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Background: Southwest Oncology Group 0124 was a large North American phase 3 trial that failed to confirm a survival benefit for cisplatin/irinotecan over cisplatin/etoposide in patients with extensive stage small cell lung cancer (SCLC). These results were contrary to Japan Clinical Oncology Group 9511, a phase 3 trial exclusively in Japanese patients. Because 0124 and 9511 used identical treatment regimens and similar eligibility criteria, patient-level data were pooled from both trials, and a common arm analysis was performed to explore potential reasons for the divergent results.Methods: Patients with documented extensive stage SCLC and adequate end-organ function were randomized to intravenously receive either cisplatin 60 mg/m(2) Day 1 + irinotecan 60 mg/m(2) Days 1, 8, and 15 every 4 weeks or cisplatin 80 mg/m(2) Day 1 + etoposide 100 mg/m(2) Days 1-3 every 3 weeks. Demographic and outcome data were compared among 805 patients enrolled in 9511 and 0124 receiving identical treatment using a logistic model adjusted for age, sex, and performance status (PS).Results: Of 671 patients in 0124, 651 eligible patients were included, as were all 154 patients from 9511. Significant differences in sex and PS distribution as well as toxicity were seen between trials. There were also significant differences in response rates (87% vs 60%, P<.001) and median overall survival (12.8 vs 9.8 months, P<.001) when the cisplatin/irinotecan arms from both trials were compared.Conclusions: Significant differences in patient demographics, toxicity, and efficacy were identified in the 9511 and 0124 populations. These results, relevant in the current era of clinical trials globalization, warrant: 1) consideration of differential patient characteristics and outcomes among populations receiving identical therapy; 2) utilization of the common arm model in prospective trials; and 3) inclusion of pharmacogenomic correlates in cancer trials where ethnic/racial differences in drug disposition are expected. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study was undertaken to determine the relationship of umbilical cord pH and base excess (BE) values to adverse neonatal outcomes for a large tertiary hospital population delivering at term.Study design The perinatal/neonatal database of St. Joseph's Health Care, London, Canada, was used to obtain the umbilical cord pH and BE values, incidence of adverse neonatal outcomes, and patient demographics for all term (>/=37 weeks' gestation), singleton, liveborn infants with no major anomalies delivering between November 1995 and March 2002 (n=20,456). Statistical analyses included chi(2) analysis, logistic regression models to develop odds ratios and creation of receiver operating characteristic (ROC) curves with area under curve (AUC) calculations. RESULTS: Umbilical vein and artery pH and BE values for this tertiary care population averaged 7.33 +/- 0.06 and 7.24 +/- 0.07, and -4.5 +/- 2.4 and -5.6 +/- 3.0 mmol/L, respectively. Apgar less than 7 at 5 minutes, neonatal intensive care unit (NICU) admission, and assisted neonatal ventilation had significant inverse relationships with both umbilical artery and umbilical vein pH and BE (all P < .0001), with marginal increases in the incidences of these outcomes beginning with cord blood values close to the mean, and more substantial increases with cord values less than 1 or 2 SD below the mean, depending on the outcome studied. The ROC AUC for all these relationships were significant (P < .001) ranging from 0.76 to 0.79 when predicting Apgar less than 7 at 5 minutes to 0.68 to 0.70 when predicting NICU admission, and with cutoff cord blood values at which sensitivity and specificity were maximized again close to mean values. For each of these neonatal outcomes, the relation to cord blood values was similar with little difference in the data analysis whether using pH or BE values, and whether from the umbilical artery or vein. CONCLUSION: There is a progression of risk in term infants for Apgar less than 7 at 5 minutes, NICU admission, and need for assisted ventilation with worsening acidosis at birth, which begins with cord blood values close to mean values indicating a higher threshold for associated acidemia with these outcomes than is seen for more severe neonatal outcomes. Copyright © 2004 by Elsevier Science (USA). [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to determine the relationship/predictive value of umbilical cord pH and base excess (BE) values to adverse neonatal outcomes for preterm infants.Study Design: A tertiary center perinatal/neonatal database was used to obtain umbilical cord pH and BE values, adverse neonatal outcomes, and patient demographics for preterm (PT, 32-36 weeks gestational age) and very preterm (VPT, 25-32 weeks gestational age) singleton live-born infants delivered between November 1995 and March 2002.Results: PT (n=1807) and VPT (n=603) groups demonstrated a significant inverse curvilinear relationship of umbilical cord pH and BE values to Apgar score <7 at 5 minutes, respiratory distress syndrome, assisted ventilation, and intraventricular hemorrhage/periventricular leukomalacia. Receiver operating characteristic area under the curve values ranged from 0.69 to 0.86 (PT) and 0.70 to 0.87 (VPT). There was little difference between umbilical vein, umbilical artery, pH, or BE in predictive value.Conclusion: Umbilical cord pH and BE are related to subsequent adverse outcome events for infants delivered preterm. Worsening acidosis is associated with progressively greater increases in these outcomes with no discriminatory value within or between umbilical artery and umbilical vein pH and BE. