Improved survival after introduction of chemotherapy for malignant pleural mesothelioma in Slovenia: Population-based survey of 444 patients : Radiology and Oncology Jump to ContentJump to Main Navigation
Show Summary Details

Radiology and Oncology

The Journal of Association of Radiology and Oncology


IMPACT FACTOR 2015: 1.736

SCImago Journal Rank (SJR) 2015: 0.631
Source Normalized Impact per Paper (SNIP) 2015: 0.968
Impact per Publication (IPP) 2015: 1.796

Open Access
Online
ISSN
1581-3207
See all formats and pricing

 


Select Volume and Issue
Loading journal volume and issue information...

Improved survival after introduction of chemotherapy for malignant pleural mesothelioma in Slovenia: Population-based survey of 444 patients

Viljem Kovac1 / Matjaz Zwitter1 / Tina Zagar1

Department of Radiotherapy, Institute of Oncology, Ljubljana, Slovenia1

Cancer Registry of Republic of Slovenia, Institute of Oncology, Ljubljana, Slovenia2

This content is open access.

Citation Information: Radiology and Oncology. Volume 46, Issue 2, Pages 136–144, ISSN (Online) 1581-3207, ISSN (Print) 1318-2099, DOI: 10.2478/v10019-012-0032-0, May 2012

Publication History

Published Online:
2012-05-30

Improved survival after introduction of chemotherapy for malignant pleural mesothelioma in Slovenia: Population-based survey of 444 patients

Background. Malignant pleural mesothelioma is a rare tumour with increasing frequency throughout the world. Due to long latency after exposure to asbestos, restrictions in the production and use of asbestos have not yet alleviated the burden of mesothelioma. During the last decade, several trials confirmed the benefit of systemic treatment with drugs such as doublets with cisplatina and gemcitabine or pemetrexed for carefully selected patients in good performance status. The purpose of this survey was to assess the impact of systemic treatment for the whole national population of patients with mesothelioma.

Patients and methods. A retrospective study included all patients in Slovenia with histologically confirmed diagnosis of malignant pleural mesothelioma in the period from 1974 till 2008. Data from the Cancer Registry of Slovenia were supplemented by review of clinical records of the Institute of Oncology in Ljubljana where virtually all non-surgical treatment for mesothelioma was performed. We analysed the incidence, treatment, and survival of patients treated in the era of infrequent chemotherapy (1974-2003, the first period) and after it (2004-2008, the second period).

Results. The survey included 444 patients, of whom 325 and 119 were diagnosed in the first and second period, respectively. Joinpoint regression analysis showed that after 1995 the trend in crude incidence rates increased more rapidly; the annual change was 0.03 per 100,000 per year before 1995 and 0.06 per 100,000 per year after. There was clear male predominance (70%) throughout the period covered by the survey. The proportion of patients above 65 years of age increased from 41.8% to 54.6% for the first and second period, respectively (p = 0.02). With a total of 52 (11.7%) operated patients, surgical treatment was rare and used only for selected patients with early disease and without comorbidity, leading to their relatively long median survival of 13.6 months. Chemotherapy was applied to 56 (17.2%) and to 96 (80.7%) patients during the first and second period, respectively. While a variety of older drugs were used in the first period, the most common regimen in the second period (applied to 91 patients) was doublet of low-dose gemcitabine in prolonged infusion and cisplatin. For the whole population of patients regardless the mode of treatment, median survival was 7.4 and 12.6 months (p-value = 0.037) for the first and second period, respectively.

Conclusions. Increasing incidence, male predominance and increased proportion of older patients confirm that the burden of mesothelioma persists in spite of a 15-years old ban in the production of asbestos. Modern chemotherapy, and in particular treatment with low-dose gemcitabine in prolonged infusion and cisplatin significantly prolonged median survival of patients with malignant pleural mesothelioma in Slovenia.

