Study Supports Activity of GEMZAR(R) (Gemcitabine HC1 for Injection) in the Treatment of Early-Stage Breast Cancer
June 02 2007 - 4:00PM
PR Newswire (US)
Five Phase III Early-Stage Breast Cancer Studies Underway With
GEMZAR CHICAGO, June 2 /PRNewswire-FirstCall/ -- GEMZAR(R)
(gemcitabine HC1 for injection), approved in combination with
paclitaxel (Taxol(R)) in the first- line, post-surgical treatment
of metastatic breast cancer, was the subject of a study presented
today with encouraging results in the pre-surgical treatment of
breast cancer. The study was presented at the 43rd Annual Meeting
of the American Society of Clinical Oncology (ASCO). Results showed
that adding GEMZAR to the current standard-of-care treatment was a
promising regimen for patients with stage II-III breast cancer. Eli
Lilly and Company, the manufacturer and marketer of GEMZAR, also
cited five completed or ongoing Phase III trials which will further
study GEMZAR as a chemotherapeutic foundation for the treatment of
early-stage breast cancer. Today's Phase II study (Abstract #
595(i)) evaluated the addition of GEMZAR to the current
standard-of-care of epirubicin and cyclophosphamide followed by
paclitaxel in patients with stage II-III breast cancer. The
treatment schedule was a dose-dense sequential neoadjuvant
(pre-surgical) chemotherapy combination, meaning that the
combination was administered at shorter intervals between
treatments. Results showed a promising regimen in terms of
pathologic complete response (pCR-the absence of invasive tumor in
the breast). In addition, patients who tested positive for the
HER-2 gene also were given trastuzumab (Herceptin(R)) and
demonstrated additional response. "The data released today reflects
our ongoing, aggressive research plan involving GEMZAR as a key
therapeutic foundation for the treatment of breast cancer," said
Allen Melemed, M.D., medical director, global oncology at Lilly.
"We are encouraged with the activity GEMZAR has shown in this
breast cancer study." Enrollment has been completed in one trial,
and is ongoing in an additional four, Phase III early-stage breast
cancer studies evaluating the addition of GEMZAR to commonly-used
treatment regimens. Two adjuvant (post- surgical) therapy trials,
NSABP B-38 (4,400 patients) and TANGO (3,000 patients), will
compare the addition of GEMZAR to the paclitaxel arm of each study.
A third adjuvant trial, SUCCESS (3,600 patients), will compare the
addition of GEMZAR to a docetaxel-based regimen. Two additional
trials, which are neoadjuvant specific, NSABP B-40 (1,200 patients)
and Neo-TANGO (800 patients), will evaluate the addition of GEMZAR
to the paclitaxel or docetaxel arm of the treatment regimen. For
more information on these studies, log on to
http://www.lillytrials.com/ or http://www.clinicaltrials.gov/. More
About ASCO Abstract # 595 The trial enrolled stage II-III breast
cancer patients (with a median age of 45), including inflammatory
tumors, a type of breast cancer that causes the breast to swell,
redden and feel warm. Of the 73 patients enrolled in the study, 42
(57.5%) were classified as T2; 12 (16.5%) as T3, and; 19 (26%) as
T4, which included 13 patients with inflammatory tumors. A
T-classification represents the stage of the tumor with T4 being
the most advanced. A biopsy was performed before treatment for the
biomarker component of the study. Patients received a first
sequence of epirubicin and cyclophosphamide (90/600 mg/m squared)
for three cycles followed by a second sequence of paclitaxel and
GEMZAR (150/2500 mg/m squared) for six cycles. Treatment was
administered on day one, every two weeks, with growth factor
support. HER-2 positive patients (20 patients, 27.3%), were given
trastuzumab (2 mg/kg with a loading dose 4 mg/kg) concomitantly.
Afterward, the patients underwent surgery, radiotherapy and
adjuvant hormonal therapy according to institutional practice. All
patients from the study showed response to the regimen. Of the
entire study group, 27 (36.9%) patients achieved a pCR (absence of
invasive tumor in the breast), with 50% representation from the
HER-2 positive patients who also were given trastuzumab.
