Data Affirm Benefit of ALIMTA(R) (pemetrexed for injection) for Patients with Non-Small Cell Lung Cancer

Data Affirm Benefit of ALIMTA(R) (pemetrexed for injection) for Patients with Non-Small Cell Lung Cancer

September 04, 2007

    SEOUL, South Korea, Sept. 3 /Xinhua-PRNewswire/ -- 

    The clinical benefit of ALIMTA(R) (pemetrexed for
injection) continues to be validated across patient
populations, as demonstrated in two studies conducted in
Asia.  The data presented today at the 12th World
Conference on Lung Cancer provide further support of the
efficacy of Eli Lilly and Company's ALIMTA in treating
non-small cell lung cancer (NSCLC), the world's most common
form of cancer.(1) ALIMTA is currently indicated for the
second-line treatment of non small cell lung cancer in more
than 85 countries.

    In one study (WCLC Abstract # P2-274), a Japanese
multicenter, randomized Phase II trial, pretreated patients
with locally advanced or metastatic NSCLC demonstrated more
than 12 months of median survival time when treated with
ALIMTA.  

    "This is data showing that ALIMTA not only
provides excellent outcomes but also a favorable quality of
life in pretreated patients with non-small cell lung
cancer," said Dr. Kaoru Kubota, M.D., of the National
Cancer Center Hospital East in Kashiwa, Japan and the
study's principal investigator.  "Other Western
studies have demonstrated similar efficacy of ALIMTA in
patients with non-small cell lung cancer. It is nice to see
clinical benefits substantiated in Japanese patients and
observe consistency in the drug's performance."

    The study evaluated 216 patients, comparing the current
approved dose of ALIMTA 500 mg/m2 to ALIMTA 1000 mg/m2. 
Patients in the 500 mg/m2 arm showed a median survival time
of 16 months compared to 12.6 months for patients in the
1000 mg/m2 arm.  The study also showed one-year survival
rates of 59.2 percent and 53.7 percent, and response rates
of 18.5 percent and 14.8 percent, respectively. The study
also provides supporting information for oncologists,
affirming the currently approved dose of ALIMTA as the
proper dosage for use in the second-line treatment of
NSCLC.

    Additionally, a randomized Phase II Taiwanese study
(WCLC Abstract # P2-245) showed a median survival time of
9.1 months in patients with NSCLC who were treated either
in the second- or third-line setting.  The study involved
44 patients who had failed previous treatment with
platinum-based chemotherapies with/without tyrosine-kinase
treatment.  An overall response rate of 18.2 percent was
achieved with a response rate of 40 percent in patients
treated in second-line compared to 11.8 percent in
third-line or later treatment patients.  The study also
found that treatment toxicities tended to be generally
mild.  Grade 3/4 hematological toxicities included
neutropenia in 18.2 percent, thrombocytopenia in 6.8
percent and anemia in 4.5 percent.  Non-hematological
toxicities were all less than grade 3.

    Three additional studies (WCLC Abstract # P2-226, WCLC
Abstract # P2-237, WCLC Abstract # P2-243) being presented
at WCLC also provided further affirming evidence of the
efficacy of ALIMTA in the second-line treatment of NSCLC.

    "We have always been impressed with ALIMTA for its
consistent performance and versatility," said Richard
Gaynor, M.D., vice president, cancer research and global
oncology platform leader for Lilly.  "These studies
underline the efficacy of ALIMTA in the second-line
treatment of non-small cell lung cancer.  As Lilly looks to
potentially bring ALIMTA to market in countries throughout
Asia, it is important that ALIMTA demonstrates efficacy and
safety across diverse patient populations." 

    ALIMTA, as a single agent, was approved by both the
European Medicines Agency (EMEA) and the U.S. Food and Drug
Administration (FDA) in 2004 for the second-line treatment
of NSCLC.

    About Non-Small Cell Lung Cancer (NSCLC)

    NSCLC is the most common type of lung cancer and
represents 75-80 percent of all lung cancers.  NSCLC has
five-tier staging, starting at 0 and rising to the severity
of stage IV.  NSCLC can spread through the lymphatic system,
penetrating the chest lining, ribs, and the nerves and blood
vessels that lead to the arm.  The liver, bones and brain
are potential targets if the cancerous cells enter the
blood stream.

