Active anti-cancer treatment
Combination chemotherapy
Combination treatment usually produces higher response rates than single drug therapy.
There are few direct randomised comparisons of single versus combination drugs. One
three-armed study, which compared the efficacy of combined chemotherapy with a single
agent and a placebo in malignant mesothelioma, did not show significant differences in
survival between the combined chemotherapy and supportive care arms, although a trend
in favour of the single-agent arm (vinorelbine) was observed (201). It was prematurely
stopped because of low recruitment and required both chemotherapy arms to be
combined for analysis. This study has been criticised mainly because the combination
chemotherapy (Mitomycin C, Vinblastine, Cisplatin)(MVP) is considered inadequate and
the final study had insufficient power to address the effect of vinorelbine alone.
Two randomised studies have shown that combination chemotherapy that includes
cisplatin and pemetrexed or raltitrexed is associated with increased survival (195,
202). The median overall survival of patients given cisplatin–pemetrexed (12.1 months)
or cisplatin–raltitrexed (11.4 months) was significantly longer than that of patients
receiving cisplatin alone (9.3 and 8.8 months respectively), providing direct evidence
that combination treatment has a beneficial effect. A large compassionate-use study
of cisplatin or carboplatin in combination with pemetrexed suggests indirectly that
carboplatin and cisplatin have similar efficacy (203).
Therefore, pemetrexed in combination with a platinum agent (cisplatin or carboplatin) is
currently regarded as the optimal chemotherapy treatment for patients with malignant
mesothelioma (204). Raltitrexed is an active alternative; however, this drug is neither
approved nor reimbursed for this indication in Australia
Recommendation Grade
Combination chemotherapy (pemetrexed and cisplatin or carboplatin) rather
than single drug treatment should be used as first-line systemic treatment for
malignant pleural mesothelioma.