Phase I trial of erlotinib combined with cisplatin and radiotherapy for patients with locally advanced cervical squamous cell cancer.

PURPOSE: This phase I trial was aimed to determine the maximum tolerated dose and related toxicity of erlotinib (E) when administered concurrently with standard chemoradiation (CRT) for cervical cancer. EXPERIMENTAL DESIGN: In a modified Fibonacci design, the study aimed to study three cohorts of at least three patients receiving escalating doses of erlotinib (50/100/150 mg) combined with cisplatin (40 mg/m(2), weekly, 5 cycles) and radiotherapy (external beam 4,500 cGy in 25 fractions, followed by 4 fractions/600 cGy/weekly of brachytherapy) in squamous cell cervical carcinoma patients, stage IIB to IIIB. RESULTS: Fifteen patients were enrolled, 3 at dose level (DL) 50 mg, 4 at DL 100 mg, and 8 at DL 150 mg. Patients presented median age 47 (36-59), stage IIB (46.2%) and IIIB (53.8%). Overall, E+CRT was well-tolerated. Three patients did not complete the planned schedule. One patient at DL 100 mg withdrew informed consent due to grade 2 rash; at DL 150 mg, 1 patient presented Raynaud's Syndrome and had C interrupted, and another patient presented grade 4 hepatotoxicity. The latter was interpreted as dose limiting toxicity and a new cohort of 150 mg was started. No further grade 4 toxicity occurred. Grade 3 toxicity occurred in 6 cases: diarrhea in 3 patients, rash in 2 patients, and leukopenia in 1 patient. E+CRT did not lead to limiting in-field toxicity. CONCLUSIONS: E+CRT is feasible to locally advanced squamous cell cervical cancer and is well tolerated. The maximum tolerated dose has been defined as 150 mg. To the best of our knowledge, this is the first report of a combination of erlotinib, cisplatin, and pelvic radiotherapy.

Association of frailty with short-term outcomes, organ support and resource use in critically ill patients.

PURPOSE: Frail patients are known to experience poor outcomes. Nevertheless, we know less about how frailty manifests itself in patients' physiology during critical illness and how it affects resource use in intensive care units (ICU). We aimed to assess the association of frailty with short-term outcomes and organ support used by critically ill patients. METHODS: Retrospective analysis of prospective collected data from 93 ICUs in Brazil from 2014 to 2015. We assessed frailty using the modified frailty index (MFI). The primary outcome was in-hospital mortality. Secondary outcomes were discharge home without need for nursing care, ICU and hospital length of stay (LOS), and utilization of ICU organ support and transfusion. We used mixed logistic regression and competing risk models accounting for relevant confounders in outcome analyses. RESULTS: The analysis consisted of 129,680 eligible patients. There were 40,779 (31.4%) non-frail (MFI = 0), 64,407 (49.7%) pre-frail (MFI = 1-2) and 24,494 (18.9%) frail (MFI ≥ 3) patients. After adjusted analysis, frailty was associated with higher in-hospital mortality (OR 2.42, 95% CI 1.89-3.08), particularly in patients admitted with lower SOFA scores. Frail patients were less likely to be discharged home (OR 0.36, 95% CI 0.54-0.79) and had higher hospital and ICU LOS than non-frail patients. Use of all forms of organ support (mechanical ventilation, non-invasive ventilation, vasopressors, dialysis and transfusions) were more common in frail patients and increased as MFI increased. CONCLUSIONS: Frailty, as assessed by MFI, was associated with several patient-centered endpoints including not only survival, but also ICU LOS and organ support.

The effects of performance status one week before hospital admission on the outcomes of critically ill patients.

PURPOSE: To assess the impact of performance status (PS) impairment 1 week before hospital admission on the outcomes in patients admitted to intensive care units (ICU). METHODS: Retrospective cohort study in 59,693 patients (medical admissions, 67 %) admitted to 78 ICUs during 2013. We classified PS impairment according to the Eastern Cooperative Oncology Group (ECOG) scale in absent/minor (PS = 0-1), moderate (PS = 2) or severe (PS = 3-4). We used univariate and multivariate logistic regression analyses to investigate the association between PS impairment and hospital mortality. RESULTS: PS impairment was moderate in 17.3 % and severe in 6.9 % of patients. The hospital mortality was 14.4 %. Overall, the worse the PS, the higher the ICU and hospital mortality and length of stay. In addition, patients with worse PS were less frequently discharged home. PS impairment was associated with worse outcomes in all SAPS 3, Charlson Comorbidity Index and age quartiles as well as according to the admission type. Adjusting for other relevant clinical characteristics, PS impairment was associated with higher hospital mortality (odds-ratio (OR) = 1.96 (95 % CI 1.63-2.35), for moderate and OR = 4.22 (3.32-5.35), for severe impairment). The effects of PS on the outcome were particularly relevant in the medium range of severity-of-illness. These results were consistent in the subgroup analyses. However, adding PS impairment to the SAPS 3 score improved only slightly its discriminative capability. CONCLUSION: PS impairment was associated with worse outcomes independently of other markers of chronic health status, particularly for patients in the medium range of severity of illness.