- Phase II Trial Shows Increase in Mature Dendritic Cells - WAYNE, N.J., June 30
WAYNE, N.J., June 30 /PRNewswire-FirstCall/ -- Bayer HealthCare
Pharmaceuticals today confirmed that results of a Phase II trial were
published in the July 1 edition of the Journal of Clinical Oncology. The
study showed that Leukine(R) (sargramostim) demonstrated a median overall
survival of 65 months and increased mature dendritic cells in high-risk
melanoma patients. Dendritic cells are special antigen-presenting cells that
help the immune system recognize cancer cells and are the most effective
antigen-presenting cells known. Study authors concluded that this increase in
dendritic cell counts may also correlate with delayed recurrence of disease.
"These data provide early signals that Leukine may offer clinical benefit
in this patient group by increasing and differentiating dendritic cells and
perhaps by benefiting patients who have lowered baseline levels of dendritic
cells," said Dr. Adil Daud, first author of the study and Associate Professor,
Director, Clinical Research, University of California, San Francisco Melanoma
Center. "Patients who experienced an increase of dendritic cells were more
likely to demonstrate delayed disease recurrence."
In this Phase II prospective trial, 42 patients with resected high-risk
(Stage IIIB, IIIC or IV) melanoma were treated with Leukine (125 mcg/m2/day
for 14 consecutive days followed by 14 days of no treatment). This regimen
was repeated for 13 cycles unless patients had unacceptable toxicity or showed
evidence of disease recurrence. Patients had no evidence of disease at the
start of the trial as measured by imaging. Patients underwent restaging every
four months. The most common adverse events found in the study were injection
site reactions (88 percent), pain (61 percent), arthralgia/myalgia (61
percent), fatigue (61 percent), flu-like symptoms (39 percent) and insomnia
(27 percent).
Of the 42 enrolled patients, 39 were available for clinical outcome and
dendritic cell analysis. Results showed that the median overall survival was
65 months (95 percent, CI 43-67 months). Median recurrence-free survival was
5.6 months (95 percent, CI 3.7-11 months). Additionally, 11 patients who
relapsed within three months of starting Leukine had lower dendritic cell
counts at two weeks compared to those who relapsed after three months and
those who remained in remission throughout the course of the study. However,
the ability of Leukine to induce mature dendritic cells appeared to be
confined to those patients who had low dendritic cell count before the start
of treatment.
"We are encouraged about the potential of Leukine in high-risk melanoma in
this trial," said Paul MacCarthy, M.D., F.R.C.P.I., vice president and head of
U.S. Medical Affairs for Bayer HealthCare Pharmaceuticals. "We look forward
to additional research supporting Leukine's promise in this area as part of
our ongoing commitment to provide patients with effective and safe medicines."
About The Study
In addition to clinical outcomes, patients underwent phenotype analysis of
dendritic cells. Dendritic cell phenotypic analysis was performed at baseline
and again at two, four, eight and 12 weeks. Control values for this analysis
were established prior to the trial using eight healthy volunteers. Two weeks
of treatment with Leukine resulted in a significant increase in the proportion
of total mature dendritic cells as defined by expression of CD86, CD83, CCR7
and CD40 molecules. Further, results show that Leukine increased dendritic
cell populations in patients who started the study with lower than normal
levels of dendritic cells, but had no effect on patients who started the trial
with normal levels.
About Leukine(R)
Leukine(R) (sargramostim) is a growth factor that helps fight infection
and disease in appropriate patients by enhancing immune cell function.
Leukine was approved in the United States in 1991, and is marketed by Bayer
HealthCare Pharmaceuticals. Leukine is the only growth factor approved in the
U.S. for use following induction chemotherapy in older adults with acute
myelogenous leukemia (AML) to shorten the time to neutrophil recovery and
reduce the incidence of severe and life-threatening infections and infections
resulting in death. Leukine also has been approved in the U.S. for use in
four additional indications: myeloid reconstitution following allogeneic and
autologous bone marrow transplantation (BMT), peripheral blood stem cell
(PBSC) mobilization and subsequent myeloid reconstitution in patients
undergoing PBSC transplantation, and bone marrow transplantation failure or
engraftment delay. Leukine is available in two formulations, both of which are
suitable for IV infusion and subcutaneous injection:
-- Liquid: 500 mcg/mL sterile solution in multi-use vial
-- Lyophilized powder: 250 mcg in single-use vial ready for sterile
reconstitution
Leukine has been used to treat nearly 250,000 cancer patients in the U.S.
since 1991. Among its indications, Leukine is the only myeloid growth factor
approved to reduce the incidence of infections resulting in early death
following induction chemotherapy in older adults with AML.
Important Safety Considerations
Leukine is contraindicated in patients with excessive leukemic blasts in
bone marrow or peripheral blood (10 percent), in patients with known
hypersensitivity to GM-CSF, yeast derived products or any component of
Leukine, and for concomitant use with chemotherapy and radiotherapy. Serious
allergic or anaphylactic reactions have been reported with Leukine. If any
serious or anaphylactic reactions occur, Leukine therapy should immediately be
discontinued and appropriate therapy initiated. Leukine should be used with
caution and monitored in patients with preexisting fluid retention, pulmonary
infiltrates or CHF; respiratory symptoms or disease; cardiac symptoms or
disease; and renal or hepatic dysfunction. Edema, capillary leak syndrome,
pleural and or/pericardial effusion, supraventricular tachycardia,
sequestration of granulocytes in the pulmonary circulation and dyspnea have
been reported in patients after Leukine administration. Leukine has induced
the elevation of serum creatinine or bilirubin and hepatic enzymes in some
patients. Monitoring of renal and hepatic function in patients with
preexisting renal or hepatic dysfunction is recommended at least every other
week during Leukine administration. Adverse events occurring in 10 percent of
AML patients receiving Leukine in controlled clinical trials and reported in a
higher frequency than placebo were: fever, skin reactions, metabolic
disturbances, nausea, vomiting, weight-loss, edema, and anorexia. If ANC
20,000 cells/mm(3) or if platelet counts 500,000 mm(3), Leukine administration
should be interrupted or the dose reduced by half. Twice weekly monitoring of
CBC with differential should be performed. Leukine therapy should be
discontinued if disease progression is detected during treatment.
About Bayer HealthCare Pharmaceuticals Inc.
Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals
business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare
is one of the world's leading innovative companies in the healthcare and
medical products industry, and combines the activities of the Animal Health,
Consumer Care, Diabetes Care, and Pharmaceuticals divisions. Bayer HealthCare
Pharmaceuticals comprises the following business units: Women's Healthcare,
Diagnostic Imaging, General Medicine, which includes Cardiology and Primary
Care and Specialty Medicine, which includes Hematology, Oncology and Multiple
Sclerosis. The company's aim is to discover and manufacture products that
will improve human health worldwide by diagnosing, preventing and treating
diseases.
Forward-looking statements
This news release contains forward-looking statements based on current
assumptions and forecasts made by Bayer Group management. Various known and
unknown risks, uncertainties and other factors could lead to material
differences between the actual future results, financial situation,
development or performance of the company and the estimates given here. These
factors include those discussed in our annual and interim reports to the
Frankfurt Stock Exchange and in our reports filed with the U.S. Securities and
Exchange Commission (including our Form 20-F). The company assumes no
liability whatsoever to update these forward-looking statements or to conform
them to future events or developments.
SOURCE Bayer HealthCare Pharmaceuticals Inc.
