Due to the revolutionary impact Alimta (pemetrexed) has had on the Mesothelioma treatment, we have decided to dedicate a separate page that will follow all the new developments regarding the trials and usage of Alimta. Just click on one of the links below that will take you to the Alimta-related article.

FDA Approves Alimta-Cisplatin Combination For Treatment of Asbestos-Related Cancer (February-05-2003)

Alimta vs. Taxotere - Similar Survival, Fewer Side Effects In Recurrent Non-Small Cell Lung Cancer (June-01-2003)

Lung cancer drug Alimta has fewer side effects (June-02-2003)

INDIANAPOLIS, IN -- February 5, 2004 -- The first and only drug regimen proven to help patients with an asbestos-related cancer live longer was approved today by the U.S. Food and Drug Administration.

Alimta® ("uh-LIMB-ta"), to be introduced shortly by Eli Lilly and Company (NYSE: LLY), was approved for use with cisplatin, a standard chemotherapy agent, for the treatment of malignant pleural mesothelioma, a cancer of the lining of the lungs, in patients who are not candidates for surgery. Malignant pleural mesothelioma is "one of the most devastating kinds of cancer a person can have," said Paolo Paoletti, M.D., vice president of oncology clinical research at Lilly. "This is a cancer that is lethal, painful and debilitating."

Estimates are between 10,000 and 15,000 people worldwide are diagnosed annually with malignant pleural mesothelioma, a figure that is increasing. Most people do not learn they have malignant pleural mesothelioma until the disease has progressed to an advanced stage when treatment with surgery or radiation is not an option.

Finding an active drug treatment has proved long and difficult. "Throughout the 1970s, '80s and really the '90s, we tried a host of different drugs. I was involved in many of these trials and most of them had virtually no effect on the cancer," said Nicholas Vogelzang, M.D., who led the global Phase III clinical trial evaluating Alimta/cisplatin while director of the University of Chicago Cancer Research Center. (On Jan. 2, 2004, Dr. Vogelzang became director of the Nevada Cancer Institute in Las Vegas.)

Alimta/cisplatin proved different. This drug regimen was compared to cisplatin alone in a trial of 448 patients from 19 countries - the largest trial to date among patients with malignant pleural mesothelioma. Results showed overall survival was increased 30 percent (12.1 months for Alimta/cisplatin versus 9.3 months for cisplatin alone), and that 50.3 percent of patients treated with Alimta/cisplatin were alive a year later compared to 38.0 percent treated with cisplatin alone(1). Both the median and one-year rates of survival were statistically significant.

"For the first time ever we have proof that a chemotherapeutic regimen helps patients with malignant pleural mesothelioma live longer -- that's a big deal," said Claude Denham, M.D. a study co-investigator for US Oncology and a medical oncologist with Texas Oncology in Dallas. In addition, according to research findings, there was an improvement in lung function (forced vital capacity) on the Alimta/cisplatin arm compared to the cisplatin (or control) arm.(2)

Important Safety Information

The hematologic and non-hematologic side effects associated with Alimta are neutropenia, thrombocytopenia, anemia, nausea, vomiting, fatigue, diarrhea, skin rash and pain. To reduce the severity of treatment-related toxicities, all patients on Alimta must receive daily doses of folic acid and intramuscular injections of vitamin B12.

As with many chemotherapies, the dose-limiting toxicity of Alimta is usually myelosuppression. Specific dose-modification may be required for patients who experience grade 3 or 4 toxicities. Patients with kidney impairment should not receive Alimta therapy. Patients should also inform their doctors if they are taking NSAIDs like ibuprofen. It is recommended that frequent blood tests be performed on all patients receiving Alimta.

Additional Regulatory Milestones

In Europe, Lilly has completed its submissions for the use of Alimta, with cisplatin in the treatment of malignant pleural mesothelioma and single-agent Alimta in the second-line treatment of non-small cell lung cancer. Lilly has also recently submitted a New Drug Application to the FDA for the use of single-agent Alimta in the treatment of second-line non-small cell lung cancer.

