Discrepancy in calculated and measured glomerular filtration rates in patients treated with PARP inhibitors.

OBJECTIVE: To describe discrepancies in calculated and measured glomerular filtration rate in patients using PARP (poly ADP ribose polymerase) inhibitors who had an elevation in serum creatinine levels. METHODS: Retrospective cohort, single center study. Patients included were those with ovarian or endometrial cancer taking olaparib, rucaparib or niraparib, and in in whom an increased serum creatinine was identified. The study cohort included those who also underwent technetium-99m radioisotope renography (glomerular filtration rate (GFR) scan). The main objective is to describe the discrepancies in calculated glomerular filtration rate using the Cockcroft-Gault method and measured glomerular filtration rate using a GFR scan. RESULTS: 211 patients were included in the study; 64 (30%) had on-treatment elevated serum creatinine, and 23 (36%) underwent a GFR scan. 32 GFR scans were performed (six patients had more than one scan). Using a clinical cut-off ≥50 mL/min as normal renal function, both calculated and estimated glomerular filtration rates were below normal in 6 of 32 GFR scans. In those patients undergoing a GFR scan, serum creatinine had risen a median 49% (IQR 20-66%, range 0-144%) above baseline. Discordance between a calculated low glomerular filtration rate and an estimated normal glomerular filtration rate occurred in 63% (range of glomerular filtration rate discrepancy: -46% to +237%). Despite increases in serum creatinine on therapy and a subsequent significant decline in the per patient calculated creatinine clearance (mean 65.6 mL/min vs 43.4 mL/min; p<0.0001), the estimated glomerular filtration rate from the renal scan was nearly identical to the patient's baseline (65.6 mL/min vs 66.1 mL/min; p=0.89). CONCLUSIONS: Serum creatinine elevation in patients taking PARP inhibitors may not be associated with a true decrease in glomerular filtration rate. A high index of suspicion should be maintained for alternative causes of elevated serum creatinine in patients treated with PARP inhibitors who lack other sources of renal injury.

Risk of fatigue and anemia in patients with advanced cancer treated with olaparib: A meta-analysis of randomized controlled trials.

INTRODUCTION: PARP inhibitors are a new class of drugs that are currently being studied in several malignancies. Olaparib is FDA-approved for advanced breast cancer and advanced ovarian cancer patients. Fatigue and anemia are among the most common cancer and treatment-related symptoms. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) to characterize the incidence and relative risks (RRs) of fatigue and anemia associated with olaparib. METHODS: PubMed, Cohrane, Embase and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018. The eligible studies were phase II and III RCT of olaparib. Safety profile from each selected study was evaluated for all-grade and high-grade fatigue and anemia adverse events. Summary incidences and the RR, with 95% confidence intervals, of all-grade and high-grade events were calculated using random-effects or fixed-effects model based on the heterogeneity of selected studies. RESULTS: A total of 9 trials were selected, and included 2074 patients with advanced ovarian, gastric, prostate, lung or breast cancer. 908 patients received placebo/control treatments and 1166 received olaparib alone or combination with other active cancer treatments. The RR of all-grade and high fatigue was 1.24 (95% CI, 1.10-1.39) and 1.71 (95% CI, 1.06-2.77), respectively. The RR of all-grade and high-grade anemia was 2.10 (95% CI, 1.48-2.98) and 3.15 (95% CI, 1.73-5.71), respectively. CONCLUSION: Our findings suggest that the olaparib treatment is associated with an increased risk of fatigue and anemia. Since fatigue and anemia are very common treatment related adverse events, and both can impair the quality of life of patients, it is important to identify them early and manage it accordingly in order to optimize the overall treatment.

Sensibilização a aeroalérgenos em adultos jovens vivendo na região sul do Brasil / Sensitization to aeroallergens among young adults living in southern Brazil

Objetivo: Estudos epidemiológicos sobre rinite foram realizados em crianças e adolescentes,entretanto a população adulta tem sido pouco avaliada, uma vez que o protocolo International Study of Asthma and Allergies in Childhood (ISAAC) não foi validado para essa faixa etária. O objetivo do presente trabalho foi determinar a frequência de rinite e de sensibilização a aeroalérgenosem adultos jovens. Métodos: Estudo de série, com participação de 236 estudantes de Medicina,com idades entre 16 e 32 anos, que preencheram o questionário ISAAC módulo Rinite. Subgrupode indivíduos que relataram sintomas de rinite no questionário ISAAC foi submetido a testes cutâneos de hipersensibilidade imediata (prick test), com extratos de ácaros da poeira domiciliare polens de gramíneas. Resultados: A idade média dos participantes foi de 21,4 anos (±2,4).Cento e setenta e um estudantes (72,5%) relataram sintomas de rinite, e 156 destes (91,2%)apresentaram sintomas nos últimos 12 meses. Cento e dezesseis indivíduos (67,8%) relataram lacrimejamento e prurido ocular associados. Rinite foi mais frequente no sexo feminino (62,2%).Dos 63 indivíduos que realizaram prick-test, 79% tiveram teste positivo para algum alérgeno, sendo a maioria (88%) positiva tanto para ácaros quanto para polens. Houve associação entre ocorrência de sintomas de rinite nos meses de janeiro, fevereiro, setembro, outubro, novembro e dezembro e testes cutâneos positivos para azevém (p < 0,05). Conclusão: A alta frequência derinite sugere a necessidade de ações conjuntas da saúde ambiental e da saúde coletiva, visando à diminuição da exposição a alérgenos ambientais derivados de polens e ácaros.

Objective: Epidemiological studies on rhinitis have been conducted with children and adolescents,but fewer studies have assessed adults, as the International Study of Asthma and Allergies inChildhood (ISAAC) protocol has not been validated for this age group. The aim of the present studywas to determine the frequency of rhinitis and sensitization to aeroallergens in young adults.Methods: This series study comprised 236 medical students aged between 16 and 32 years whoanswered the Rhinitis module of the ISAAC questionnaire. Individuals reporting rhinitis symptomson the ISAAC questionnaire underwent skin prick testing with house dust mite and grass pollenextracts. Results: The mean age of participants was 21.4 years (± 2.4). One hundred seventy onestudents (72.4%) reported symptoms of rhinitis, and 156 of those (91.2%) presented symptomsin the past 12 months. One hundred and sixteen individuals (67.8%) reported associated tearingand eye itching. Rhinitis was more frequent in females (62.2%). Among the 63 subjects whounderwent skin prick testing, 79% had a positive result for at least one allergen, and the majority(88%) resulted positive for both mite and pollen extracts. There was a significant associationbetween rhinitis symptoms in the months of January, February, September, October, November,and December and positive skin tests for rye grass (p < 0.05). Conclusion: The high frequency ofrhinitis found in our study suggests the need for joint actions by environmental and public healthagencies, aimed at reducing exposure to environmental pollen and mite allergens.