Forty-seven patients (64.4%) underwent conservative surgery. The
grade 3/4 hematological toxicities were: leukopenia in six patients
(9%); neutropenia (a decrease in white blood cells) in eight
patients (12%), and; anemia (a decrease in red blood cells) in one
(2%). Nausea (13%) and vomiting (15%) were the most frequent grade
3/4 non-hematological toxicities. Asymptomatic decrease in cardiac
ejection fraction was observed in one patient treated with
trastuzumab with subsequent normalization. About Breast Cancer
Breast cancer is the most common form of cancer among women,
affecting nearly one out of every eight women.(ii) The disease is
diagnosed in more than 1.1 million women worldwide each year.(iii)
Breast cancer progresses in stages based on tumor size, how the
cancer affects the lymph nodes and whether it has metastasized to
other parts of the body.(iv) In general, individuals with earlier
stages of disease have better chances for long-term survival and
recovery. GEMZAR Indications GEMZAR in combination with paclitaxel
is indicated for the first-line treatment of patients with
metastatic breast cancer after failure of prior
anthracycline-containing adjuvant chemotherapy, unless
anthracyclines were clinically contraindicated. GEMZAR is indicated
in combination with cisplatin for the first-line treatment of
patients with inoperable, locally advanced (stage IIIA or IIIB), or
metastatic (stage IV) non-small cell lung cancer. GEMZAR is
indicated as first-line treatment for patients with locally
advanced (nonresectable stage II or stage III) or metastatic (stage
IV) adenocarcinoma of the pancreas. GEMZAR is indicated for
patients previously treated with 5-FU. GEMZAR in combination with
carboplatin is indicated for the treatment of patients with
advanced ovarian cancer that has relapsed at least 6 months after
completion of platinum-based therapy. Important Safety Information
for GEMZAR Myelosuppression is usually the dose-limiting toxicity
with GEMZAR therapy. Contraindication Known hypersensitivity to
GEMZAR. Anaphylactoid reaction has been reported rarely. Warnings
Infusion times of GEMZAR longer than 60 minutes and more frequent
than weekly dosing have been shown to increase toxicity. Pulmonary
toxicity has been reported with the use of GEMZAR. In cases of
severe lung toxicity, GEMZAR therapy should be discontinued
immediately and appropriate supportive care measures instituted.
Hemolytic Uremic Syndrome (HUS) and/or renal failure have been
reported following one or more doses of GEMZAR. Renal failure
leading to death or requiring dialysis, despite discontinuation of
therapy, has been rarely reported. The majority of the cases of
renal failure leading to death were due to HUS. Serious
hepatotoxicity, including liver failure and death, has been
reported very rarely in patients receiving GEMZAR alone or in
combination with other potentially hepatotoxic drugs. GEMZAR is
Pregnancy Category D. GEMZAR can cause fetal harm when administered
to a pregnant woman. Precautions Use caution in patients with
pre-existing renal impairment or hepatic insufficiency.
Administration of GEMZAR may exacerbate underlying hepatic
insufficiency. The optimum regimen for safe administration of
GEMZAR with therapeutic doses of radiation has not yet been
determined in all tumor types. GEMZAR has radiosensitizing activity
and radiation recall reactions have been reported. It is not known
whether GEMZAR or its metabolites are excreted in human milk. The
effectiveness of GEMZAR in pediatric patients has not been
demonstrated. The toxicities of GEMZAR observed in pediatric
patients were similar to those reported in adults. GEMZAR clearance
is affected by age as well as gender. Patients receiving therapy
with GEMZAR should be monitored closely by a physician experienced
in the use of cancer chemotherapeutic agents. Monitoring and Dosage
Modifications Dosage adjustments for hematologic toxicity may be
required. Serum creatinine, potassium, calcium, and magnesium
should be monitored during combination therapy with cisplatin.
