- Subject: Pharmacyclics Announces Interim Gd-Tex Results at...
- From: AOL News <AOLNews@aol.com>
- Date: Tue, 19 May 1998 11:07:51 EDT
- Organization: AOL (http://www.aol.com)
Pharmacyclics Announces Interim Gd-Tex Results at American Society of Clinical
Oncology Meeting
Survival Analyses Indicate Treatment with Gd-Tex Leads to Improved Outcome
SUNNYVALE, Calif., May 19 /PRNewswire/ -- Pharmacyclics, Inc. (Nasdaq: PCYC)
today announced certain interim results of a phase Ib/II clinical trial of its
radiation sensitizer gadolinium texaphyrin (Gd-Tex) for the treatment of brain
metastases. Results are being presented at the annual meeting of the American
Society of Clinical Oncology (ASCO) in Los Angeles.
Sixty-one patients were enrolled in the combined phase Ib/II multi-center
trial designed to give 10 daily intravenous injections of Gd-Tex, each
followed by whole brain radiation for treatment of brain metastases. Thirty-
nine patients were enrolled in the phase Ib portion of the study designed to
determine the dose-limiting toxicity and tumor localization using magnetic
resonance imaging (MRI). Based on phase Ib results, an additional 22 patients
were entered in the phase II portion designed to evaluate toxicity,
pharmacokinetics and tumor response in patients receiving optimized dosing of
Gd-Tex. Interim tumor response data were available and reported for 37
patients in the combined phase Ib/II trial. The overall tumor response rate
(defined as complete plus partial response rate) for the combined study was
73%. In the phase II portion of the trial, interim tumor response data were
available and reported for 17 patients. Of 17 patients completing adequate
follow-up in phase II, 13 responses were observed for a response rate of 76%.
Five of the 22 patients entered in the phase II portion of the study were not
evaluable for tumor response due to early death (2 patients), or are still on
study and have not yet received follow-up scans (3 patients). Tumor responses
were evaluated by an independent review of serial MRI scans of the head.
Enrollment in the phase Ib/II clinical trial was completed in March 1998. Of
the 61 patients enrolled in phase Ib/II, 35 had lung cancer, 10 had breast
cancer, 6 had melanoma and 10 had other primary tumor types.
Gd-Tex was administered as a rapid intravenous infusion without significant
infusional toxicity. In phase Ib, the dose-limiting toxicity was reversible
elevation of liver enzymes. In the combined phase Ib/II trial, grade 3 or
grade 4 toxicity was seen in 7 out of 61 patients (11%). Many of the observed
adverse reactions are known to occur frequently in patients with brain
metastases and thus were considered drug or possibly drug-related.
MRI scanning was used to confirm that Gd-Tex accumulated selectively in the
tumors and not in adjacent normal brain, confirming previous results from
phase I studies showing that the drug localizes in tumors.
An intent-to-treat survival analysis was performed on 60 patients (the final
patient treated was excluded due to short follow-up) enrolled in the phase
Ib/II study and compared to a historical database. This database contains
information on treatment, survival and prognostic features in 499 patients
with brain metastases treated with radiation therapy. Three statistical
methods were used to compare outcome in the Gd-Tex treated patients to the
historical control patients. A case-matched control analysis of survival, a
log-rank comparison of survival, and a proportional hazards comparison to
identify prognostic factors of survival were used to compare Gd-Tex treated
patients with the historical control group.
In each analysis, patients receiving Gd-Tex had a statistically significant
improved outcome compared to the historical control. For each Gd-Tex treated
patient, three matched control patients were selected from the data set based
on the six most important prognostic factors. The survival of each Gd-Tex
treated patient versus its matched group was assessed. The odds of surviving
two months, four months or six months were 2.5, 1.7 and 2.0 times,
respectively as great for the Gd-Tex treated patients as for the matched
historical control groups. Using a log-rank analysis, patients receiving Gd-
Tex had a 40% longer median survival compared to control patients (4.9 months
versus 3.5 months, p=0.012). When Gd-Tex treated and control patients were
combined, a proportional hazard comparison identified Gd-Tex as one of the
most important independent prognostic factors in determining survival. The
risk of death was 61% higher in control patients than in the patients
receiving Gd-Tex.
