ABSTRACT
INTRODUCTION: Concurrent chemotherapy and radiotherapy is recommended for the treatment of locally advanced unresectable head and neck (H&N) cancer. OBJECTIVE: The primary purpose of the Phase I part of the study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose (RD) of docetaxel with hyperfractionation radiotherapy. The primary objective of the Phase II part was to determine the response rate to the RD of treatment and, secondarily, to assess the toxicity of the schedule, time to progression, duration of response and overall survival (OS). MATERIALS AND METHODS: Patients (n=9 in Phase I; n=19 in Phase II) had unresectable H&N cancer. The starting docetaxel dose was 20 mg/m(2) plus hyperfractionated radiotherapy. Ramping of docetaxel was 5 mg/m(2) if MTD was not reached. RESULTS: MTD of docetaxel was 20 mg/m(2). Limiting toxicities were grade 4 pneumonia and grade 4 mucositis. The RD was 15 mg/m(2). Phase II initial response was 76% (CR=18%; PR=9%); updated response was 89% (CR=59%; PR=29%). The median progression-free survival was 7.8 months (95%CI: 0-22.3) and the median OS was 15.1 months (95%CI: 0-35.9). Grade 3-4 toxicities included mucositis (91%), pneumonia (27%) and fatigue (27%). There were 5 toxic deaths (2 from intestinal perforation, 3 from pneumonia). CONCLUSIONS: Weekly docetaxel+hyperfractionation radiotherapy is active but with high toxicity rates and, hence, this treatment regimen would be difficult to justify.
Subject(s)
Antineoplastic Agents/therapeutic use , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Taxoids/therapeutic use , Adult , Aged , Combined Modality Therapy/adverse effects , Docetaxel , Dose Fractionation, Radiation , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Female , Head and Neck Neoplasms/pathology , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Staging , Radiotherapy/adverse effectsABSTRACT
OBJECTIVE: To evaluate whether critically ill patients with systemic inflammatory response syndrome, on admission to an intensive care unit, had more severe oxidative stress than those without this syndrome. DESIGN: A prospective, cohort study. SETTING: A mixed medical and surgical adult intensive care unit with 12 beds. PATIENTS: A total of 68 consecutive patients admitted to the intensive care unit. INTERVENTIONS: Venous blood samples were routinely obtained within 24 hrs of admission. MEASUREMENTS AND MAIN RESULTS: Patients' plasma total antioxidant capacity, the lipid peroxidation products malondialdehyde and 4-hydroxynonenal, reduced sulfhydryl groups, and nitrites/nitrates were measured by spectrophotometric technique at admission to the intensive care unit. Myeloperoxidase (enzyme-linked immunosorbent assay) and polymorphonuclear elastase (immuno-activation assay) were also measured on admission to the intensive care unit. The patients with criteria of systemic inflammatory response syndrome (n = 20) had higher Acute Physiology and Chronic health Evaluation III scores (determined by collecting the worst value within 24 hrs after admission to the intensive care unit) and plasma concentrations of lipid peroxidation products and nitrites/nitrates and lower plasma concentration of reduced sulfhydryl groups and plasma total antioxidant capacity than patients without the syndrome (n = 48). Moreover, the markers for leukocyte activation, myeloperoxidase and polymorphonuclear elastase, presented higher concentrations in the plasma of patients with systemic inflammatory response syndrome. CONCLUSIONS: Patients admitted to the intensive care unit with criteria of systemic inflammatory response syndrome had a more severe oxidative stress than patients without this syndrome.
