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Monday 21st February, 2005
FDA has granted full approval to DOXIL® for the treatment of ovarian cancer
that has progressed or recurred after platinum-based chemotherapy.
Bridgewater, N.J. ? February 7, 2005 -- The U.S. Food and Drug
Administration (FDA) has granted full approval to DOXIL? (doxorubicin
HCl liposome injection) for the treatment of patients with ovarian
cancer whose disease has progressed or recurred after platinum-based
DOXIL, marketed in the United States by Tibotec Therapeutics,
Division of Ortho Biotech Products, L.P., originally received
accelerated approval for refractory ovarian cancer in June 1999. As a
result of the full approval, the product label for DOXIL has been
updated to include survival, time to disease progression and tumor
response rate data from a randomized Phase III clinical study.
Under accelerated approval, DOXIL was indicated for the treatment of
metastatic ovarian cancer in patients with disease that was refractory
to both paclitaxel- and platinum-based chemotherapy regimens. This
approval was based on tumor response rates from three Phase II studies.
According to the terms of the accelerated approval, Johnson & Johnson
Pharmaceutical Research & Development, L.L.C. (J&JPRD) completed a
randomized Phase III clinical study to formally demonstrate the drug's
clinical benefit in patients with relapsed ovarian cancer. In March
2004, J&JPRD submitted a supplemental new drug application (sNDA) based
on data from the Phase III study.
"The Phase III data provide evidence of the product's clinical
benefit for patients with relapsed ovarian cancer," commented Alan N.
Gordon, M.D., of the University of Arizona School of Medicine and
Arizona Gynecologic Oncology, in Phoenix, Ariz., and lead author of the
Phase III study, known as DOXIL Study 30-49.
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In the randomized, multi-center, open-label, Phase III study, 474
patients with recurrent epithelial ovarian cancer were randomly assigned
to receive either DOXIL 50 mg/m2 every 28 days or topotecan HCl 1.5
mg/m2/day for five consecutive days every 21 days. A total of 239
patients received DOXIL; 235 patients received topotecan HCl. The
primary endpoint, time to disease progression after starting therapy,
was comparable for the two treatment groups. The median time to disease
progression was 4.1 months for the DOXIL group and 4.2 months for the
topotecan HCl group; the p value, a statistical measurement, was 0.617.
The overall median survival was 14.4 months for patients treated with
DOXIL and 13.7 months for patients treated with topotecan HCl; the p
value was 0.05. The p value was not adjusted for multiple comparisons.
The overall tumor response rate for DOXIL-treated patients was 19.7
percent and 17 percent for topotecan-treated patients. The Phase III
data were published in the September 2001 issue of the Journal of
Clinical Oncology and in the October 2004 issue of the journal
DOXIL is indicated for the treatment of patients with ovarian cancer
whose disease has progressed or recurred after platinum-based
Myocardial damage may lead to congestive heart failure and may be
encountered as the total cumulative dose of doxorubicin HCl approaches
550 mg/m2. The use of DOXIL may lead to cardiotoxicity. DOXIL should be
administered to patients with a history of cardiovascular disease only
when the benefit outweighs the risk. Acute infusion-associated reactions
have occurred in up to 10 percent of patients treated with DOXIL.
Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like
infusion reactions have been reported. Medications to treat such
reactions, as well as emergency equipment, should be available for
immediate use. Severe myelosuppression may occur. Dosage should be
reduced in patients with impaired hepatic function. Accidental
substitution of DOXIL for doxorubicin HCl has resulted in severe side
effects. DO NOT SUBSTITUTE. The use of DOXIL should be limited to
physicians experienced in the use of cancer chemotherapeutic agents.
In clinical studies in recurrent ovarian cancer, the most common side
effects reported with DOXIL therapy included hand-foot syndrome, nausea,
mouth sores (stomatitis), tiredness, abdominal pain, vomiting,
constipation, rash, fever, reduced red blood cell count (anemia),
reduced white blood cell count (neutropenia), weakness, hair loss,
appetite loss and diarrhea. Some patients experienced infusion-related
reactions and skin reactions. Hand-foot syndrome, also known as palmar-plantar
erythrodysesthesia (PPE), is characterized by symptoms of swelling,
pain, redness and, for some patients, peeling of the skin on the hands
and feet; in 23 percent of patients, these symptoms were severe. In some
patients enrolled in DOXIL clinical trials, heart-related side effects
were reported, some of which were severe. Due to the serious,
potentially permanent effects of some of these events, including the
potential for bone marrow suppression, close monitoring is necessary.
About Ovarian Cancer
Ovarian cancer is the most deadly form of gynecologic cancer.
According to the American Cancer Society, an estimated 22,220 American
women are expected to be diagnosed with ovarian cancer in 2005 and more
than 16,000 of these women are expected to die from the disease. The
Ovarian Cancer National Alliance reports that approximately 50 percent
of women diagnosed with ovarian cancer die from it within five years.
However, nearly 75 percent of ovarian cancer cases are diagnosed in
later stages when the disease is more difficult to treat and the chance
of five-year survival is only about 25 percent.