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.
[34]
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 B
12. 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 B
12
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.
[35]
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 Un
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