Keywords: malignant pleural mesothelioma; incidence; survival; chemotherapy; gemcitabine in prolonged infusion

  • Robinson BW, Lake RA. Advances in malignant mesothelioma. N Engl J Med 2005; 353: 1591-603. [PubMed] [CrossRef]

  • Franko A, Dolzan V, Kovac V, Arneric N, Dodic-Fikfak M. Soluble mesothelinrelated peptides levels in patients with malignant mesothelioma. Dis Markers 2012; 32: 123-31. [CrossRef]

  • Robinson BWS, Musk AW, Lake RA. Malignant mesothelioma. Lancet 2005; 366: 397-408. [CrossRef] [PubMed]

  • Hodgson JT, McElvenny DM, Darnton AJ, Price MJ, Peto J. The expected burden of mesothelioma mortality in Great Britain from 2002 to 2050. Br J Cancer 2005; 92: 587-93.

  • Marinaccio A, Binazzi A, Cauzillo G, Cavone D, Zotti RD, Ferrante P, et al; Italian Mesothelioma Register (ReNaM) Working Group. Analysis of latency time and its determinants in asbestos related malignant mesothelioma cases of the Italian register. Eur J Cancer 2007; 43: 2722-8. [CrossRef]

  • Rake C, Gilham C, Hatch J, Darnton A, Hodgson J, Peto J. Occupational, domestic and environmental mesothelioma risks in the British population: a case-control study. Br J Cancer 2009; 100: 1175-83. [PubMed] [CrossRef]

  • Milano MT, Zhang H. Malignant pleural mesothelioma. A population-based study of survival. J Thorac Oncol 2010; 5: 1841-8. [PubMed] [CrossRef]

  • Podobnik J, Kocijancic I, Kovac V, Sersa I. 3T MRI in evaluation of asbestosrelated thoracic diseases - preliminary results. Radiol Oncol 2010; 44: 92-6.

  • Gill RR. Imaging of mesothelioma. Recent Results Cancer Res 2011; 189: 27-43.

  • Peake MD, Entwisle J, Gray SG. Malignant pleural mesothelioma: clinical presentation, radiological evaluation and diagnosis. In: O'Byrne K, Rusch V, editors. Malignant pleural mesothelioma. Oxford: Oxford University Press; 2006. p. 35-60.

  • Zauderer MG, Krug LM. The evolution of multimodality therapy for malignant pleural mesothelioma. Curr Treat Options Oncol 2011; 12: 163-72.

  • Okada M, Mimura T, Ohbayashi C, Sakuma T, Soejima T, Tsubota N. Radical surgery for malignant pleural mesothelioma: results and prognosis. Interact Cardiovasc Thorac Surg 2008; 7: 102-6.

  • Scherpereel A, Astoul P, Baas P, Berghmans T, Clayson H, de Vuyst P, et al; European Respiratory Society/European Society of Thoracic Surgeons Task Force. Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J 2010; 35: 479-95. [CrossRef]

  • Eržen J, Vidmar S, Sok M, Debeljak A, Kecelj P, Kovač V, et al. Surgical treatment of malignant pleural mesothelioma. Experience in Slovenia in the interdisciplinary approach. Radiol Oncol 2005; 39: 123-31.

  • Krug LM, Pass HI, Rusch VW, Kindler HL, Sugarbaker DJ, Rosenzweig KE, et al. Multicenter phase II trial of neoadjuvant pemetrexed plus cisplatin followed by extrapleural pneumonectomy and radiation for malignant pleural mesothelioma. J Clin Oncol 2009; 27: 3007-13. [PubMed] [CrossRef]

  • Muers MF, Stephens RJ, Fisher P, Darlison L, Higgs CM, Lowry E, et al. Active symptom control with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma (MS01): a multicentre randomised trial. Lancet 2008; 371: 1685-94.