Patients should be assessed with a CBC, including differential and
platelet count, prior to each dose of GEMZAR. Modify or suspend
therapy according to the Dosage Reduction Guidelines in the full
Prescribing Information. Hepatic and renal function (including
transaminases and serum creatinine) should be evaluated prior to
therapy with GEMZAR and periodically thereafter. Adverse Events The
most severe adverse events (grades 3/4) with GEMZAR plus paclitaxel
for the treatment of patients with MBC were neutropenia (48%);
alopecia (18%); leukopenia (11%); anemia (7%); fatigue (7%);
thrombocytopenia (6%); ALT elevation (6%); and neuropathy-sensory
(6%). The most common adverse events (all grades) were nausea
(50%); fatigue (40%); myalgia (33%); and vomiting (29%). The most
severe adverse events (grades 3/4) with GEMZAR for the first- line
treatment of patients with pancreatic cancer were neutropenia
(24%-26%); alkaline phosphatase elevation (16%-20%); AST elevation
(12%-17%); nausea/vomiting (12%-13%); ALT elevation (10%-11%);
anemia (10%); leukopenia (9%-10%); thrombocytopenia (8%-10%);
bilirubin elevation (4%-8%); and pain (2%-7%). The most common
adverse events (all grades) were AST (72%-78%); alkaline
phosphatase (71%-77%); anemia (65%-73%); ALT (72%); leukopenia
(64%- 71%); nausea and vomiting (64%-71%); neutropenia (61%-62%);
thrombocytopenia (36%-47%); pain (10%-42%); fever (30%-38%);
proteinuria (10%-32%); constipation (10%-31%); diarrhea (24%-30%);
rash (24%-28%); and bilirubin (16%-26%). The most severe adverse
events (grades 3/4) with GEMZAR plus cisplatin for the first-line
treatment of patients with NSCLC were neutropenia (57%-64%);
thrombocytopenia (50%-55%); leukopenia (29%-46%); anemia (22%-25%);
nausea (27%); vomiting (23%); nausea/vomiting (39%); neuromotor
(12%); hypomagnesemia (7%); neurohearing (6%); creatinine elevation
(5%); alopecia (1%-13%); and dyspnea (1%-7%). The most common
adverse events (all grades) were paresthesias (38%); hyperglycemia
(30%); infection (18%-28%); and constipation (17%-28%). The most
severe adverse events (grades 3/4) with GEMZAR plus carboplatin for
the treatment of patients with advanced ovarian cancer were
neutropenia (71%), thrombocytopenia (35%), leukopenia (53%), anemia
(28%), nausea (6%), vomiting (6%), and constipation (7%). The most
common adverse events (all grades) were RBC transfusion (38%),
alopecia (49%), neuropathy/sensory (29%), nausea (69%), fatigue
(40%), vomiting (46%), diarrhea (25%), and constipation (42%). See
complete Warnings, Precautions, Adverse Reactions, and Dosage and
Administration sections in the accompanying full Prescribing
Information for safety and dosing guidelines. About Lilly Oncology,
a Division of Eli Lilly and Company For more than four decades,
Lilly Oncology has been collaborating with cancer researchers to
deliver innovative treatment choices and valuable programs to
patients and their physicians. Inspired by courageous patients
living with cancer, Lilly Oncology is providing treatments that are
considered global standards of care and developing a broad
portfolio of novel targeted therapies to accelerate the pace and
progress of cancer care. To learn more about Lilly's commitment to
cancer, please visit http://www.lillyoncology.com/. About Eli Lilly
and Company Lilly, a leading innovation-driven corporation, is
developing a growing portfolio of first-in-class and best-in-class
pharmaceutical products by applying the latest research from its
own worldwide laboratories and from collaborations with eminent
scientific organizations. Headquartered in Indianapolis, Ind.,
Lilly provides answers - through medicines and information - for
some of the world's most urgent medical needs. P-LLY ALIMTA(R)
(pemetrexed for injection), Lilly GEMZAR(R) (gemcitabine HCl for
injection), Lilly Taxol(R) (paclitaxel), Bristol-Myers Squibb
Herceptin(R) (trastuzumab), Genentech This press release contains
forward-looking statements about the potential of GEMZAR for the
treatment of breast cancer and reflects Lilly's current beliefs.
However, as with any pharmaceutical product under development,
there are substantial risks and uncertainties in the process of
development, commercialization, and regulatory review. There is no
guarantee that the product will receive additional regulatory
approvals. There is also no guarantee that the product will
continue to be commercially successful. For further discussion of
these and other risks and uncertainties, see Lilly's filing with
the United States Securities and Exchange Commission. Lilly
undertakes no duty to update forward-looking statements. (i)
Sanchez-Munoz A, Duenos-Garcia R, et al. Neoadjuvant chemotherapy
with a dose-dense sequential combination of epirubicin and
cyclophosphamide followed by paclitaxel and gemcitabine +/-
trastuzumab in stage II and III breast cancer. Correlation between
pathologic complete response and biologic markers. Abstract #595,
American Society of Clinical Oncology (ASCO) Annual Meeting 2007.
(ii) American Cancer Society, "What Are the Key Statistics for
Breast Cancer?," American Cancer Society, http://www.cancer.org/,
(May 2, 2007). (iii) Pan American Health Organization, "Guidelines
for International Breast Health and Cancer Control,"
http://www.paho.org/, (March 21, 2006). (iv) American Cancer
Society, "How is Breast Cancer Staged?," American Cancer Society,
http://www.cancer.org/ (February 28, 2007). (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO)
http://www.newscom.com/cgi-bin/prnh/20070602/CLSA001 DATASOURCE:
Eli Lilly and Company CONTACT: Gregory L. Clarke, Lilly,
+1-317-276-5222 (office), +1-317-554-7119 (mobile), ; or Neil
Hochman, CPR Worldwide, +1-212-453-2067 (office), +1-516-784-9089
(mobile),
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