Study Supports Activity of GEMZAR(R) (Gemcitabine HC1 for Injection) in the Treatment of Early-Stage Breast Cancer

Study Supports Activity of GEMZAR(R) (Gemcitabine HC1 for Injection) in the Treatment of Early-Stage Breast Cancer

June 04, 2007

Five Phase III Early-Stage Breast Cancer Studies Underway
With GEMZAR


    CHICAGO, June 4 /Xinhua-PRNewswire/ -- 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-Meyers 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)


    For more information, please contact:

     Gregory L. Clarke 
     Lilly
     Tel:    [phone]
     Mobile: [phone]
     Email:  [e-mail]

     Neil Hochman
     CPR Worldwide
     Tel:    [phone]
     Mobile: [phone]
     Email:  [e-mail]