found between p53 immunohistochemistry results with other clinical characteristics and prognostic factors.</p><p><b>CONCLUSIONS</b>Compared with the WHO system, the MDACC system showed a better prognostic value and was more likely correlated with the novel dualistic model for ovarian serous carcinogenesis. Although p53 immunostaining was valuable in assisting MDACC grading, it should be cautious to use it alone as an independent indicator in predicting the prognosis of ovarian serous carcinoma.</p>

Platinum tetrachloride coupled PEG-PEI as drug carrier and gene delivery vector / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To construct a drug carrier and gene vector PEG-PEI-Pt.</p><p><b>METHODS</b>Polyethyleneglycol (PEG) was coupled to polyethylenimine (PEI 600) and platinum tetrachloride; PEG-PEI-Pt complex was formed in ethanol. The complex was characterized by XRD, UV-VIS and FT-IR and the DNA condensation was tested by electrophoretic mobility shift assay. The cell viability was evaluated by MTT assay in Hela, B16, A293 and COS-7 cells and in vitro transfection efficiency was measured in A293 and B16 cells.</p><p><b>RESULT</b>The structure of PEG-PEI-Pt was characterized by XRD, UV-VIS and FT-IR. PEG-PEI-Pt complex was able to bind DNA at N/P weight ratio of 0.4:1; the complex showed cytotoxicity on Hela and B16 cells. The complex had higher transfection efficiency in A293 and B16 cells than PEI 600.</p><p><b>CONCLUSION</b>A novel drug carrier and gene vector PEG-PEI-Pt was constructed successfully.</p>

Análise de sobrevida e tolerabilidade à quimioterapia baseada em compostos platínicos em pacientes portadores de câncer de pulmão de células não-pequenas com idade superior a 70 anos / Analysis of survival and tolerability of chemotherapy based on platinum compounds in patients with lung cancer non-small cell older than 70 years

Avaliar se o envelhecimento compromete a sobrevida e exacerba a toxicidade dos pacientes portadores de carcinoma de pulmão, doença avançada em compostos platínicos...

Phase II study of gemcitabine combined with platinum chemotherapy for recurrent epithelial ovarian cancer / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the anti-tumor effect and toxicity of gemcitabine combined with platinum chemotherapy on recurrent epithelial ovarian cancer.</p><p><b>METHODS</b>Phase II study of gemcitabine combined with platinum chemotherapy was carried out in 22 patients with recurrent epithelial ovarian cancer. Median age of patients was 50.5 years old. Seven patients were platinum-sensitive and 15 patients were platinum-resistant or -refractory. All patients received gemcitabine combined with carboplatin or oxaliplatin chemotherapy. Patients' response rate (RR) and toxicity of gemcitabine combined with platinum chemotherapy were evaluated.</p><p><b>RESULTS</b>A total of 98 gemcitabine-based chemotherapy cycles were performed. Total RR was 36.4%, RR of platinum-sensitive patients was 4/7 and platinum-resistant and -refractory patients was 4/15. The estimated median survival time was 10.0 months (95% CI: 7.0-13.0) after initiation of gemcitabine combined with platinum chemotherapy. There was no significant difference in survival time between platinum-resistant/refractory group and platinum-sensitive group (P = 0.061). Side effects of gemcitabine combined with platinum chemotherapy were observed in 81.8% of patients. Grade II/III anemia (54.5%) and grade III/IV neutropenia (54.5%) were most common toxicities. Ten (45.5%) patients had to delay their chemotherapy cycles or reduce the dose of chemotherapeutic drugs because of the severe side effects. Fourteen (63.6%) patients received granulocyte colony-stimulating factor to relieve neutropenia, and 8 (36.4%) patients received component blood transfusion to treat anemia or thrombocytopenia. There was no treat-ment-associated death.</p><p><b>CONCLUSION</b>Gemcitabine combined with platinum chemotherapy appears to be an effective and well-tolerant treatment for recurrent epithelial ovarian cancer, including platinum-resistant or -refractory diseases.</p>

Evaluation of apoptosis-induction by newly synthesized phthalazine derivatives in breast cancer cell lines.

