Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

Alessandra Bearz,Gianpiero Fasola,Eleonora Berto,Francesco Rosetti,Adolfo Favaretto,Gilda Rossoni,Vanesa Gregorc,Renato Talamini,Umberto Tirelli,Massimiliano Berretta,Sandra Santarossa,Antonio Santo,Vincenzo De Pangher

doi:10.1186/1756-0500-5-482

Abstract

BackgroundAlthough first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment.MethodsWe retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment.ResultsOverall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively.ConclusionsIn our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression.

Highlights

First-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment
No activity for second-line treatment has been clearly reported in patients affected by malignant pleural mesothelioma; pemetrexed alone or combined with platin has shown efficacy even in patients previously treated with other drugs than pemetrexed [12,13], and some activity has been demonstrated for vinorelbine [14]
The regimens administered as re-treatment were pemetrexed at a dose of 500 mg/m2 combined with a platinum compound every three weeks or pemetrexed single agent at a dose of 500 mg/m2 every three weeks, using standard vitamin supplementation and dexamethasone prophylaxis

Summary

Introduction

First-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. No activity for second-line treatment has been clearly reported in patients affected by malignant pleural mesothelioma; pemetrexed alone or combined with platin has shown efficacy even in patients previously treated with other drugs than pemetrexed [12,13], and some activity has been demonstrated for vinorelbine [14]. In absence of a standard second-line treatment for malignant mesothelioma, we hypothesized efficacy from retreatment with pemetrexed alone or in combination with platin, when time to progression (TTP), calculated from the end of first-line chemotherapy and radiologic evidence of progression, was greater or equal than 6 months, as suggested for other pathologies with few therapeutic options [15]. We performed a retrospective analysis of patients re-treated with pemetrexed-based therapy in second line, to assess our hypothesis

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Discussion

Conclusion