RESUMO
BACKGROUND: Erlotinib is a standard first-line therapy for patients who have metastatic nonsmall cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The recommended dose of 150 mg daily is the maximum tolerated dose (MTD). Few clinical data are available regarding its efficacy at doses less than the MTD. METHODS: An institutional database was queried for patients with advanced NSCLC who were positive for EGFR L858R mutations or exon 19 deletions and had received treatment with erlotinib. The treatment course, including the erlotinib dose at initiation of treatment, at 4 months into therapy, and at disease progression, was retrospectively studied. Progression-free survival (PFS) was compared between patients who received the MTD (150 mg) and those who received reduced-dose erlotinib (≤100 mg). RESULTS: In total, 198 eligible patients were identified. Thirty-one patients (16%) were initiated on reduced-dose erlotinib; they were older (P = .001) and had lower performance status (P = .01) compared with those who were initiated on erlotinib at the MTD. The response rate to reduced-dose erlotinib was 77%. The median PFS of patients initiated on reduced-dose erlotinib was 9.6 months versus 11.4 months for those initiated at the MTD, a difference that was not statistically significant (hazard ratio, 0.81; 95% confidence interval, 0.54-1.21; P = .30). There was a nonsignificant trend toward higher rates of progression within the central nervous system with reduced-dose erlotinib. CONCLUSIONS: At doses below the MTD, erlotinib treatment results in a high response rate and a prolonged median PFS. Review of the literature indicates that 15 of 30 small-molecule inhibitors that are approved or in late-stage development for cancer therapy have recommended doses below the MTD. When the toxicities of MTD dosing are a concern, an investigation of small-molecule inhibitors at doses below the MTD is warranted. Cancer 2016;122:3456-63. © 2016 American Cancer Society.
RESUMO
BACKGROUND: Bispectral Index (BIS) derived from electroencephalogram (EEG) is primarily developed to monitor the depth of unconsciousness. Recent evidence suggests that BIS may also help in the detection of cerebral ischemia and prognostication of outcome of traumatic brain injury (TBI). The present study was designed to investigate the correlation between Glasgow Coma Score (GCS) and BIS in mild and moderate head injury. METHODS: In 29 patients with mild (GCS 13-15) and moderate (GCS 9-12) head injuries who underwent craniotomy, GCS and BIS were measured before surgery, after surgery and once a day for the first 10 days. RESULTS: A significant correlation was found between GCS and BIS in the data sets from all the patients (r = 0.67; p < 0.001). Mean BIS values increased with increasing GCS scores. However, the scatter of BIS values for any GCS score was high limiting the value of BIS in predicting GCS. Mean BIS values were significantly different between mild and moderate head injuries [65.7 +/- 16.1 vs. 85.7 +/- 6.1, p = 0.006]. CONCLUSION: In patients with mild and moderate head injury, significant correlation exists between GCS and BIS. But the high degree of scatter of BIS values for any given GCS score limits its use as a monitor of depth of coma in TBI. Further studies are required to understand the relation between BIS algorithm and cerebral electrical activity following TBI to define the role of BIS as an electrophysiological correlate of consciousness in TBI.