Alimta, new approved drug to treat 'asbestos' lung cancer (mesothelioma) and also non-small cell lung cancer, will be available in UK and Europe
Australian researchers says screening blood test is possible for earlier detection of mesothelioma
1st November 2004, updated August 12 2005. /PSA Rising/ A new drug to help treat patients diagnosed with a devastating form of cancer will be available in the UK within months, its makers said in November 2004.
Alimta® (pemetrexed) was set to be commercially available in the UK by the beginning of 2005 for people with mesothelioma. Malignant pleural mesothelioma is a rare type of cancer that affects the inside lining of the chest cavity. It is usually associated with asbestos exposure.
The drug, also known as pemetrexed, is the first licensed treatment for malignant pleural mesothelioma, in combination with cisplatin, makers Lilly UK said today.
The cancer has no known cure. Professor Hilary Calvert, of the Northern Institute of Cancer Research, at the University of Newcastle upon Tyne, told the London, UK Daily Mail: "This form of cancer is usually diagnosed at an advanced stage at which point treatment with radiation therapy or surgery is not an option. Most of the patients I see only have a life expectancy after diagnosis of only a matter of months."
Patients with mesothelioma - often caused by exposure to asbestos - often die within a few years of late diagnosis.
But in studies published in The Lancet and the journal Lung Cancer in 2003 and 2005, Australian researcher B. W. Robinson says tests for levels of a key protein can identify over 80% of cases at an early stage (see abstracts).
As reported by the BBC "Earlier detection would mean doctors could treat the patient using chemotherapy, radiotherapy or surgery."
Treatment breakthrough
"Until now there has been no licensed chemotherapy available and patients have been more likely to have treatment aimed to relieve the symptoms rather than to control the disease," Calvert said.
Alimta was licensed in the USA February 2004 by the American Food and Drug Administration, which said patients lived, on average, nine to 13 months following diagnosis. Patients given Alimta and cisplatin lived three months longer than those on cisplatin alone.
The trials of Alimta have also seen a shrinking in the size of the tumor, thereby improving patients' quality of life, a spokeswoman for Lilly added.
Results from the US trial of Alimta for advanced mesothelioma demonstrated an objective tumor response rate for Alimta plus cisplatin that was greater than the objective tumor response rate for cisplatin alone. Median overall survival for subjects treated with Alimta plus cisplatin were 12.1 months compared with 9.3 months with cisplatin alone. Subjects given supplements of folic acid and vitamin B12 showed a 13.3 months median survival rate with the combination treatment compared with 10.0 months with cisplatin alone.
The trial showed that side effects
associated with the use of Alimta
may include
- Hematological effects
- Fatigue
- Fever
- Infection
- Stomatitis
- Pharyngitis
- Rash
Europe Approves Alimta for Non-small cell lung cancer
Lilly announced September 23 that Alimta® (pemetrexed) has been granted marketing authorization by the European Commission (EC) for two distinct cancer indications. Firstly, Alimta was approved in combination with cisplatin, a common chemotherapy agent, for the treatment of malignant pleural mesothelioma (MPM) in patients who have not received prior chemotherapy and are not candidates for surgery.
In addition, the Europeans approved Alimta as a single agent therapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after previous chemotherapy. Alimta is taken by means of a 10-minute infusion, once every three weeks.
Clinical research of Alimta is ongoing in first-line non-small cell lung cancer, and in small cell lung, breast, colon, ovarian and gastric cancers and in combination with radiation.
According to the 2003 World Health Organization Cancer Report, lung cancer is the world's most common cancer and the leading cause of cancer death for both men and women. There will be 1.2 million cases diagnosed this year around the world. The number of patients receiving treatment beyond the first-line in non-small cell lung cancer is steadily increasing and new therapy options are desperately needed in this setting.
Alimta was studied in a Phase III global clinical trial, the largest ever reported in second-line NSCLC, involving 571 randomized patients whose non-small cell lung cancer advanced beyond the first chemotherapy regimen. Among the patients enrolled in this study, 288 received docetaxel (75 mg/m2 on day one of a 21-day cycle; one-hour infusion) and 283 received Alimta (500 mg/m2 on day one of a 21-day cycle; 10-minute infusion; supplemented with vitamin B12 and folic acid). The primary endpoint was overall survival and secondary endpoints included toxicity, response rate, and progression-free survival.
In this study Alimta showed a survival rate comparable to that of docetaxel but with a more favorable side effect profile. Alimta caused significantly less neutropenia (an abnormal decrease in white blood cells) and hospitalization for neutropenia with fever, as well as less hair loss compared to docetaxel.
Patients on Alimta compared to therapy with docetaxel did show an increased transient elevation in Alanine Transaminase (ALT), a laboratory measurement of liver function. When Alimta is given as a single agent the most common side effects include disorders of the blood and lymphatic system, gastrointestinal disorders, fatigue, rash and desquamation (peeling of the skin).
