Docetaxel (T) given concurrently with or sequentially to anthracycline-based (A) adjuvant therapy (adjRx) for patients (pts) with node-positive (N+) breast cancer (BrCa), in comparison with non-T adjRx: First results of the BIG 2–98 Trial at 5 years median follow-up (MFU)

LBA519 Background: The activity of T in metastatic BrCa mandated evaluation as adjRx. We compared the efficacy of T with, or after A, both followed by CMF (cyclophosphamide/ methotrexate/ 5-fluorouracil), versus non-T adjRx. Methods: Random assignment trial in resected N+ pts, 18–70 yrs, stratified by: center, 1–3 vs >3 nodes and age <50 vs ≥50. The treatment arms were (mg/m2, intravenously unless otherwise stated): Ia: A 75 q 3 weeks × 4 ⋄ CMF ×3 (oral C 100 day 1–14, F 600 + M 40 d 1+8; q 28 days). Arm Ib; AC 60/600 × 4⋄CMF × 3. Arm II: A75 × 3 ⋄T100 ×3 ⋄CMF ×3. Arm III: AT 50/75 ×4 ⋄ CMF × 3. Pts subsequently received hormono-(receptor+), and radiotherapy per local guidelines. Randomization was in the ratio (1:1:2:2). The trial was designed to have 80% power to detect a 78% hazard ratio (HR) for relapse in II+III v I, with final analysis at 1215, and interim at 405 and 810 events. The primary comparison between the II+III and I would be done at a one-tailed significance level of 0.025. Secondary comparisons of II vs Ia and III vs Ib would be done using a closed testing procedure at a one-tailed significance level of 0.025. The 95% confidence limits of the HR of III v II would be calculated. Due to a low relapse rate, the plan was amended with main analysis after 810 events or 5 years MFU. Results: 2887 pts were enrolled (6/1998–6/2001). Characteristics were well-balanced, 46% had >3N+. Grade 3/4 toxicity occurred in 22.9, 24.7, 35.3 and 28.6 % of pts in Ia, Ib, II and III respectively. At 62.2 months MFU (3/2006), 732 pts (25%) had events. Planned event-free survival (EFS) comparisons were: Conclusion: In this study, the HR for T v non-T adjRx was of borderline significance. There were possibly important differences related to schedule, sequential but not concurrent appearing superior to non-T adjRx. Overall survival analysis will require longer follow-up. Translational studies are underway. [Table: see text] [Table: see text]

Review of Actual Proficiency-Testing Performance Under CLIA '67 (March 14, 1990) Rules: Perspective from the First Year's Data

Under the Clinical Laboratory Improvement Act of 1967 the Health Care Financing Administration's proficiency-testing requirement applies to approximately 12,000 hospital, reference, and large-clinic laboratories in the United States. The Wisconsin State Laboratory of Hygiene is approved by the Health Care Financing Administration to provide proficiency testing in all specialties and subspecialties. The focus of the program is to provide highly specialized service and support to a limited number of participants in order to assess intralaboratory performance correctly. We report the findings over the four proficiency-testing events in 1991 for the subspecialty of routine chemistry, which serves approximately 470 participants. Failure rates for individual analytes on single proficiency testing events ranged from 0% to 13%. After four events or one year, if the mandated evaluation criteria and failure rules were strictly applied, as many as 11% of the laboratories could have found themselves involuntarily suspended from offering all routine chemistry testing.