Abbott Endo-A results in prostate cancer metastasized to the bone.
[I would like to understand the relationship among Endothelin-A antagonists and the separate indications pursued by Abbott (cancer) and TXB/ICOS (cardio/vascular). The two drugs might not even be at all similar, still it should be useful that Abbott, running the cancer trials, will not be shy in reporting toxicity.]
--Wilder
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Sunday May 13, 12:30 pm Eastern Time
Press Release
SOURCE: Abbott Laboratories
Data Suggests Abbott Laboratories' Atrasentan (ABT-627) Inhibits Progression Of Bone Metastases in End-Stage Prostate Cancer
-- First Endothelin-A Receptor Antagonist Under Evaluation in Oncology --
SAN FRANCISCO, May 13 /PRNewswire/ -- Phase II data presented at the annual meeting of the American Society of Clinical Oncology (ASCO) suggest that atrasentan (ABT-627), Abbott Laboratories' investigational endothelin-A receptor antagonist, can inhibit the progression of bone metastases (spread of cancer to the bone) in patients with end-stage, or hormone-refractory, prostate cancer.
Data pooled from two studies showed that patients taking a 10 mg oral dose of atrasentan once daily maintained levels of key biochemical markers, including serum total and bone alkaline phosphatase, consistent with the levels measured at the start of the study. Elevations of these markers indicate progressive metastatic disease in bone and are associated with poor prognosis. This result was significantly different from the result in patients taking placebo, who experienced increases in levels of these biochemical markers (p<0.001).
``These data suggest that atrasentan may impact the progression of hormone-refractory prostate cancer by delaying the development of skeletal metastases,'' said Joel Nelson, M.D., professor and chairman of urology, University of Pittsburgh Medical Center and lead investigator in the study. ``Skeletal metastases are indicative of late-stage prostate cancer. This study is promising for late-stage prostate cancer.''
These data were pooled from two multinational, double-blind studies totaling 419 men with hormone-refractory prostate cancer who were randomized to receive either a 2.5 mg or 10 mg oral dose of atrasentan once daily, or placebo.
Bone markers of metastatic disease progression, including levels of serum total and bone alkaline phosphatase, collagen crosslinked N-telopeptides, and deoxypyridinoline were measured at the start of the study and were compared to the measurements taken through the course of the study. In the patients receiving atrasentan, a dose-dependent response was observed; in patients receiving the 10 mg dose of atrasentan, the total and bone alkaline phosphotase concentrations remained consistent with baseline levels. This result was statistically significant compared to the results in patients taking placebo where increases in all markers ranged from 20 to 97 percent (p<0.005). Patients receiving the 2.5 mg dose of atrasentan experienced increases in biochemical markers that were lower than the increase seen in patients taking placebo.
The most common adverse events, with the 10 mg dose of atrasentan vs. placebo, were peripheral edema (39 percent vs. 19 percent), rhinitis (28 percent vs. 12 percent), headache (23 percent vs. 12 percent) and constipation (22 percent vs. 12 percent). These adverse events were mild to moderate in severity and were associated with few discontinuations. Only one patient receiving atrasentan discontinued use based on one of these three adverse events.
``We are excited to be presenting results from these Phase II studies that suggest that atrasentan may impact hormone-refractory prostate cancer,'' said Azmi Nabulsi, M.D., head of clinical development for atrasentan at Abbott. ``Elevated levels of biochemical markers indicate the spread of cancer to the bone. This study indicates that blocking the effects of the endothelin-1 protein may play a role in delaying the progression of prostate cancer.''
Atrasentan is currently beginning Phase III clinical trials in patients with hormone-refractory prostate cancer.
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Abbott Laboratories' Atrasentan (ABT-627) Helped Patients Maintain Health State Consistent with Baseline As Measured by Quality of Life
-- Patients Experienced Delay in Progression of Prostate Cancer --
SAN FRANCISCO, MAY 13 /PRNewswire/ -- Phase II data presented at the annual meeting of the American Society of Clinical Oncology (ASCO) showed that atrasentan (ABT-627), Abbott Laboratories' investigational endothelin-A receptor antagonist, delayed the progression of disease in patients with end-stage, or hormone-refractory, prostate cancer, allowing patients to remain in a favorable state of health similar to baseline (as measured at start of study) for a longer duration of time, compared to placebo.
Patients with end-stage prostate cancer often experience disease progression that leads to bone metastases (spread of cancer to the bone), which can be painful. Results from this study showed that patients treated with an oral 10 mg dose of atrasentan once-daily experienced nearly a 30 percent improvement in quality-adjusted time to progression (QATTP). This measures the length of time from initiation of therapy to clinical progression of the disease, taking into account changes in the patient's self-perception of health status and general well-being.
``Conventional analysis in treatment trials often does not assess the impact of the treatment on a patient's daily life and perception of well-being,'' said Perry Nisen, M.D., divisional vice president, Oncology Drug Development at Abbott. ``We believe this study is important because it demonstrates that atrasentan may be able to delay progression of the disease and also help patients maintain the self-perception of general well-being for a longer period of time.''
``The results of this study are encouraging,'' said Azmi Nabulsi, M.D., head of Clinical Development for atrasentan at Abbott. ``Currently, there is an unmet medical need for treatments for late-stage prostate cancer, which is associated with a decline in patients' quality of life.''
In this Phase II multinational, double-blind study, 288 patients were randomized to receive either an oral dose of 2.5 mg or 10 mg of atrasentan once-daily, or placebo. Study participants' quality of life was measured using the EORTC QLQ C-30 and FACT-P instruments, which track patients' self-perception of health based upon their symptoms, ability to function and sense of well-being.
A Kaplan-Meier analysis, commonly used in oncology trials, showed the QATTP for patients treated with 10 mg of atrasentan was significantly longer than the placebo group for most domains of the EORTC and FACT instruments (p<0.05). Additionally, the data showed strong trends in favor of the 10 mg dose in other domains (p<0.10). Overall, the patients treated with the 10 mg or 2.5 mg dose of atrasentan experienced an average 28 or 38 percent increase, respectively, in the median QATTP over placebo. Improvement in QATTP also correlated with a statistically significant delay in clinical and prostate-specific antigen (PSA) progression for patients taking atrasentan.
The most common adverse events, with the 10 mg dose of atrasentan vs. placebo were peripheral edema (35 percent vs. 14 percent), rhinitis (29 percent vs. 13 percent), and headache (20 percent vs. 10 percent). These adverse events were mild to moderate in severity and were associated with few discontinuations.
Atrasentan is currently beginning Phase III clinical trials in patients with hormone-refractory prostate cancer. |
