C/MESOTELIOMA

C.1 TRATAMIENTO MULTIMODAL:

Los pacientes con buen PS, enfermedad estadío I-III y sin contraindicación por sus comorbilidades, son candidatos a tratamiento multimodal (Cirugia +/-RT +/-Quimioterapia). Los pacientes con enfermedad ST IV, mal PS o con variedad sarcomatoide no son candidatos a cirugía y en ellos se valorará mejores cuidados de soporte +/- quimioterapia.

  1. Sugarbaker DJ, Flores RM, Jaklitsch MT, et al. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg. 1999 Jan;117(1):54-63
  2. Krug LM, Pass HI, Rusch VW, 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 Jun 20;27(18):3007-13.
  3. de Perrot M, Feld R, Cho BC, et al.Trimodality therapy with induction chemotherapy followed by extrapleural pneumonectomy and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Clin Oncol. 2009 Mar 20;27(9):1413-8.
  4. Weder W, Stahel RA, Bernhard J, et al. Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural pneumonectomy in malignant pleural mesothelioma. Ann Oncol. 2007 Jul;18(7):1196-202.
  5. Bölükbas S, Manegold C, Eberlein M, et al. Survival after trimodality therapy for malignant pleural mesothelioma: Radical Pleurectomy, chemotherapy with Cisplatin/Pemetrexed and radiotherapy. Lung Cancer. 2011 Jan;71(1):75-81.

    Un estudio retrospectivo no encontró beneficio en supervivencia entre pacientes tratados con neumonectomía extrapleural y aquellos sin ese tipo de cirugía:

  6. Hasani A, Alvarez JM, Wyatt JM, et al. Outcome for patients with malignant pleural mesothelioma referred for Trimodality therapy in Western Australia. J Thorac Oncol. 2009 Aug;4(8):1010-6.

C.2 CIRUGIA

La elección del tipo de cirugía, es controversial ya que no se dispone de datos provenientes de estudios con grupos adecuadamente aleatorizados y las recomendaciones se hacen en base a publicaciones provenientes de grupos de consenso, quienes han obtenido la información a partir de análisis retrospectivos, series individuales y de una revisión sistemática. La ausencia de estudios comparativos no permite concluir que la cirugía mejore la supervivencia cuando se le compara con quimioterapia.

C.2.1 NEUMONECTOMIA EXTRAPLEURAL:

  1. Gadgeel S, Pass H. Malignant mesothelioma. Commun Oncol 2006; 3:215-224.
  2. Zauderer MG, Krug LM. The evolution of multimodality therapy for malignant pleural mesothelioma. Curr Treat Options Oncol. 2011 Jun;12(2):163-72.
  3. Kaufman AJ, Flores RM. Surgical treatment of malignant pleural mesothelioma. Curr Treat Options Oncol. 2011 Jun;12(2):201-16.
  4. Yan TD, Cao CQ, Boyer M et al. Improving survival results after surgical management of malignant pleural mesothelioma: an Australian institution experience. Ann Thorac Cardiovasc Surg. 2011 Jun;17(3):243-9.

C.2.2 PLEURECTOMIA/DECORTICACIÓN:

  1. Sugarbaker DJ, Jaklitsch MT, Bueno R, et al. Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg. 2004 Jul;128(1):138-46.
  2. Zahid I, Sharif S, Routledge T, et al. Is pleurectomy and decortication superior to palliative care in the treatment of malignant pleural mesothelioma? Interact Cardiovasc Thorac Surg. 2011 May;12(5):812-7.
  3. Shahin Y, Wellham J, Jappie R, et al How successful is lung-preserving radical surgery in the mesothelioma and radical surgery-trial environment? A case-controlled analysis. Eur J Cardiothorac Surg. 2011 Mar;39(3):360-3.
  4. Yan TD, Boyer M, Tin MM, et al. Extrapleural pneumonectomy for malignant pleural mesothelioma: outcomes of treatment and prognostic factors.J Thorac Cardiovasc Surg. 2009 Sep;138(3):619-24.
  5. Flores RM, Pass HI, Seshan VE et al. Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical management of malignant pleural mesothelioma: results in 663 patients. J Thorac Cardiovasc Surg. 2008 Mar;135(3):620-6, 626.e1-3.