Newly synthesized phthalazine derivatives including copper and platinum complexes were evaluated for cytotoxicity in human breast cancer cell lines. The cells were incubated with the compounds (100 microM) for 72 h and cytotoxicity, apoptosis and DNA content were measured by flow cytometery. Our results suggest that the parent (H1-2), copper (C1-2)- and platinum (P1-2)-derivatized compounds were relatively more active in inducing apoptosis and cell killing in both human breast cancer cell lines, MDA-MB-231 cells being the more sensitive. Other compounds showed weak or no response towards these parameters except H-5 causing 40% apoptosis in MDA-MB-231 cells. Addition of copper or platinum in the structures generally reduced the apoptotic potential. Possible roles for structure activity relationships are discussed.

Efficacy of platinum plus cyclophosphamide in patients with epithelial ovarian cancer.

OBJECTIVES: To determine the response rate (RR), 5-year progression-free survival (PFS), and the 5-year survival rate (SVR) of epithelial ovarian cancer patients who received platinum plus cyclophosphamide as adjuvant postoperative chemotherapy. MATERIAL AND METHOD: Epithelial ovarian cancer patients who underwent tumor debulking surgery and received platinum plus cyclophosphamide as adjuvant chemotherapy at Vajira Hospital from January 1995 to December 2003 were identified. All clinical and pathological data were reviewed RESULTS: Among 114 patients included in the present study, 101 patients were evaluable for response. Overall response rate was 79.2%. The 5-year PFS and 5-year SVR were 60.3% (95% confidence interval [95% CI]; 50.5, 70.1%) and 60.7% (95% CI; 50.9, 70.5%) respectively. Subgroup analysis showed better RR, PFS, and SVR in early stage than advanced stage disease. CONCLUSION: The overall RR, 5-year PFS, and 5-year SVR of patients of the whole group were modest. These outcomes were significantly better in the early stage than the advanced stage.

Symmetry properties of tetraammine platinum(II) with C2v and C4v point groups / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Let G be a weighted graph with adjacency matrix A=[a(ij)]. An Euclidean graph associated with a molecule is defined by a weighted graph with adjacency matrix D=[d(ij)], where for i not = j, d(ij) is the Euclidean distance between the nuclei i and j. In this matrix d(ii) can be taken as zero if all the nuclei are equivalent. Otherwise, one may introduce different weights for different nuclei. Balasubramanian (1995) computed the Euclidean graphs and their automorphism groups for benzene, eclipsed and staggered forms of ethane and eclipsed and staggered forms of ferrocene. This paper describes a simple method, by means of which it is possible to calculate the automorphism group of weighted graphs. We apply this method to compute the symmetry of tetraammine platinum(II) with C2v and C4v point groups.

A Phase II Trial of Haptaplatin/5-FU and Leucovorin for Advanced Stomach Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Heptaplatin (SKI-2053 R) is a new platinum analogue, with a better toxicity profile than cisplatin, and has antitumor activity even in cisplatin resistant cell lines. 5-fluoruracil (5-FU) has shown synergy with platinum compounds. This phase II trial was designed to determine the efficacy and toxicities of heptaplatin/ 5-FU (5-fluorouracil) for treating stomach cancer. MATERIALS AND METHODS: Thirty-two patients with advanced, measurable gastric adenocarcinomas were enrolled in this trial. The treatment consisted of heptaplatin, 400 mg/m2/day (1 hour IV infusion), on day 1 and 5-FU, 800 mg/m2/day (12 hours IV infusion), on days 1 to 5. The cycles were repeated every 3 weeks. RESULTS: Of the 26 evaluable patients, 9 had partial responses and 1a complete response (overall response rate, 38%; 95% confidence interval, 19~57%). The median response duration was 23 weeks (range: 4~60 weeks). The median time to progression was 26 weeks (range: 3~68 weeks). The grades III-IV toxicities were mostly hematological toxicities: leucopenia was observed in 11 patients (35%) and thrombocytopenia 4 (13%). No definite neuropathy was observed. Grade I-II nephropathy was also noted: grade I high BUN/creatinine levels occurred in 5 patients (16%), grade II proteinuria 2 (6%), grade I proteinuria 5 (16%). Neutropenic fever developed in 5 patients (16%) and 1 died of pneumonia in a neutropenic state. CONCLUSION: This study suggests that the regimen of Heptaplatin/5-FU should be effective and have a favorable toxicity profile for the patients suffering with advanced stomach cancer.