Citations

Purpose Epothilones are a new class of nontaxane tubulin polymerization agents that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a semisynthetic analog of the natural product epothilone B. This study was performed to determine the activity of BMS-247550 in patients with soft tissue sarcomas (STSs) who had not received prior chemotherapy for metastatic disease. Patients and Methods Patients with measurable, advanced, or metastatic STS with no prior chemotherapy for metastatic disease were treated with BMS-2457550 50 mg/m 2 intravenously during 1 hour every 21 days. All responses were confirmed 4 weeks later. Results Thirty-one patients (median age, 54 years; range, 19 to 78 years; 48% female) were entered onto the trial and were assessable for response. All but one patient had an Eastern Cooperative Oncology Group performance score of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was 22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression-free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic, with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31 patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4 nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue (10%). Conclusion BMS-247550 has limited activity against STSs when given in this dose and schedule. The clinical toxicity is similar to that of taxanes.

ABSTRACT OBJECTIVE To determine local control (LC) and complication rates for patients with intracranial meningiomas who underwent radiosurgery. METHODS One hundred ninety consecutive patients with 206 meningiomas underwent radiosurgery between 1990 and 1998. One hundred forty-seven tumors (77%) involved the cranial base. The median age at the time of radiosurgery was 58 years (range, 20–90 yr). There were 126 female patients (66%). One hundred twelve patients (59%) had undergone one or more previous operations (median, 1; range, 1–5). Twenty-two patients (12%) had either atypical (n = 13) or malignant (n = 9) tumors. The median prescription isodose volume was 8.2 cm3 (range, 0.5–50.5 cm3), and the median tumor margin dose was 16 Gy (range, 12–36 Gy). The median imaging and clinical follow-up periods were 40 and 47 months, respectively. RESULTS Overall survival rates for the entire cohort at 5 and 7 years were 82 and 82%, respectively; cause-specific survival rates at 5 and 7 years were 94 and 92%, respectively. The cause-specific survival rates at 5 years for patients with benign, atypical, and malignant tumors were 100, 76, and 0%, respectively (P < 0.0001). The 5-year LC rate was 89%, with 114 tumors (56%) decreasing in size. LC rates were correlated with tumor histological features (P < 0.0001); patients with benign tumors exhibited a 5-year LC rate of 93%, compared with 68 and 0% for patients with atypical or malignant meningiomas, respectively. No correlation was observed between radiation dose and LC rate. Twenty-four patients (13%) experienced treatment-related complications, including cranial nerve deficits (8%), symptomatic parenchymal changes (3%), internal carotid artery stenosis (1%), and symptomatic cyst formation (1%). Only six patients (3%) exhibited decreases in functional status that were directly related to radiosurgery. Tumor volume, tumor margin dose, or previous radiotherapy was not associated with the development of radiation-related complications. CONCLUSION Radiosurgery is an effective management strategy for many patients with meningiomas. Patients with atypical or malignant tumors exhibit high recurrence rates despite the use of radiosurgery, and these patients continue to exhibit worse cause-specific survival rates despite aggressive treatment, including surgery, external-beam radiotherapy, and radiosurgery. Further study is needed to determine the tumor control and complication rates 10 years or more after meningioma radiosurgery.

Background Aprotinin and tranexamic acid are routinely used to reduce bleeding in cardiac surgery. There is a large difference in agent price and perhaps in efficacy. Methods In a prospective, randomized, partially blinded study, 168 cardiac surgery patients at high risk for bleeding received either a full-dose aprotinin infusion, tranexamic acid (10-mg/kg load, 1-mg x kg(-1) x h(-1) infusion), tranexamic acid with pre-cardiopulmonary bypass autologous whole-blood collection (12.5% blood volume) and reinfusion after cardiopulmonary bypass (combined therapy), or saline infusion (placebo group). Results There were complete data in 160 patients. The aprotinin (n = 40) and combined therapy (n = 32) groups (data are median [range]) had similar reductions in blood loss in the first 4 h in the intensive care unit (225 [40-761] and 163 [25-760] ml, respectively; P = 0.014), erythrocyte transfusion requirements in the first 24 h in the intensive care unit (0 [0-3] and 0 [0-3] U, respectively; P = 0.004), and durations of time from end of cardiopulmonary bypass to discharge from the operating room (92 [57-215] and 94 [37, 186] min, respectively; P = 0.01) compared with the placebo group (n = 43). Ten patients in the combined therapy group (30.3%) required transfusion of the autologous blood during cardiopulmonary bypass for anemia. Conclusions The combination therapy of tranexamic acid and intraoperative autologous blood collection provided similar reduction in blood loss and transfusion requirements as aprotinin. Cost analyses revealed that combined therapy and tranexamic acid therapy were the least costly therapies.

ABSTRACT We compared the performance characteristics of a real-time PCR method, the LightCycler Strep-A assay (Roche Applied Science, Indianapolis, Ind.), to those of a rapid antigen immunoassay, the Directigen 1-2-3 Group A Strep Test kit (BD Diagnostic Systems, Sparks, Md.), and a standard culture method for detection of group A streptococci (GAS) from 384 throat swabs. The LightCycler PCR produced more positive results ( n = 58) than either culture ( n = 55) or the Directigen immunoassay ( n = 31). The results of the LightCycler PCR and the Directigen method were independently compared to the results of the accepted “gold standard,” bacterial culture. The sensitivities, specificities, and positive and negative predictive values for this comparison were as follows: for the Directigen method, 55, 99, 97, and 93%, respectively; for the LightCycler PCR, 93, 98, 88, and 99%, respectively. In no case was a throat swab positive by both the LightCycler PCR and the Directigen method but negative by culture. The medical histories of patients whose throat swabs were negative by culture but positive by either the LightCycler PCR ( n = 7) or the Directigen method ( n = 1) were reviewed. All of these patients had signs or symptoms compatible with GAS disease, and therefore, all of these discordant positive results (along with positive results by either the Directigen method or the LightCycler PCR that agreed with the culture results) were counted as true positives for statistical analysis. For this analysis, the LightCycler PCR detected more true-positive results than the culture method (58 versus 55 swabs); however, this difference was not statistically significant ( P = 0.5465). In contrast, statistically significantly more true-positive results occurred by culture than by the Directigen method (55 versus 31 swabs; P < 0.0001) and by the LightCycler PCR than by the Directigen method (58 versus 31 swabs; P < 0.0001). The LightCycler PCR is a suitable stand-alone method for the detection of GAS from throat swabs. Additionally, this method requires less than half the personnel time and the procedure can be completed in considerably less time (∼1 h) than our standard approach (up to 2 days) for detection of GAS in throat swabs (i.e., testing by the Directigen method with negative results verified by culture).