High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles ( 3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses ( median cumulative dose 339 mg/m(2)) was administered ( range: 2 - 18). The overall response rate was 48.1% ( 95% CI: 34 - 61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months ( intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status. Copyright (C) 2005 S. Karger AG, Basel

Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment

Symptoms are common among patients receiving treatment for advanced cancers, yet are undetected by clinicians up to half the time. There is growing interest in integrating electronic patient-reported outcomes (PROs) into routine oncology practice for symptom monitoring, but evidence demonstrating clinical benefit has been limited

Return to work in low-income Latina and non-Latina white breast cancer survivors: A 3-year longitudinal study

BACKGROUND: Previous research has found an 80% return-to-work rate in mid-income white breast cancer survivors, but little is known about the employment trajectory of low-income minorities or whites. We set out to compare the trajectories of low-income Latina and non-Latina white survivors and to identify correlates of employment status. METHODS: Participants were low-income women who had localized breast cancer, spoke English or Spanish, and were employed at the time of diagnosis. Interviews were conducted 6, 18, and 36 months after diagnosis. Multivariate logistic regression was used to identify independent correlates of employment status at 18 months. RESULTS: Of 290 participants, 62% were Latina. Latinas were less likely than non-Latina whites to be working 6 months (27% vs 49%; P =.0002) and 18 months (45% vs 59%; P =.02) after diagnosis, but at 36 months there was no significant difference (53% vs 59%; P =.29). Latinas were more likely to be manual laborers than were non-Latina whites (P <.0001). Baseline job type and receipt of axillary node dissection were associated with employment status among Latinas but not non-Latina whites. CONCLUSIONS: Neither low-income Latinas nor non-Latina whites approached the 80% rate of return to work seen in wealthier white populations. Latinas followed a protracted return-to-work trajectory compared to non-Latina whites, and differences in job type appear to have played an important role. Manual laborers may be disproportionately impacted by surgical procedures that limit physical activity. This can inform the development of rehabilitative interventions and may have important implications for the surgical and postsurgical management of patients

Plasmas and Controlled Nuclear Fusion

Contains reports on ten research projects split into three sections.National Science Foundation (Grant GK-2581

Applied Plasma Research

Contains research objectives and reports on three research projects.National Science Foundation (Grant GK-2581)Joint Services Electronics Program under Contract DA 28-043-AMC-02536(E

Quantum interference in asymmetric superconducting nanowire loops

Macroscopic phase coherence in superconductors enables quantum interference and phase manipulation at realistic device length scales. Numerous superconducting electronic devices are based on the modulation of the supercurrent in superconducting loops. While the overall behavior of symmetric superconducting loops have been studied, the effects of asymmetries in such devices remain under-explored and poorly understood. Here we report on an experimental and theoretical study of the flux modulation of the persistent current in a doubly-connected asymmetric aluminum nanowire loop. A model considering the length and electronic cross-section asymmetries in the loop provides a quantitative account of the observations. Comparison with experiments give essential parameters such as persistent and critical currents as well as the amount of asymmetry which can provide feedback into the design of superconducting quantum devices.Comment: to appear in EP

Survival, pathologic response, and genomics in CALGB 40601 (Alliance), a neoadjuvant Phase III trial of paclitaxel-trastuzumab with or without lapatinib in HER2-positive breast cancer

PURPOSE CALGB 40601 assessed whether dual versus single human epidermal growth factor receptor 2 (HER2) -targeting drugs added to neoadjuvant chemotherapy increased pathologic complete response (pCR). Here, we report relapse-free survival (RFS), overall survival (OS), and gene expression signatures that predict pCR and survival. PATIENTS AND METHODS Three hundred five women with untreated stage II and III HER2-positive breast cancer were randomly assigned to receive weekly paclitaxel combined with trastuzumab plus lapatinib (THL), trastuzumab (TH), or lapatinib (TL). The primary end point was pCR, and secondary end points included RFS, OS, and gene expression analyses. mRNA sequencing was performed on 264 pretreatment samples. RESULTS One hundred eighteen patients were randomly allocated to THL, 120 to TH, and 67 to TL. At more than 7 years of follow-up, THL had significantly better RFS and OS than did TH (RFS hazard ratio, 0.32; 95% CI, 0.14 to 0.71; P 5.005; OS hazard ratio, 0.34; 95% CI, 0.12 to 0.94; P 5.037), with no difference between TH and TL. Of 688 previously described gene expression signatures, significant associations were found in 215 with pCR, 45 with RFS, and only 22 with both pCR and RFS (3.2%). Specifically, eight immune signatures were significantly correlated with a higher pCR rate and better RFS. Among patients with residual disease, the immunoglobulin G signature was an independent, good prognostic factor, whereas the HER2-enriched signature, which was associated with a higher pCR rate, showed a significantly shorter RFS. CONCLUSION In CALGB 40601, dual HER2-targeting resulted in significant RFS and OS benefits. Integration of intrinsic subtype and immune signatures allowed for the prediction of pCR and RFS, both overall and within the residual disease group. These approaches may provide means for rational escalation and de-escalation treatment strategies in HER2-positive breast cancer

Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)

PURPOSE: To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC). PATIENTS AND METHODS: Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned. RESULTS: From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%). CONCLUSION: The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting

Persistence, adherence, and toxicity with oral CMF in older women with early-stage breast cancer (Adherence Companion Study 60104 for CALGB 49907)

Cyclophosphamide-methotrexate-5-fluorouracil (CMF) is often selected as adjuvant chemotherapy for older patients with early-stage breast cancer due to perceived superior tolerability. We sought to measure persistence with CMF, adherence to oral cyclophosphamide, and the association of these with toxic effects