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The Breast Journal 11/2010; 16(6):663-5. · 1.64 Impact Factor
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Alison Stopeck
Clinical advances in hematology & oncology: H&O 03/2010; 8(3):159-60.
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ABSTRACT: As the efficacy of treatment for breast cancer has improved, particularly with the use of antiestrogenic therapies, there is an increasing population of long-term breast cancer survivors who seeks care with unique health issues. These patients may be at increased risk for cardiovascular disease (CVD) resulting from excess adiposity and treatment effects. Metabolic syndrome (MetS) and elevated C-reactive protein (CRP), two predictors of CVD, have not been fully evaluated in overweight breast cancer survivors on hormone-modulating agents.
Anthropometric measures, including weight, height, waist and hip circumferences; clinical laboratory assessments, including lipids, glucose, glycoslyated hemoglobin (HbA1c), insulin, and high sensitivity CRP; and body composition and blood pressure (BP) were collected from overweight breast cancer survivors (n=42). Select measures were used to derive MetS using the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) diagnostic criteria.
Participants had a mean body weight of 83.8 kg and body mass index (BMI) of 31.4 kg/m2. Mean fasting glucose (98+/-12.9 mg/dL), HbA1c (6.0+/-0.5 mg/dL), cholesterol (199+/-33.7 mg/dL), and insulin (16+/-3.2 mg/dL) were all at the upper end of the normal range. MetS was diagnosed in 54.8% of overweight postmenopausal breast cancer survivors. CRP was moderately or severely elevated in 90.5% of the population (mean of 5.1+/-5.3 mg/dL).
In our sample, overweight breast cancer survivors commonly have MetS and elevated CRP that place them at increased risk for cardiovascular and other metabolic diseases. If replicated in a larger sample, this warrants close medical monitoring to prevent and reduce morbidity and mortality unrelated to breast cancer.
Journal of Women s Health 12/2009; 18(12):2041-7. · 1.57 Impact Factor
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ABSTRACT: This is the first report of the Southwest oncology group phase II trial of single agent bevacizumab in patients with relapsed, aggressive non-Hodgkin lymphoma (NHL). Fifty-two patients in first or second relapse with diffuse large B-cell or mantle cell lymphoma were enrolled. Patients were treated with bevacizumab at 10 mg/kg every 2 weeks. Therapy was well tolerated with no unexpected toxicities observed. Six-month progression-free survival (PFS) was 16% with a response rate of 2% and median duration of response or stable disease of 5.2 months (range 3.5-72.7). Vascular endothelial growth factor A (VEGF) and VEGF receptor expression was observed in 70% and 65% of specimens, respectively. In an exploratory subgroup analysis, baseline urine VEGF and plasma vascular cell adhesion molecule-1 (VCAM) levels correlated with survival. Prolonged PFS in several patients as well as biomarker studies suggest the VEGF pathway plays an important role in aggressive NHL. Clinical trials combining active chemotherapy regimens with VEGF targeted agents are currently in progress.
Leukemia & lymphoma 05/2009; 50(5):728-35. · 2.40 Impact Factor
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ABSTRACT: Breast cancer is the most common nondermatological malignancy in women, and the incidence increases with age until the eighth decade. Breast cancer pathology and biology appear to be different in elderly patients than in younger ones, and therefore treatment recommendations cannot be generalized from one group to the other. Most elderly women can tolerate breast cancer surgery without significant complications and should be offered a definitive surgical procedure. Improved mechanisms to predict which patients will tolerate and benefit from various therapies are under development. Because most breast cancers in the elderly are hormone responsive, hormonal therapy remains the mainstay of systemic treatment in the adjuvant and metastatic settings. Chemotherapy can be used in elderly women, but treatment decisions must be individualized based upon risk-benefit analyses. Elder-specific studies are underway to identify the most-efficacious and best-tolerated therapies for breast cancer in this population. Primary care physicians must be aware of these issues to provide adequate counseling and care to these patients.
Journal of the American Geriatrics Society 11/2007; 55(10):1636-44. · 3.74 Impact Factor
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ABSTRACT: We reported previously that >or=5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated.
CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of >or=5 CTCs/7.5 mL at each blood draw.
Median PFS times for patients with <5 CTC from each of the five blood draw time points were 7.0, 6.1, 5.6, 7.0, and 6.0 months, respectively. For patients with >or=5 CTC, median PFS from these same time points was significantly shorter: 2.7, 1.3, 1.4, 3.0, and 3.6 months, respectively. Median OS for patients with <5 CTC from the five blood draw time points was all >18.5 months. For patients with >or=5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different.
Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.
Clinical Cancer Research 07/2006; 12(14 Pt 1):4218-24. · 7.74 Impact Factor
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Massimo Cristofanilli,
Daniel F Hayes,
G Thomas Budd,
Mathew J Ellis, Alison Stopeck,
James M Reuben,
Gerald V Doyle,
Jeri Matera,
W Jeffrey Allard,
M Craig Miller,
Herbert A Fritsche,
Gabriel N Hortobagyi,
Leon W M M Terstappen
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ABSTRACT: Metastatic breast cancer (MBC) is incurable; its treatment is palliative. We investigated whether the presence of circulating tumor cells (CTCs) predicts treatment efficacy, progression-free survival (PFS), and overall survival (OS) in patients with newly diagnosed MBC who were about to start first-line therapy.
One hundred seventy-seven patients with measurable MBC were enrolled onto a prospective study. Eighty-three of the 177 patients were entering first-line treatment, and these patients are the focus of this analysis. CTCs from 7.5 mL of whole blood drawn before treatment initiation (baseline) and monthly thereafter for up to 6 months were isolated and enumerated using immunomagnetics.
The mean (+/- standard deviation) follow-up time was 11.1 +/- 4.4 months (median, 12.2 months). Forty-three patients (52%) had > or = five CTCs at baseline. The median PFS was 7.2 months (95% CI, 4.9 to 9.4 months), and the median OS was more than 18 months. Patients with > or = five CTCs at baseline and at first follow-up (4 weeks) had a worse prognosis than patients with less than five CTCs (baseline: median PFS, 4.9 v 9.5 months, respectively; log-rank, P = .0014; median OS, 14.2 v > 18 months, respectively; log-rank, P = .0048; first follow-up: median PFS, 2.1 v 8.9 months, respectively; log-rank, P = .0070; median OS, 11.1 v > 18 months, respectively; log-rank, P = .0029). CTCs before and after the initiation of therapy were strong, independent prognostic factors.
Detection of CTCs before initiation of first-line therapy in patients with MBC is highly predictive of PFS and OS. This technology can aid in appropriate patient stratification and design of tailored treatments.
Journal of Clinical Oncology 03/2005; 23(7):1420-30. · 18.37 Impact Factor
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Massimo Cristofanilli,
G Thomas Budd,
Matthew J Ellis, Alison Stopeck,
Jeri Matera,
M Craig Miller,
James M Reuben,
Gerald V Doyle,
W Jeffrey Allard,
Leon W M M Terstappen,
Daniel F Hayes
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ABSTRACT: We tested the hypothesis that the level of circulating tumor cells can predict survival in metastatic breast cancer.
In a prospective, multicenter study, we tested 177 patients with measurable metastatic breast cancer for levels of circulating tumor cells both before the patients were to start a new line of treatment and at the first follow-up visit. The progression of the disease or the response to treatment was determined with the use of standard imaging studies at the participating centers.
Outcomes were assessed according to levels of circulating tumor cells at baseline, before the patients started a new treatment for metastatic disease. Patients in a training set with levels of circulating tumor cells equal to or higher than 5 per 7.5 ml of whole blood, as compared with the group with fewer than 5 circulating tumor cells per 7.5 ml, had a shorter median progression-free survival (2.7 months vs. 7.0 months, P<0.001) and shorter overall survival (10.1 months vs. >18 months, P<0.001). At the first follow-up visit after the initiation of therapy, this difference between the groups persisted (progression-free survival, 2.1 months vs. 7.0 months; P<0.001; overall survival, 8.2 months vs. >18 months; P<0.001), and the reduced proportion of patients (from 49 percent to 30 percent) in the group with an unfavorable prognosis suggested that there was a benefit from therapy. The multivariate Cox proportional-hazards regression showed that, of all the variables in the statistical model, the levels of circulating tumor cells at baseline and at the first follow-up visit were the most significant predictors of progression-free and overall survival.
