Systemic Treatment of Malignant Pleural Mesothelioma
Systemic Treatment of Malignant Pleural Mesothelioma
To date, the combination of cisplatin and pemetrexed is the only evidence-based systemic treatment that leads to clinically significant survival improvement and amelioration of quality of life for MPM patients. If the patient cannot tolerate cisplatin, owing to age or clinically relevant comorbid conditions, carboplatin may be a reasonable alternative to cisplatin. At present, predictive molecular markers have no role in routine practice. Results of ongoing trials investigating bevacizumab and cisplatin plus pemetrexed are eagerly awaited, and may hopefully improve the still dismal prognosis of these patients. Maintenance therapy with thalidomide and histone deacetylase inhibitors failed to show any advantage in extending tumor control. In a small feasibility study, maintenance pemetrexed showed delayed responses and prolonged disease control, with a randomized Phase II study versus observation currently ongoing to confirm these findings.
Second-line therapies are increasingly becoming an unmet clinical need, because of the lack of proven efficacy and the optimal regimen not yet being defined. In pemetrexed-naive patients, pemetrexed may be considered a standard second-line treatment. In those having failed pemetrexed-based first-line chemotherapy, vinorelbine remains a viable option for palliation. In selected patients with prolonged PFS after first-line pemetrexed-based chemotherapy, rechallenge with pemetrexed-containing regimens should also be considered. Many targeted agents have been tested so far, showing only limited activity both as a single agent and in combination with chemotherapy. Novel immunotherapeutic agents are being explored, also in combination with chemotherapy, and may result in further advances in MPM patient management. Whenever possible, patients should be encouraged to participate in the few currently recruiting clinical trials.
Conclusion
To date, the combination of cisplatin and pemetrexed is the only evidence-based systemic treatment that leads to clinically significant survival improvement and amelioration of quality of life for MPM patients. If the patient cannot tolerate cisplatin, owing to age or clinically relevant comorbid conditions, carboplatin may be a reasonable alternative to cisplatin. At present, predictive molecular markers have no role in routine practice. Results of ongoing trials investigating bevacizumab and cisplatin plus pemetrexed are eagerly awaited, and may hopefully improve the still dismal prognosis of these patients. Maintenance therapy with thalidomide and histone deacetylase inhibitors failed to show any advantage in extending tumor control. In a small feasibility study, maintenance pemetrexed showed delayed responses and prolonged disease control, with a randomized Phase II study versus observation currently ongoing to confirm these findings.
Second-line therapies are increasingly becoming an unmet clinical need, because of the lack of proven efficacy and the optimal regimen not yet being defined. In pemetrexed-naive patients, pemetrexed may be considered a standard second-line treatment. In those having failed pemetrexed-based first-line chemotherapy, vinorelbine remains a viable option for palliation. In selected patients with prolonged PFS after first-line pemetrexed-based chemotherapy, rechallenge with pemetrexed-containing regimens should also be considered. Many targeted agents have been tested so far, showing only limited activity both as a single agent and in combination with chemotherapy. Novel immunotherapeutic agents are being explored, also in combination with chemotherapy, and may result in further advances in MPM patient management. Whenever possible, patients should be encouraged to participate in the few currently recruiting clinical trials.
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