"The data suggests that patients receiving Gd-Tex and radiation therapy for
treatment of brain metastases have improved tumor response rate and survival,"
said medical oncologist Markus Renschler, M.D., senior director of clinical
research at Pharmacyclics and a co-author on the study. "Although this was
not a prospective study, a rigorous and comprehensive statistical evaluation
was performed, based on multiple analyses, including case matching to improve
comparability of Gd-Tex treated patients with historical control patients."
Richard A. Miller, M.D., president and chief executive officer of the company,
stated that, "We are very pleased by the results of the phase Ib/II study and
are looking forward to the initiation of a prospective randomized phase III
study in mid-1998."
The study was conducted at 12 medical centers including: Comprehensive Cancer
Center of Wake Forest University, Bowman Gray School of Medicine; Cooper
Hospital Medical Center, UMDNJ Robert Wood Johnson Medical School; Indiana
University Medical Center; Institut Gustave Roussy, Villejuif, France; Joint
Center for Radiation Therapy, Harvard Medical School; Northwest Kinetics, LLC;
Thompson Cancer Survival Center; UCLA Medical Center; University of Texas, MD
Anderson Cancer Center; University of Virginia Health Sciences Center;
University of Washington; and University of Wisconsin.
Gd-Tex, one of a group of patented synthetic molecules called texaphyrins,
captures and focuses medically useful forms of energy, such as X-rays, which
are used in the radiation therapy of cancer. In preclinical and clinical
trials, Gd-Tex was shown to selectively accumulate in cancer cells, and, when
activated by X-ray energy (radiation therapy), Gd-Tex appears to increase the
damage to cancer cells without increasing the damage to normal cells.
Metastases to the brain are one of the most devastating consequences of
cancer, affecting up to 20% of all cancer patients. Brain metastases occur
when cancer cells become dislodged from their primary site and travel to the
brain where they take up residence and grow. The consequences of brain
metastases are devastating and include headaches, seizures, paralysis,
blindness and death. In the United States, about 170,000 patients receive
radiation therapy each year for the treatment of brain metastases. By
harnessing X-ray energy, Gd-Tex is designed to enhance the efficacy of cancer
radiation therapy.
Radiation therapy is used to treat 700,000 cancer patients per year in the
United States. Like many cancer treatments, radiation is indiscriminate, and
is cytotoxic to the tumors and surrounding tissues. A major limitation of
radiation therapy is related to the damage it causes to surrounding organs.
Pharmacyclics is a pharmaceutical company developing energy-potentiating drugs
to improve radiation therapy and chemotherapy of cancer, and to enable or
improve the photodynamic therapy of certain cancers and atherosclerotic
cardiovascular disease. The company's products are small ring-shaped
molecules, called "texaphyrins," which are patented agents derived from
Pharmacyclics' versatile technology platform for designing and synthesizing
energy-potentiating drugs. These texaphyrins localize in cancer cells and
atherosclerotic plaque, where they can be activated by forms of energy,
including X-ray, chemical and light, to eliminate diseased tissue.
The statements made in this press release may contain certain forward-looking
statements that involve a number of risks and uncertainties. Actual events or
results may differ from the company's expectations. In addition to the
matters described in this release, future actions by the U.S. Food and Drug
Administration and other domestic and foreign regulatory agencies, the
initiation, timing and results of pending or future clinical trials, as well
as risk factors listed from time to time in the company's reports as filed
with the U.S. Securities and Exchange Commission, including but not limited
to, its reports on Forms 10-Q and 10-K, may affect the actual results achieved
by the company.
SOURCE Pharmacyclics, Inc.
CO: Pharmacyclics, Inc.
ST: California
IN: MTC
SU: PDT
05/19/98 11:01 EDT http://www.prnewswire.com
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