  • Zwitter M. Dutch statistics on lung cancer: sobering experience for a new approach. J Thorac Oncol 2012; 7: 269-71. [PubMed] [CrossRef]

  • Kovac V, Zwitter M, Rajer M, Marin A, Debeljak A, Smrdel U, et al. A phase II trial of low-dose gemcitabine in prolonged infusion and cisplatin for malignant pleural mesothelioma. Anticancer Drugs 2012; 23: 230-8. [PubMed] [CrossRef]

  • Damhuis RA, Schroten C, Burgers JA. Population-based survival for malignant mesothelioma after introduction of novel chemotherapy. Eur Respir J 2011; Dec 1. [Epub ahead of print]

  • Debevec M, Kovač V, Debeljak A, Eržen J, Remškar Z, Kern I. [Malignant pleural mesothelioma. Analysis of patients in Slovenia 1980-1997]. [Slovenian]. Zdrav Vest 2000; 69: 599-606.

  • Debeljak A, Kecelj P, Kern I, Eržen J, Kovač V, Rott T. Medical thorascopy in pleural malignant mesothelioma. In: Zaltloukal P, Petruželka L, editors. Lung Cancer. Current Topics. Prague: Monduzzi Editore; 2001. p. 81-6.

  • Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med 2000; 19: 335-51. [CrossRef] [PubMed]

  • Hmeljak J, Coer A. Presence and role of Simian virus 40 (SV40) in malignant pleural mesothelioma. Radiol Oncol 2009; 43: 9-16.

  • Hmeljak J, Kern I, Cor A. No implication of Simian virus 40 in pathogenesis of malignant pleural mesothelioma in Slovenia. Tumori 2010; 96: 667-73. [PubMed]

  • Fennell DA, Gaudino G, O'Byrne KJ, Mutti L, van Meerbeeck J. Advances in the systemic therapy of malignant pleural mesothelioma. Nat Clin Pract Oncol 2008; 5: 136-47. [PubMed] [CrossRef]

  • Erculj N, Kovac V, Hmeljak J, Dolzan V. The influence of platinum pathway polymorphisms on the outcome in patients with malignan pleural mesothelioma. Ann Oncol 2012; 23: 961-7. [CrossRef]

  • Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010; 363: 733-42. [CrossRef] [PubMed]

  • Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, 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: 2629-30.

  • Lee CW, Murray N, Anderson H, Rao SC, Bishop W. Outcomes with first-line platinum-based combination chemotherapy for malignant pleural mesothelioma: A review of practice in British Columbia. Lung Cancer 2009; 64: 308-13. [PubMed] [CrossRef]

  • Byrne MJ, Davidson JA, Musk AW, Dewar J, van Hazel G, Buck M, et al. Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study. J Clin Oncol 1999; 17: 25-30. [PubMed]

  • Aversa SM, Favaretto AG. Carboplatin and gemcitabine chemotherapy for malignant pleural mesothelioma: a phase II study of the GSTPV. Clin Lung Cancer 1999; 1: 73-7. [CrossRef]

  • van Haarst JMW, Baas P, Manegold C, Schouwink JH, Burgers JA, de Bruin HG, et al. Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma. Br J Cancer 2002; 86: 342-5. [PubMed] [CrossRef]

  • Nowak AK, Byrne MJ, Williamson R, Ryan G, Segal A, Fielding D, Mitchell P, Musk AW, Robinson BW. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma. Br J Cancer 2002; 87: 491-6. [CrossRef] [PubMed]

  • Mikulski SM, Costanzi JJ, Vogelzang NJ, McCachren S, Taub RN, Chun H, et al. Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma. J Clin Oncol 2002; 20: 274-81. [CrossRef] [PubMed]

  • Favaretto AG, Aversa SM, Paccagnella A, Manzini Vde P, Palmisano V, Oniga F, et al. Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study. Cancer 2003; 97: 2791-7. [CrossRef]

  • Andreopoulou E, Ross PJ, O'Brien ME, Ford HE, Priest K, Eisen T, et al. The palliative benefits of MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in patients with malignant mesothelioma. Ann Oncol 2004; 15: 1406-12. [CrossRef] [PubMed]

