asiapulse

http://au.biz.yahoo.com//070905/17/1dthf.html

Wednesday September 5, 11:58 AM

DATA AFFIRMS BENEFIT OF ALIMTA FOR

(Full text of a statement. Contact details follow below.)

DATA AFFIRM BENEFIT OF ALIMTA(R) (PEMETREXED FOR INJECTION) FOR PATIENTS WITH MALIGNANT PLEURAL MESOTHELIOMA SEOUL, Sept. 4 /PRNewswire-AsiaNet/ --

ALIMTA-based Regimens Continue to Support Patients with Devastating Disease

Data from two large, open-label studies show patients experienced one-year survival rates above 50 percent when treated with ALIMTA(R) (pemetrexed for injection) or ALIMTA-based regimens for malignant pleural mesothelioma (MPM) in both a first-line and second-line setting. The study results affirm important efficacy and safety benefits for Eli Lilly and Company's ALIMTA, the only-known agent to demonstrate a survival benefit in this often difficult-to-treat disease primarily associated with exposure to asbestos. The data were presented today at the 12th World Conference on Lung Cancer.

One of the largest studies undertaken in the treatment of mesothelioma, the triple-arm, open-label, multicenter, first-line study (WCLC Abstract # C5-01) treated patients with ALIMTA as a single agent, while the other two arms evaluated ALIMTA in combination with either cisplatin or carboplatin. All three arms demonstrated clinically similar one-year survival rates (58.6% for ALIMTA alone; 63.1% for ALIMTA+cisplatin, and; 64.0% for ALIMTA+carboplatin). The ALIMTA plus platinum combination arms achieved higher response rates than ALIMTA alone (10.5% for ALIMTA; 26.3% for ALIMTA+cisplatin, and; 21.7% for ALIMTA+carboplatin). All 2,023 patients treated in the first-line setting had a histologic or cytologic diagnosis (pa-tients cells were reviewed under a microscope) of MPM that was not amenable to curative surgery.

An open-label, multicenter study (WCLC Abstract # C5-03), evaluated the results from 988 patients who were treated in a second-line setting for MPM with ALIMTA as a single agent, ALIMTA+cisplatin or ALIMTA+carboplatin after being previously treated with chemotherapy. All three arms demonstrated a significant one-year survival rate (54.7% for ALIMTA alone; 67.9% for ALIMTA+cisplatin, and; 65.5% for ALIMTA+carboplatin). Patients treated with ALIMTA in combination with a platinum-based chemotherapy demonstrated higher response rates (12.1% for ALIMTA; 23.8% for ALIMTA+cisplatin, and; 16.8% for ALIMTA+carboplatin). The most common grade 3/4 toxicities on both studies were leukopenia, neutropenia, thrombocytopenia and anemia.

"The initial clinical trial results for ALIMTA in malignant pleural mesothelioma were definitely considered a medical breakthrough when they were unveiled just three years ago," said Richard Gaynor, M.D., vice president, cancer research and global oncology platform leader for Lilly. "It is encouraging that these open-label studies show real world patient treatment outcomes that are consistent with those from the controlled clinical research environment. In my opinion, this is clinically meaningful information to the practicing oncologist."

ALIMTA was approved by both the European Medicines Agency (EMEA) and the U.S. Food and Drug Administration (FDA) in 2004 in combination with cisplatin for the treatment of MPM. To date, ALIMTA has been approved in more than 85 countries in combination with cisplatin for the treatment of MPM.

Mesothelioma

Malignant pleural mesothelioma is a rare cancer of the lining of the lungs. The disease is often associated with asbestos exposure and has a long latency period -- usually between 20 and 40 years. Most people are not diag-nosed until the cancer is in advanced stages and treatment with surgery or ra-diation is not an option.

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 500 mg/m2 of body surface area (BSA), given by ten-minute infusion, on day 1 of each 21-day cycle. Cisplatin is used at 75 mg/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 cis-platin treatment must be given.

Non-small cell lung cancer: The recommended dose of pemetrexed is 500 mg/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 de-tails 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, in-cluding a differential white cell count and platelet count. Absolute neutro-phil 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 tox-icity, neurotoxicity, and/or impaired hepatic/renal function. (For full in-formation 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 45 ml/min require no dose adjustment other than those recommended for all patients. Use in patients with creatinine clearance below 45 ml/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 se-verity of skin reactions. Serious renal events, including acute renal failure, have been reported with pemetrexed alone or in combination with other chemo-therapeutic agents. Many of the patients in whom these occurred had underly-ing risk factors including dehydration or pre-existing hypertension or diabe-tes. 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 cardio-vascular risk. Concomitant use of live attenuated vaccines is not recom-mended.

Interactions

Concomitant administration of nephrotoxic drugs and substances that are also tubularly secreted could potentially result in delayed clearance of pe-metrexed. 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 re-nal function (creatinine clearance greater than or equal to 80 ml/min), high doses of NSAIDs (such as ibuprofen >1600 mg/day) and aspirin at higher dosage (greater than or equal to 1.3 g daily) may decrease pemetrexed elimination and increase the occurrence of adverse events. Patients with mild to moderate re-nal insufficiency (creatinine clearance from 49 to 79 ml/min) should avoid taking NSAIDs (e.g., ibuprofen) or aspirin at higher dosage, for 2 days be-fore, on the day of, and 2 days following pemetrexed administration.

There is a possible interaction between oral anticoagulants and pe-metrexed; 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 fa-ther 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, neu-tropenia. Common: Febrile neutropenia and infection without neutropenia. Un-common: 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, in-creased GGT. Rare: Cases of hepatitis, potentially serious, have been re-ported 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, an-gina pectoris, cerebrovascular accident, arrhythmias, transient ischaemic at-tack. (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 pro-grams 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 ap-plying the latest research from its own worldwide laboratories and from col-laborations with eminent scientific organizations. Headquartered in Indianapo-lis, 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 malignant pleural mesothelioma 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 un-dertakes no duty to update forward-looking statements.

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

SOURCE: Eli Lilly and Company

CONTACT: Gregory L. Clarke,

Lilly,

+1-317-554-7119 (mobile), or

gregory.clarke@lilly.com, or

Chantal Samonte,

CPR Worldwide,

+1-202-550-4129 (mobile),

c.samonte@cprworldwideusa.com

Photo: NewsCom:

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

PRN Photo Desk:

photodesk@prnewswire.com (LLY)

ASIA PULSE