For full prescribing information, visit http://www.Alimta.com .

Alimta® (pemetrexed, Lilly)

References:

(1) Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21:2636-2644, 2003

(2) Pistolesi M, Symanowski J, Gatzemeier U, et al. Improving pulmonary function in patients with malignant pleural mesothelioma: results from the phase III trial of pemetrexed + cisplatin vs. cisplatin. Lung Cancer 41:(Suppl 2) S220 (abstr P-513)


SOURCE: Eli Lilly and Company

ALIMTA [ (pemetrexed) is now available on expanded access basis. ALIMTA will be available on an expanded access use for people with malignant pleural mesothelioma, a cancer usually associated with exposure to asbestos. As of July 9, 2002 the Food and Drug Administration agreed to place ALIMTA in an expanded access program, which gives patients access to an agent that isn't yet commercially available, although the sponsor is actively pursuing marketing approval. Eli Lilly is pursuing approval of ALIMTA in combination with cisplatin for the treatment of malignant pleural mesothelioma, a disease that causes tumors to grow in the linings of the lung, or pleura. Patients live an average of six to nine months following diagnosis. The company said results of a Phase III trial showed that patients treated with ALIMTA and cisplatin combined lived longer and had less pain and shortness of breath, than patients treated with cisplatin alone. In the trial, the most common side effect from cisplatin and ALIMTA was a decrease in infection- fighting white blood cells. Under the expanded access program, ALIMTA will be given free of charge to patients who meet medical eligibility requirements.

Eli Lilly and Company: Alimta vs. Taxotere -- Similar Survival, Fewer Side Effects In Recurrent Non-Small Cell Lung Cancer

Business Editors/Health/Medical Writers

CHICAGO--(BUSINESS WIRE)--June 1, 2003--In a head-to-head trial comparing Alimta(R) (pemetrexed) to Taxotere(R) (docetaxel), Alimta showed a similar survival benefit with significantly fewer side effects in patients with recurrent non-small cell lung cancer (NSCLC). Results of this Phase III trial -- the largest Phase III trial ever conducted in second-line NSCLC -- were presented today at the 39th annual meeting of the American Society of Clinical Oncology, which is being held in Chicago.
"Before Taxotere, we had no agent that was proven to prolong life for patients with recurrent non-small cell lung cancer," said Nasser Hanna, M.D., who presented the findings and is an assistant professor of medicine at Indiana University Cancer Center. "Now, with these data on Alimta, we have observed a survival advantage, just as we have with Taxotere, but with fewer side effects."
Today's announcement was based on a global study of 571 patients with NSCLC previously treated with chemotherapy. Of these patients, 283 were randomized to receive Taxotere (75 mg/m2 on day one of a 21-day cycle; one-hour infusion). The remaining 288 patients received Alimta (500 mg/m2 on day one of a 21-day cycle; 10-minute infusion) supplemented with vitamin B12 and folic acid. Unlike Alimta, which is an investigational agent, Taxotere is approved for use in the treatment of first- and second-line NSCLC in both the U.S. and Europe.

According to the results:

-- Median survival, the study's primary endpoint, was similar between the two study arms. Those receiving Alimta had a median survival of 8.3 months, which means that half of the patients survived longer than 8.3 months and half shorter. The median survival for those who received Taxotere in this study was 7.9 months.
-- The incidence of severe neutropenia, a decrease in the number of white blood cells that increases the risk of infection, was 5 percent in the Alimta arm and 40 percent in the Taxotere arm, a difference that was statistically significant (p= less than 0.001).
-- The difference in the incidence of neutropenic fever and subsequent hospitalizations between the Alimta and Taxotere arms was also statistically significant: 2 percent for the Alimta patients compared to 13 percent for the Taxotere patients (p= less than 0.001).
-- In a third finding that reached statistical significance, the incidence of drug-related serious adverse events -- which include side effects that could lead to a life-threatening outcome, death or hospitalization -- was 10 percent for Alimta patients and 24 percent for Taxotere patients (p= less than 0.001).
-- The incidence of grades 3/4 Alanine Transaminase (Alanine Transaminase, or ALT, is a laboratory measurement of liver function) was 1.9 percent in the Alimta arm, a rate that was significantly greater than in the Taxotere arm (p=0.028). According to the findings, the incidence of grades 3/4 ALT in the Alimta arm was transient.