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine umbilical cord oxygen saturation and fractional oxygen extraction values as measured at birth for a large tertiary hospital population and their predictive value for measures of acidosis.Study Design: The computerized perinatal database of St. Joseph's Health Centre, London, Ontario, was used to obtain the umbilical cord gases, pH, mode of delivery, gestational age at delivery, and nuchal cord status for all live-born infants >500 gm between January 1991 and December 1995 (n = 22,134). Oxygen saturation values were calculated from the umbilical cord PO2 and pH data with a previously derived empirical equation, the accuracy of which was rechecked with 100 consecutive cord blood samples where oxygen saturation values were both calculated and measured with a hemoximeter (r = 0.99, p = 0.001). Fractional oxygen extraction values were calculated from the umbilical cord oxygen saturation data.Results: There were 18,250 "validated" paired umbilical vein and artery blood gas and pH results available for analysis after patient case exclusions for missing, unreliable, or "unphysiologic" data. For all validated patient cases, mean umbilical vein oxygen saturation was 63% +/- 16% (SD), mean umbilical artery oxygen saturation was 24% +/- 15%, and mean fractional oxygen extraction was 0.62 +/- 0.20, with all three of these parameters significantly affected by mode of delivery, gestational age at delivery, and nuchal cord status. Umbilical vein and artery oxygen saturation and fractional oxygen extraction values showed significant relationships with umbilical artery base excess, albeit weak (r = 0.18 to 0.22), and pH (r = 0.46), which were best described using cubic regression models. Receiver-operator characteristic curve statistics for the prediction of acidosis at birth were also significant for all three of these parameters but lower when predicting metabolic versus mixed acidosis. However, all showed a poor positive predictive value for significant acidosis at birth, whether metabolic or mixed and regardless of the cutoff values used.Conclusion: Umbilical cord oxygen saturation and fractional oxygen extraction values as measured at birth for a large tertiary hospital population indicate a decreased oxygen margin of safety for infants born postterm, by cesarean section after labor, and with a nuchal cord. However, these values have a limited relationship to measures of acidosis, which may have clinical implications for the usefulness of intrapartum pulse oximetry. [ABSTRACT FROM AUTHOR]

Aclarubicin is an anthracycline antibiotic that differs from doxorubicin in its structure, mechanism of action, and preclinical toxicity profile, especially its reduced cardiotoxicity. We therefore conducted a side-by-side in vivo and in vitro trial of this agent in metastatic breast-cancer patients and their biopsied tumor specimens, respectively. Aclarubicin (100 mg/m2) was given by intravenous infusion every 3 weeks to 22 patients with objectively measurable metastatic breast cancer, 15 of whom had not previously received doxorubicin. The dose-limiting toxicity consisted primarily of leukopenia and severe nausea and vomiting. No objective response was observed in the 19 evaluable patients. After disease progression, 10 of the 15 doxorubicin-naive patients were treated with doxorubicin; 6 patients achieved a partial response, including 4 who responded to doxorubicin alone and 2 who responded to doxorubicin in combination with thiotepa and vinblastine. Tumor specimens were obtained from 14 of the 22 patients prior to the start of therapy and were tested for in vitro sensitivity to aclarubicin and doxorubicin using a soft agar colony-forming assay. Adequate colony growth occurred in 9 of 14 cultured tumor specimens. All 9 specimens, including 3 obtained from doxorubicin-naive patients, demonstrated in vitro resistance to aclarubicin. In all, 1 of 3 specimens taken from doxorubicin-naive patients demonstrated in vitro sensitivity to doxorubicin, whereas 6 tumor specimens obtained from patients who had undergone prior doxorubicin therapy demonstrated in vitro resistance. The patient whose tumor demonstrated in vitro doxorubicin sensitivity responded to a doxorubicin regimen after failing aclarubicin treatment; in vitro doxorubicin resistance correlated with clinical resistance in all cases. We conclude that aclarubicin is inactive in metastatic breast cancer at the dose and schedule used. Side-by-side in vivo and in vitro trials are feasible and could be useful in the development of investigational agents with activity greater than that of aclarubicin and, particularly, in the evaluation of analogs of clinically active drugs. [ABSTRACT FROM AUTHOR]