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.

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

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.

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...

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.