The number of circulating tumor cells before treatment is an independent predictor of progression-free survival and overall survival in patients with metastatic breast cancer.
New England Journal of Medicine 08/2004; 351(8):781-91. · 53.30 Impact Factor
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Maurizio Zangari,
Elias Anaissie, Alison Stopeck,
Alyssa Morimoto,
Nguyen Tan,
Jeffrey Lancet,
Maureen Cooper,
Alison Hannah,
Guillermo Garcia-Manero,
Stephan Faderl,
Hagop Kantarjian,
Julie Cherrington,
Maher Albitar,
Francis J Giles
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ABSTRACT: Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with multiple myeloma (MM). VEGF, a soluble circulating angiogenic molecule, acts via receptor tyrosine kinases, including VEGF receptor 2. SU5416 is a small molecule VEGF receptor 2 inhibitor. Experimental Design: Adult patients with advanced MM were entered on a multicenter phase II study.
Twenty-seven patients (median age 69, range 39-79), median 4 (0-10) lines of prior therapy, 14 with prior thalidomide therapy, received SU5416 at 145 mg/m(2) twice weekly i.v. for a median of two 4-week cycles (range 0.2-9). Grade 3/4 toxicities were rarely observed; the most frequent was thrombocytopenia (12%). Mild-to-moderate toxicities included nausea (63%), headache (56%), diarrhea, vomiting (both 37%), and fatigue (33%). There were three thromboembolic episodes and five cases of new onset hypertension. Two (7%) patients did not complete the first 4-week cycle of therapy because of adverse events (pneumonia and headache). There were no objective responses. Four patients had disease stabilization for >/==" BORDER="0">4 months. A decrease in median VEGF plasma levels was observed in patients with stable disease (n = 7) compared with patients with progressive disease (n = 5). Overall median survival was 42 weeks (range 3-92+).
Although SU5416 had minimal clinical activity, signs of biological activity (decrease in plasma VEGF levels) suggest that angiogenic modulation may be of value in patients with MM.
Clinical Cancer Research 01/2004; 10(1 Pt 1):88-95. · 7.74 Impact Factor
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ABSTRACT: SU5416 is a small molecule antiangiogenic agent that inhibits vascular endothelial growth factor (VEGF) stimulation of the KDR tyrosine kinase receptor. In this Phase I dose escalation trial, a weekly dose schedule of SU5416 was tested whereby an initial 5-day loading dose was followed by weekly maintenance infusions. The start dose was 20 mg/m(2) for the loading dose followed by 65 mg/m(2) for the weekly infusions. Dose escalations occurred at 33% until a final dose of 65 mg/m(2) (loading dose) and 190 mg/m(2) (weekly infusion) was obtained. Twenty-two patients were treated at five dose levels; tumor types included gastrointestinal (8), breast (3), lung (4), sarcoma (2), and other (5). The most common serious drug-related toxicity was headache, often associated with nausea and vomiting. Grade 1 and 2 toxicities included headache, nausea, vomiting, asthenia, pain at the infusion site, phlebitis, change in voice, and fevers. Of 19 evaluable patients, 4 obtained clinical benefit as defined by tumor regression (1) or disease stabilization for at least 12 weeks (3). Pharmacokinetic data revealed that the weekly infusion schedule prevented the reported 50-60% induction in SU5416 clearance observed with either daily or twice weekly dosing. Higher baseline levels of urine VEGF were observed in the 4 patients who gained clinical benefit, suggesting this may be a useful marker for predicting response to anti-VEGF therapies. Our results suggest that a weekly schedule of SU5416 shows signs of biological activity and is well tolerated at doses up to 145 mg/m(2).
Clinical Cancer Research 10/2002; 8(9):2798-805. · 7.74 Impact Factor
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ABSTRACT: The goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60 measurable liver lesions were monitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy.
Neoplasia 6(6):831-7. · 5.95 Impact Factor