In Europe, product launch and availability of Alimta will vary in each European Member State, Lilly says.
The drug was licensed in the UK earlier this year. More than 1,700 people in the UK are diagnosed with mesothelioma every year, decades after exposure to asbestos, and the numbers are set to peak at up to 2,500 in 2015.
Previously, those most at risk of exposure to asbestos were in industries such as shipbuilding, mining, and railway engineering. Areas of high incidence include London, Glasgow, Newcastle, Greater Manchester, Plymouth and Hampshire.
Earlier this year, the Government was warned deaths from asbestos-related diseases were reaching "epidemic" levels by a law firm which said it was dealing with hundreds of claims for people with mesothelioma.
Asbestos was banned in the UK in 1999, but has been used in a variety of products over the years, for
insulation, fireproofing and soundproofing
in various building materials and household appliances to vinyl flooring backing and to roofing materials and insulation.
Arizona State University Asbestos Management Program says; "In the 1970's, the U.S. began banning the use of asbestos in most building products due to studies confirming the harmful health effects caused by exposure to airborne asbestos. Manufacturers were allowed to deplete their existing stocks of asbestos materials, so some asbestos products were still being installed in buildings in the 1980's." Because a total ban has been stayed in US courts, some products containing asbestos still enter the USA.
Abstracts to research articles mentioned above.
Mesothelin-family proteins and diagnosis of mesothelioma.
Robinson BW , et al.
University Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Western Australia, Perth, Australia.
The Lancet , Volume 366 , Number 9483 , 30 July 2005
We assayed serum concentrations of soluble mesothelin-related proteins (SMR) using a double determinant (sandwich) ELISA in a blinded study of serum samples from 44 patients with histologically proven mesothelioma; 68 matched healthy controls, 40 of whom had been exposed to asbestos; and 160 patients with other inflammatory or malignant lung and pleural diseases. FINDINGS: 37 (84%) of 44 patients with mesothelioma had raised concentrations of SMR at a serum dilution of 1/80, compared with three (2%) of 160 patients with other cancers or other inflammatory lung or pleural diseases, and with none of 28 controls who had not been exposed to asbestos. SMR concentrations correlated with tumour size and increased during tumour progression. Seven of the 40 asbestos-exposed individuals had increased serum concentrations of SMR; three of those seven developed mesothelioma and one developed lung carcinoma within 1-5 years. None of the 33 asbestos-exposed participants whose serum samples had normal concentrations of SMR and who were followed up over 8 years developed mesothelioma. INTERPRETATION: Determination of SMR in serum could be a useful marker for diagnosis of mesothelioma and to monitor disease progression. It might also prove helpful for screening asbestos-exposed individuals for early evidence of mesothelioma. Back to main article
Malignant mesothelioma.
Robinson BW et al. Tumour Immunology Group, School of Medicine and Pharmacology, University of Western Australia, Australia.
Lancet. 2003 Nov 15;362(9396):1612-6.
Malignant mesothelioma is an aggressive, treatment-resistant tumour, which is increasing in frequency throughout the world. Although the main risk factor is asbestos exposure, a virus, simian virus 40 (SV40), could have a role. Mesothelioma has an unusual molecular pathology with loss of tumour suppressor genes being the predominant pattern of lesions, especially the P16INK4A, and P14ARF, and NF2 genes, rather than the more common p53 and Rb tumour suppressor genes. Cytopathology of mesothelioma effusions or fine-needle aspirations are often sufficient to establish a diagnosis, but histopathology is also often required. Patients typically present with breathlessness and chest pain with pleural effusions. Median survival is now 12 months from diagnosis. Palliative chemotherapy is beneficial for mesothelioma patients with high performance status. The role of aggressive surgery remains controversial and growth factor receptor blockade is still unproven. Gene therapy and immunotherapy are used on an experimental basis only. Patterns identified from microarray studies could be useful for diagnosis as well as prognostication. Back to main article
Soluble mesothelin-related protein--a blood test for mesothelioma.
Robinson BW, et al. University Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Perth, WA, Australia. In:
Lung Cancer. 2005 Jul;49 Suppl 1:S109-11.
Identification of tumor marker for mesothelioma (MM) might prove useful in diagnosis as well as for monitoring tumor in response to therapy and for screening at-risk individuals. We tested the hypothesis that soluble mesothelin-related protein (SMRP), a mesothelin family member, in the serum would be such a marker. Our data show that determination of SMRP in serum is a marker of MM with a sensitivity of sensitivity 83% and specificity 95% in the first 48 MM patients tested. Changes in serum SMRP levels parallel clinical course/tumor size and SMRP is elevated in 75% of patients at diagnosis. SMRP should also be useful for monitoring disease progression, and importantly, may prove useful for screening asbestos-exposed individuals for early MM. Back to main article
Researched, edited and written by J. Strax, Nov 1 2004. Updated Aug 12, 2005
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