  • van Meerbeeck JP, Gaafar R, Manegold C, van Klaveren RJ, van Marck EA, Vincent M, et al. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer, Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol 2005; 23: 6881-9. [PubMed]

  • Castagneto B, Zai S, Dongiovanni D, Muzio A, Bretti S, Numico G, et al. Cisplatin and gemcitabine in malignant pleural mesothelioma: a phase II study. Am J Clin Oncol 2005; 28: 223-6. [PubMed] [CrossRef]

  • Berghmans T, Lafitte JJ, Paesmans M, Stach B, Berchier MC, Wackenier P, et al. A phase II study evaluating the cisplatin and epirubicin combination in patients with unresectable malignant pleural mesothelioma. Lung Cancer 2005; 50: 75-82. [PubMed] [CrossRef]

  • Jänne PA, Simon GR, Langer CJ, Taub RN, Dowlati A, Fidias P, et al. Phase II trial of pemetrexed and gemcitabine in chemotherapy-naive malignant pleural mesothelioma. J Clin Oncol 2008; 26: 1465-71. [PubMed] [CrossRef]

  • Ceresoli GL, Zucali PA, Favaretto AG, Grossi F, Bidoli P, Del Conte G, et al. Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol 2006; 24: 1443-8. [CrossRef] [PubMed]

  • Obasaju CK, Ye Z, Wozniak AJ, Belani CP, Keohan ML, Ross HJ, et al; Pemetrexed Expanded Access Program Investigators. Single-arm, open label study of pemetrexed plus cisplatin in chemotherapy naïve patients with malignant pleural mesothelioma: outcomes of an expanded access program. Lung Cancer 2007; 55: 187-94. [PubMed] [CrossRef]

  • Santoro A, O'Brien ME, Stahel RA, Nackaerts K, Baas P, Karthaus M, et al. Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program. J Thorac Oncol 2008; 3: 756-63. [PubMed] [CrossRef]

  • Castagneto B, Botta M, Aitini E, Spigno F, Degiovanni D, Alabiso O, et al. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM). Ann Oncol 2008; 19: 370-3. [CrossRef] [PubMed]

  • Kalmadi SR, Rankin C, Kraut MJ, Jacobs AD, Petrylak DP, Adelstein DJ, et al. Gemcitabine and cisplatin in unresectable malignant mesothelioma of the pleura: a phase II study of the Southwest Oncology Group (SWOG 9810). Lung Cancer 2008; 60: 259-63.

  • Hillerdal G, Sorensen JB, Sundström S, Riska H, Vikström A, Hjerpe A. Treatment of malignant pleural mesothelioma with carboplatin, liposomized doxorubicin, and gemcitabine: a phase II study. J Thorac Oncol 2008; 3: 1325-31. [PubMed] [CrossRef]

  • Sørensen JB, Frank H, Palshof T. Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma. Br J Cancer 2008; 99: 44-50. [CrossRef] [PubMed]

  • Ralli M, Tourkantonis I, Makrilia N, Gkini E, Kotteas E, Gkiozos I, et al. Docetaxel plus gemcitabine as first-line treatment in malignant pleural mesothelioma: a single institution phase II study. Anticancer Res 2009; 29: 3441-4. [PubMed]

  • Sørensen JB, Bech C, Sorensen P, Frank H. Phase II study of carboplatin and vinorelbine 1st line treatment in advanced malignant pleural mesothelioma. [Abstract]. J Thorac Oncol 2011; 6(6 Suppl): S1354.-5.

