9 research outputs found
Inflammatory breast cancer: dynamic contrast-enhanced MR in patients receiving bevacizumab. Initial experience
To retrospectively compare three dynamic contrast material-enhanced
magnetic resonance (MR) imaging (dynamic MR imaging) analytic methods to
determine the parameter or combination of parameters most strongly associated
with changes in tumor microvasculature during treatment with bevacizumab alone
and bevacizumab plus chemotherapy in patients with inflammatory or locally
advanced breast cancer. MATERIALS AND METHODS: This study was conducted in
accordance with the institutional review board of the National Cancer Institute
and was compliant with the Privacy Act of 1974. Informed consent was obtained
from all patients. Patients with inflammatory or locally advanced breast cancer
were treated with one cycle of bevacizumab alone (cycle 1) followed by six cycles
of combination bevacizumab and chemotherapy (cycles 2-7). Serial dynamic MR
images were obtained, and the kinetic parameters measured by using three dynamic
analytic MR methods (heuristic, Brix, and general kinetic models) and two
region-of-interest strategies were compared by using two-sided statistical tests.
A P value of .01 was required for significance. RESULTS: In 19 patients, with use
of a whole-tumor region of interest, the authors observed a significant decrease
in the median values of three parameters measured from baseline to cycle 1:
forward transfer rate constant (Ktrans) (-34% relative change, P=.003), backflow
compartmental rate constant extravascular and extracellular to plasma (Kep) (-15%
relative change, P<.001), and integrated area under the gadolinium concentration
curve (IAUGC) at 180 seconds (-23% relative change, P=.009). A trend toward
differences in the heuristic slope of the washout curve between responders and
nonresponders to therapy was observed after cycle 1 (bevacizumab alone, P=.02).
The median relative change in slope of the wash-in curve from baseline to cycle 4
was significantly different between responders and nonresponders (P=.009).
CONCLUSION: The dynamic contrast-enhanced MR parameters Ktrans, Kep, and IAUGC at
180 seconds appear to have the strongest association with early physiologic
response to bevacizumab. Clinical trial registration no. NCT0001654
Measuring ovarian toxicity in clinical trials: Measuring ovarian toxicity in clinical trials: an American Society of Clinical Oncology research statement
A U.S. Food and Drug Administration (FDA) pooled analysis of outcomes for bone only metastatic breast cancer (MBC).
Modernizing clinical trial eligibility criteria: Recommendations of the ASCO-Friends of Cancer Research Prior Therapies Work Group
PURPOSE: Restrictive eligibility criteria induce differences between clinical trial and real-world treatment populations. Restrictions based on prior therapies are common; minimizing them when appropriate may increase patient participation in clinical trials.
EXPERIMENTAL DESIGN: A multi-stakeholder working group developed a conceptual framework to guide evaluation of prevailing practices with respect to using prior treatment as selection criteria for clinical trials. The working group made recommendations to minimize restrictions based on prior therapies within the boundaries of scientific validity, patient centeredness, distributive justice, and beneficence.
RECOMMENDATIONS: (i) Patients are eligible for clinical trials regardless of the number or type of prior therapies and without requiring a specific therapy prior to enrollment unless a scientific or clinically based rationale is provided as justification. (ii) Prior therapy (either limits on number and type of prior therapies or requirements for specific therapies before enrollment) could be used to determine eligibility in the following cases: a) the agents being studied target a specific mechanism or pathway that could potentially interact with a prior therapy; b) the study design requires that all patients begin protocol-specified treatment at the same point in the disease trajectory; and c) in randomized clinical studies, if the therapy in the control arm is not appropriate for the patient due to previous therapies received. (iii) Trial designers should consider conducting evaluation separately from the primary endpoint analysis for participants who have received prior therapies.
CONCLUSIONS: Clinical trial sponsors and regulators should thoughtfully reexamine the use of prior therapy exposure as selection criteria to maximize clinical trial participation