Chemotherapy:
Chemotherapy
is the only treatment for mesothelioma that has been proven to improve survival
in randomised and controlled trials. The landmark study published in 2003 by
Vogelzang and colleagues compared cisplatin chemotherapy alone with a
combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in
patients who had not received chemotherapy for malignant pleural mesothelioma
previously and were not candidates for more aggressive "curative"
surgery. This trial was the first to report a survival advantage from
chemotherapy in malignant pleural mesothelioma, showing a statistically
significant improvement in median survival from 10 months in the patients
treated with cisplatin alone to 13.3 months in the group of patients treated
with cisplatin in the combination with pemetrexed and who also received
supplementation with folate and vitamin B12. Vitamin supplementation was given
to most patients in the trial and pemetrexed related side effects were
significantly less in patients receiving pemetrexed when they also received
daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks
compared with patients receiving pemetrexed without vitamin supplementation.
The objective response rate increased from 20% in the cisplatin group to 46% in
the combination pemetrexed group. Some side effects such as nausea and
vomiting, stomatitis, and diarrhoea were more common in the combination
pemetrexed group but only affected a minority of patients and overall the
combination of pemetrexed and cisplatin was well tolerated when patients
received vitamin supplementation; both quality of life and lung function tests
improved in the combination pemetrexed group. In February 2004, the United
States Food and Drug Administration approved pemetrexed for treatment of
malignant pleural mesothelioma. However, there are still unanswered questions
about the optimal use of chemotherapy, including when to start treatment, and
the optimal number of cycles to give.
Cisplatin
in combination with raltitrexed has shown an improvement in survival similar to
that reported for pemetrexed in combination with cisplatin, but raltitrexed is
no longer commercially available for this indication. For patients unable to
tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine
is an alternative, or vinorelbine on its own, although a survival benefit has
not been shown for these drugs. For patients in whom cisplatin cannot be used,
carboplatin can be substituted but non-randomised data have shown lower
response rates and high rates of haematological toxicity for carboplatin-based
combinations, albeit with similar survival figures to patients receiving
cisplatin.
In January
2009, the United States FDA approved using conventional therapies such as
surgery in combination with radiation and or chemotherapy on stage I or II
Mesothelioma after research conducted by a nationwide study by Duke University
concluded an almost 50 point increase in remission rates.
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