  • Zwitter M, Kovac V, Smrdel U, Kocijancic I, Segedin B, Vrankar M. Phase I-II trial of low-dose gemcitabine in prolonged infusion and cisplatin for advanced non-small cell lung cancer. Anticancer Drugs 2005; 16: 1129-34. [CrossRef] [PubMed]

  • Zwitter M, Kovac V, Smrdel U, Vrankar M, Zadnik V. Gemcitabine in brief versus prolonged low-dose infusion, both combined with cisplatin, for advanced non-small cell lung cancer: a randomized phase II clinical trial. J Thorac Oncol 2009; 4: 1148-55. [PubMed] [CrossRef]

  • Zwitter M, Kovac V, Rajer M, Vrankar M, Smrdel U. Two schedules of chemotherapy for patients with non-small cell lung cancer in poor performance status: a phase II randomized trial. Anticancer Drugs 2010; 21: 662-8. [CrossRef] [PubMed]

  • Kovac V. Zwitter M. Cisplatin with Alimpta or gemcitabine in long infusion for mesothelioma (AGILI). Available: http://clinicaltrials.gov/ct2/show/NCT01281800

  • Brodowicz T, Krzakowski M, Zwitter M, Tzekova V, Ramlau R, Ghilezan N, et al; Central European Cooperative Oncology Group CECOG. Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer 2006; 52: 155-63. [PubMed] [CrossRef]

  • Velez M, Arango BA, Perez CA, Santos ES. Safety and efficacy of pemetrexed in maintenance therapy of non-small cell lung cancer. Clin Med Insights Oncol 2012; 6: 117-24. [PubMed] [CrossRef]

  • Ceresoli GL, Zucali PA, De Vincenzo F, Gianoncelli L, Simonelli M, Lorenzi E, et al. Retreatment with pemetrexed-based chemotherapy in patients with malignant pleural mesothelioma. Lung Cancer 2011; 72: 73-7. [CrossRef] [PubMed]

  • Zucali PA, Simonelli M, Michetti G, Tiseo M, Ceresoli GL, Collovà E, et al. Second-line chemotherapy in malignant pleural mesothelioma: Results of a retrospective multicenter survey. Lung Cancer 2012; 75: 360-7. [PubMed] [CrossRef]

  • Goricar K, Erculj N, Zadel M, Dolzan V. Genetic polymorphisms in homologous recombination repair genes in healthy Slovenian population and their influence on DNA damage. Radiol Oncol 2012; 46: 46-53. [PubMed]

  • Zimling ZG, Sørensen JB, Gerds TA, Bech C, Andersen CB, Santoni-Rugiu E. Low ERCC1 expression in malignant pleural mesotheliomas treated with cisplatin and vinorelbine predicts prolonged progression-free survival. J Thorac Oncol 2012; 7: 249-56.

  • Erculj N, Kovac V, Hmeljak J, Franko A, Dodič-Fikfak M, Dolzan V. The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma. Pharmacogenet Genomics 2012; 22: 58-68. [CrossRef] [PubMed]

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Viljem Kovac, Metoda Dodic-Fikfak, Niko Arneric, Vita Dolzan, and Alenka Franko
Radiology and Oncology, 2015, Volume 0, Number 0
[2]
R.A. Damhuis, A. Khakwani, H. De Schutter, A.L. Rich, J.A. Burgers, and J.P. van Meerbeeck
Lung Cancer, 2015
[3]
Katja Goričar, Viljem Kovač, and Vita Dolžan
Pharmacogenomics, 2014, Volume 15, Number 7, Page 941
[4]
S. Murphy, G. Probert, J. Anderson, S. Pollock, I. Taylor, H. Clague, and K. Sridharan
Clinical Oncology, 2013, Volume 25, Number 12, Page 713
[5]
Julija Hmeljak, Nina Erčulj, Vita Dolžan, Jože Pižem, Izidor Kern, Viljem Kovač, Maja Čemažar, and Andrej Cör
Virchows Archiv, 2013, Volume 462, Number 3, Page 315
[6]
Yaping Xu, Youhua Jiang, Xinmin Yu, Qixun Chen, Xinming Zhou, and Weimin Mao
Radiology and Oncology, 2013, Volume 47, Number 1

Comments (0)

Please log in or register to comment.