    (1) Parkin DM, Bray F, Ferlay J, Pisani P, Global
Cancer Statistics, 2002. 
        CA Cancer J Clin 2005;55;74-108,
       
http://intl-caonline.amcancersoc.org/cgi/content/abstract/55/2/74,

        (April 10, 2007).

    ALIMTA ABBREVIATED PRESCRIBING INFORMATION

    Uses

    ALIMTA is indicated in combination with cisplatin for
the treatment of chemotherapy naive patients with
unresectable malignant pleural mesothelioma.  ALIMTA is
indicated as monotherapy for the treatment of patients with
locally advanced or metastatic non-small cell lung cancer,
after prior chemotherapy.

    Dosage and Administration

    The drug is to be administered intravenously, under the
supervision of a physician qualified in the use of cytotoxic
anti-cancer therapy.

    Malignant pleural mesothelioma: Pemetrexed in
combination with cisplatin has been investigated using a
three-week (21-day) cycle.  Pemetrexed is used at 500mg/m2
of body surface area (BSA), given by ten-minute infusion,
on day 1 of each 21-day cycle.  Cisplatin is used at
75mg/m2 BSA, given by two-hour infusion, approximately 30
minutes after completion of the pemetrexed infusion on day
1 of each cycle.  Adequate anti-emetic treatment and
hydration for cisplatin treatment must be given.

    Non-small cell lung cancer: The recommended dose of
pemetrexed is 500mg/m2 BSA, given by ten-minute infusion,
on day 1 of each 21-day cycle.

    Pre-medication: Supplement with 1000 micrograms
intramuscular vitamin B12 and oral folic acid (350 to 1000
micrograms) to reduce toxicity (for full details see
Summary of Product Characteristics [SPC]).  To reduce the
incidence and severity of skin reactions, a corticosteroid
should be given the day prior to, on the day of, and the
day after pemetrexed administration - this should be
equivalent to 4mg of dexamethasone administered orally
twice a day.

    Monitoring: Monitor prior to each dose for complete
blood cell count, including a differential white cell count
and platelet count.  Absolute neutrophil count should be
greater than or equal to 1,500 cells/mm3 and platelets
greater than or equal to 100,000 cells/mm3.  Prior to each
dose, collect blood chemistry tests to evaluate renal and
hepatic function.  Dose adjustments to pemetrexed and/or
cisplatin at the start of a subsequent cycle should be
based on nadir haematological counts or maximum
non-haematological toxicity.  If necessary, delay or
withhold treatment in the presence of haematological
toxicity, neurotoxicity, and/or impaired hepatic/renal
function.  (For full information on dose modification see
SPC.)
    
    Children and adolescents: Not recommended for use in
patients under 18 years of age.

    Renal impairment: Patients with creatinine clearance
greater than or equal to 45ml/min require no dose
adjustment other than those recommended for all patients. 
Use in patients with creatinine clearance below 45ml/min is
not recommended.  See also Warnings and Special
Precautions.

    Hepatic impairment: Patients with hepatic impairment,
such as bilirubin >1.5-times the upper limit of normal
and/or transaminase >3.0-times the upper limit of normal
(hepatic metastases absent) or >5.0-times the upper limit
of normal (hepatic metastases present), have not been
specifically studied.

    Contra-indications

    Hypersensitivity to pemetrexed or to any of the
excipients.  Concomitant yellow fever vaccine. 
Breast-feeding.

    Warnings and Special Precautions

    Myelosuppression is usually the dose-limiting toxicity.
 Patients must be instructed to take folic acid and vitamin
B12 as a prophylactic measure.  Pre-treatment with
dexamethasone (or equivalent) can reduce the incidence and
severity of skin reactions. Serious renal events, including
acute renal failure, have been reported with pemetrexed
alone or in combination with other chemotherapeutic agents.
 Many of the patients in whom these occurred had underlying
risk factors including dehydration or pre-existing
hypertension or diabetes.  In patients with clinically
significant third space fluid, consideration should be
given to draining the effusion prior to administration. 
Serious cardiovascular events, including myocardial
infarction and cerebrovascular events, have been uncommonly
reported when pemetrexed is given in combination with other
cytotoxic agents; most of these patients had pre-existing
cardiovascular risk.  Concomitant use of live attenuated
vaccines is not recommended.
  