"Patients with cancer who are being treated in the second-line setting must heavily consider the risk-benefit ratio of another course of chemotherapy. It can be a difficult balancing act, but in this study, patients who received Alimta retained the chance of a benefit, but with fewer side effects, and that is important," said Paolo Paoletti, M.D., vice president of oncology products at Eli Lilly and Company. He added that Lilly is also evaluating the activity of Alimta in the first-line treatment of NSCLC.

Alimta in First-Line NSCLC

At this year's ASCO meeting, the following abstracts are being presented involving the use of Alimta in the first-line treatment of advanced NSCLC:

-- Alimta plus carboplatin in patients with advanced non-small
cell lung cancer: A phase II trial (Abstract #2580)

-- Phase II randomized study of pemetrexed + carboplatin or
oxaliplatin, as front-line chemotherapy in patients with
locally advanced or metastatic non-small cell lung cancer
(Abstract #2513)

"Alimta has already shown promising activity when combined with cisplatin in malignant pleural mesothelioma, a difficult-to-treat cancer in the lining of the lungs, and today's data support use with platinum compounds for non-small cell lung cancer," said Christian Manegold, professor of medicine at the University of Heidelberg, and consultant for medical oncology at the Thoracic Hospital in Heidelberg, Germany. "These findings are especially meaningful in Europe where platinum regimens provide feasible alternatives so patients may receive treatment on an outpatient basis. With their ease of use, Alimta combinations could provide attractive and convenient choices for these patients suffering from non-small cell lung cancer."

Lung cancer drug Alimta has fewer side effects

By Tim Friend, USA TODAY
CHICAGO — A new type of chemotherapy for patients with advanced lung cancer can dramatically enhance quality of life and reduce debilitating side effects, compared to one of the most commonly used current treatments, scientists reported Monday.
Experts said that Alimta, a new drug made by Eli Lilly, could potentially benefit tens of thousands of patients. Alimta is not yet commercially available.

More than 175,000 patients are diagnosed each year in the USA with lung cancer. Of those, 85% have non-small cell lung cancer. The disease in about two-thirds of patients with this kind of cancer has spread beyond the lungs at the time of diagnosis. The recommended treatment is chemotherapy, which extends median survival from about four months with no treatment to about eight months.

The study, presented at a meeting of the American Society of Clinical Oncology, compared Alimta with Taxotere in a group of 571 patients at medical centers in the USA, Canada, Spain, Brazil and Italy. Nasser Hanna of Indiana University in Indianapolis reported that the side effects were considerably fewer with Alimta.

Survival benefits were about equal, with Alimta patients living a median of 8.3 months compared with 7.9 months in patients on Taxotere.

For patients with only months to live after their diagnosis, quality of life becomes a critical issue.

For patients who are diagnosed with non-small cell lung cancer at earlier stages, the recommended treatment has been removal of the section of lung containing the tumor. Whether these patients live longer or better when given chemotherapy after surgery has been controversial.

But a large international study led by Thierry Le Chevalier of the Gustave Roussy Institute in Villejuif, France, suggests chemotherapy may be beneficial. The study of 1,867 patients from 33 countries found that patients who received surgery plus chemotherapy had about a 5% survival benefit over a period of five years.

Worldwide, 1.2 million people are diagnosed with lung cancer each year. About one-third are treated with surgery and may benefit from adding chemotherapy to their treatment, Le Chevalier said. The benefit may seem small, but it translates into the prevention of 7,000 deaths per year worldwide.

Another study, conducted by Roy Patchell of the University of Kentucky in Lexington, found that patients whose spinal cords have become compressed by tumors that have spread from other organs can gain significant relief from a new surgical procedure to remove the tumor.