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Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma

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Abstract

There is no well-defined standard third-line chemotherapy for advanced malignant pleural mesothelioma (MPM). However, combination of carboplatin, liposomised doxorubicin (Caelyx) and gemcitabine (CCG regimen) has revealed noteworthy activity when used as first-line treatment. The aim of this study is to assess efficacy and toxicity profile for patients with MPM receiving CCG regimen as a third-line treatment. Carboplatin (AUC 5), Caelyx (30 mg/m2) and Gemcitabine (1,000 mg/m2) day 1, together with Gemcitabine (800 mg/m2) day 8, were given in up to six cycles. Patients were unresectable, PS 0–2, and had previously received a first-line platinum-based regimen and either vinorelbine or pemetrexed as second line. Response to treatment was assessed by CT scan using Modified RECIST criteria for mesothelioma. Forty-three patients were treated between 2010 and 2014. Median age was 67 years (47–82), 72 % males, and 79 % had previous asbestos exposure. Ninety per cent had PS 0–1, 58 % had epitheloid subtype and 63 % IMIG stage IV. First-line treatment was platinum and pemetrexed in 42 cases. Second-line treatment was vinorelbine in 42 cases and pemetrexed in one patient. Median lead time from cessation of second-line treatment to start of third CCG was 1 month. Twenty-eight per cent of the patients received six cycles, while treatment was postponed due to toxicities, mainly haematological, in 56 % of cases. No toxicity-related deaths occurred. Partial response (PR) occurred in 14 %, and disease control rate (DCR) was 60 %. Medians of overall survival (OS) from diagnosis and from start of CCG treatment were 25.2 months (18.4–31.5 months) and 6.8 months (5.4–8.4 months), respectively. Progression-free survival (PFS) was 4.1 months (1.7–4.5 months). Third-line CCG revealed a noteworthy efficacy with a DCR of 60.4 %. It was, however, associated with considerable haematological toxicity. Less toxic and more active treatment options are clearly needed.

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References

  1. Hillerdal G, et al. Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study. J Thorac Oncol. 2008;3(11):1325–31.

    Article  PubMed  Google Scholar 

  2. Ellis P, Davis A, Evans WK, Haynes AE, Lloyd NS. Lung cancer disease site group of cancer care ontario’s program in evidence-based care. The use of chemotherapy in patients with advanced malignant pleural mesothelioma: a systematic review and practice guideline. Evidence-based series 7-14-1 Version 2. 2012.

  3. Van Schil PE, et al. Multimodal management of malignant pleural mesothelioma: where are we today? Eur Respir J. 2014;44(3):754–64.

    Article  PubMed  Google Scholar 

  4. Papaspyros S, Papaspyros S. Surgical management of malignant pleural mesothelioma: impact of surgery on survival and quality of life-relation to chemotherapy, radiotherapy, and alternative therapies. ISRN Surg. 2014;2014:817203.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Soerensen JB. Current concepts in chemotherapy for malignant pleural mesothelioma. Clin Respir J. 2008;2(2):74–9.

    Article  Google Scholar 

  6. Ceresoli GL, et al. Therapeutic outcome according to histologic subtype in 121 patients with malignant pleural mesothelioma. Lung Cancer. 2001;34(2):279–87.

    Article  CAS  PubMed  Google Scholar 

  7. Tomek S, Manegold C. Chemotherapy for malignant pleural mesothelioma: past results and recent developments. Lung Cancer. 2004;45(Suppl 1):S103–19.

    Article  PubMed  Google Scholar 

  8. Scagliotti GV, et al. Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma. J Clin Oncol. 2003;21(8):1556–61.

    Article  CAS  PubMed  Google Scholar 

  9. Vogelzang NJ, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003;21(14):2636–44.

    Article  CAS  PubMed  Google Scholar 

  10. Ceresoli GL, et al. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006;24(9):1443–8.

    Article  CAS  PubMed  Google Scholar 

  11. Soerensen JB, Frank H, Palshof T. Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma. Br J Cancer. 2008;99(1):44–50.

    Article  Google Scholar 

  12. Van Haarst JM, et al. Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma. Br J Cancer. 2002;86(3):342–5.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Arrieta O, et al. A phase II trial of prolonged, continuous infusion of low-dose gemcitabine plus cisplatin in patients with advanced malignant pleural mesothelioma. Cancer Chemother Pharmacol. 2014;73(5):975–82.

    Article  CAS  PubMed  Google Scholar 

  14. Jassem J, et al. Phase III trial of pemetrexed plus best supportive care compared with best supportive care in previously treated patients with advanced malignant pleural mesothelioma. J Clin Oncol. 2008;26(10):1698–704.

    Article  CAS  PubMed  Google Scholar 

  15. Soerensen JB, et al. Pemetrexed as second-line treatment in malignant pleural mesothelioma after platinum-based first-line treatment. J Thorac Oncol. 2007;2(2):147–52.

    Google Scholar 

  16. Soerensen JB, S.P., Frank H. Carboplatin and vinorelbine first-line chemotherapy in Malignant Mesothelioma, Proceedings World Conference on Mesothelioma (IMIG), 2010. abstract 56.

  17. Stebbing J, et al. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer. 2009;63(1):94–7.

    Article  PubMed  Google Scholar 

  18. Soerensen JB, Urbanska E, Langer SW, Aamdal E. Second-line oral vinorelbine following 1st line platinum and pemetrexed in malignant pleural mesothelioma. Eur J Clin Med Oncol. 2012;4(4):6–13.

    Google Scholar 

  19. Toyokawa G, et al. Gemcitabine and vinorelbine as second-line or beyond treatment in patients with malignant pleural mesothelioma pretreated with platinum plus pemetrexed chemotherapy. Int J Clin Oncol. 2014;19(4):601–6.

    Article  CAS  PubMed  Google Scholar 

  20. Zauderer MG, et al. Vinorelbine and gemcitabine as second- or third-line therapy for malignant pleural mesothelioma. Lung Cancer. 2014;84(3):271–4.

    Article  PubMed  Google Scholar 

  21. Uziely B, et al. Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies. J Clin Oncol. 1995;13(7):1777–85.

    CAS  PubMed  Google Scholar 

  22. Hillerdal G, et al. Treatment of malignant pleural mesothelioma with liposomized doxorubicin: prolonged time to progression and good survival. A Nordic study. Clin Respir J. 2008;2(2):80–5.

    Article  CAS  PubMed  Google Scholar 

  23. Byrne MJ, et al. Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study. J Clin Oncol. 1999;17(1):25–30.

    CAS  PubMed  Google Scholar 

  24. Vogelzang NJ, et al. Carboplatin in malignant mesothelioma: a phase II study of the cancer and leukemia group B. Cancer Chemother Pharmacol. 1990;27(3):239–42.

    Article  CAS  PubMed  Google Scholar 

  25. Byrne MJ, Nowak AK. Modified RECIST criteria for assessment of response in malignant pleural mesothelioma. Ann Oncol. 2004;15(2):257–60.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Vinicius Araújo B. de Lima.

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On behalf of the Danish Mesothelioma Group.

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de Lima, V.A.B., Sørensen, J.B. Third-line chemotherapy with carboplatin, gemcitabine and liposomised doxorubicin for malignant pleural mesothelioma. Med Oncol 32, 11 (2015). https://doi.org/10.1007/s12032-014-0458-x

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