    Interactions

    Concomitant administration of nephrotoxic drugs and
substances that are also tubularly secreted could
potentially result in delayed clearance of pemetrexed.  If
necessary, creatinine clearance should be closely
monitored.  Patients must avoid taking non-steroidal
anti-inflammatory drugs (NSAIDs) with long elimination
half-lives for at least 5 days prior to, on the day, and at
least 2 days following pemetrexed administration.  In
patients with normal renal function (creatinine clearance
greater than or equal to 80ml/min), high doses of NSAIDs
(such as ibuprofen >1600mg/day) and aspirin at higher
dosage (greater than or equal to 1.3g daily) may decrease
pemetrexed elimination and increase the occurrence of
adverse events.  Patients with mild to moderate renal
insufficiency (creatinine clearance from 49 to 79ml/min)
should avoid taking NSAIDs (e.g., ibuprofen) or aspirin at
higher dosage, for 2 days before, on the day of, and 2 days
following pemetrexed administration.

    There is a possible interaction between oral
anticoagulants and pemetrexed; therefore, increase the
frequency of International Normalised Ratio monitoring
(INR) if treating with oral anticoagulants.

    Pregnancy and Lactation

    Avoid in pregnancy and do not use in breast-feeding
women.
    
    Pemetrexed can be genotoxic; sexually mature males are
advised not to father a child during treatment and up to 6
months thereafter.  Owing to the possibility of
irreversible infertility, men are advised to seek
counselling on sperm storage before starting treatment. 
Women of childbearing potential must use effective
contraception during treatment.

    Driving, etc

    It has been reported that pemetrexed can cause
somnolence.  Patients should be cautioned against driving
or operating machinery.

    Undesirable Effects

    Haematological: Very common: Anaemia, leucopenia,
thrombocytopenia, neutropenia.  Common: Febrile neutropenia
and infection without neutropenia.  Uncommon: Pancytopenia.

    Gastro-intestinal: Very common: Nausea, vomiting,
stomatitis/pharyngitis, anorexia, diarrhoea, constipation. 
Common: Dyspepsia, abdominal pain.  Rare: Colitis.

    General: Very common: Fatigue.  Common: Fever,
conjunctivitis.

    Metabolism and nutrition: Common: Dehydration.

    Nervous system: Very common: Neuropathy - sensory. 
Common: Neuropathy - motor, dysgeusia.

    Renal and urinary: Very common: Creatinine elevation,
creatinine clearance decreased.  Common: Renal failure.

    Hepatobiliary: Common: SGPT (ALT) elevation and SGOT
(AST) elevation, increased GGT.  Rare: Cases of hepatitis,
potentially serious, have been reported during trials.

    Skin and subcutaneous tissue: Very common:
Rash/desquamation, alopecia.  Common: Urticaria, allergic
reaction/hypersensitivity, erythema multiforme, pruritus.

    Cardiovascular and cerebrovascular: Uncommon:
Myocardial infarction, angina pectoris, cerebrovascular
accident, arrhythmias, transient ischaemic attack. 
(Usually when given in combination with other cytotoxic
agents and with pre-existing cardiovascular risk.)  Common:
Chest pain.

    For full details of these and other side-effects,
please see the Summary of Product Characteristics, which is
available at http://emc.medicines.org.uk/.

    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.  
 
    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

    This press release contains forward-looking statements
about the potential of ALIMTA for the treatment of
non-small cell lung cancer and reflects Lilly's current
beliefs.  However, as with any pharmaceutical products
under development, there are substantial risks and
uncertainties in the process of development,
commercialization, and regulatory review.  There is no
guarantee that the products will receive additional
regulatory approvals. There is also no guarantee that the
products will continue to be commercially successful.  For
further discussion of these and other risks and
uncertainties, see Lilly's filings with the United States
Securities and Exchange Commission.  Lilly undertakes no
duty to update forward-looking statements.

    ( Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO)


    For more information, please contact:

     Gregory L. Clarke 
     Lilly 
     Phone: [phone] (mobile)
     Email: [e-mail]

     Chantal Samonte
     CPR Worldwide
     Phone: [phone] (mobile)
     Email: [e-mail]