C.3 QUIMIOTERAPIA

La quimioterapia está indicada en pacientes con buen PS y no candidatos a cirugía o como parte del tratamiento multidisciplinar (neoadyuvante o adyuvante) o en pacientes con variedad sarcomatoide. Estos datos están recogidos en una revisión sistemática y guía práctica

  1. Ellis P, Davies AM, Evans WK, et al. The use of chemotherapy in patients with advanced malignant pleural mesothelioma: a systematic review and practice guideline.J Thorac Oncol. 2006 Jul;1(6):591-601.
  2. Kelly RJ, Sharon E, Hassan R. Chemotherapy and targeted therapies for unresectable malignant mesothelioma.Lung Cancer. 2011 Sep;73(3):256-63.
  3. Krug LM. An overview of chemotherapy for mesothelioma. Hematol Oncol Clin North Am. 2005 Dec;19(6):1117-36, vii.

C.3.1 QUIMIOTERAPIA DE PRIMERA LINEA

C.3.1.1 QUIMIOTERAPIA DE PRIMERA LINEA CON PLATINO

El esquema estándar es cisplatino/pemetrexed. Ha demostrado beneficio en la supervivencia y es la única pauta aceptada por la FDA. Una alternativa al cisplatino es el Carboplatino

  1. Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003 Jul 15;21(14):2636-44.
  2. Santoro A, O'Brien ME, Stahel RA, 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 Jul;3(7):756-63.
  3. Katirtzoglou N, Gkiozos I, Makrilia N, et al. Carboplatin plus pemetrexed as first-line treatment of patients with malignant pleural mesothelioma: a phase II study. Clin Lung Cancer. 2010 Jan;11(1):30-5.
  4. Ceresoli GL, Zucali PA, Favaretto AG, et al.Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma. J Clin Oncol. 2006 Mar 20;24(9):1443-8.
  5. Castagneto B, Botta M, Aitini E, et al. Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM).Ann Oncol. 2008 Feb;19(2):370-3.
  6. van Haarst JM, Baas P, Manegold Ch, et al. Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma. Br J Cancer. 2002 Feb 1;86(3):342-5.
  7. Nowak AK, Byrne MJ, Williamson R, et al. A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma. Br J Cancer. 2002 Aug 27;87(5):491-6.

C.3.1.2 PRIMERA LINEA SIN PLATINO (MONOTERAPIA)

Es una opción para pacientes con estado general sub-optimo o comorbilidades que contraindiquen el uso de los derivados del platino

  1. Muers MF, Stephens RJ, Fisher P, 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 May 17;371(9625):1685-94.
  2. Scagliotti GV, Shin DM, Kindler HL, 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 Apr 15;21(8):1556-61.
  3. Taylor P, Castagneto B, Dark G, et al. Single-agent pemetrexed for chemonaïve and pretreated patients with malignant pleural mesothelioma: results of an International Expanded Access Program. J Thorac Oncol. 2008 Jul;3(7):764-71.

C.3.2 QUIMIOTERAPIA DE SEGUNDA LINEA

Hay muy pocos datos en segunda línea. Un estudio fase III, un fase II y un análisis post estudio de un fase III señalan, respectivamente, que pemetrexed, gemcitabina y vinorelbina son opciones a tener en cuenta.

  1. Ceresoli GL, Zucali PA, Gianoncelli L, et al. Second-line treatment for malignant pleural mesothelioma. Cancer Treat Rev. 2010 Feb;36(1):24-32.
  2. Jassem J, Ramlau R, Santoro A, 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 Apr 1;26(10):1698-704.
  3. Manegold C, Symanowski J, Gatzemeier U, et al. Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma.Ann Oncol. 2005 Jun;16(6):923-7.
  4. Stebbing J, Powles T, McPherson K, et al. The efficacy and safety of weekly vinorelbine in relapsed malignant pleural mesothelioma. Lung Cancer. 2009 Jan;63(1):94-7.

C.4 RADIOTERAPIA

C.4.1 COMO PARTE DE UNA POLITERAPIA

No existe un consenso respecto al momento de su integración en una terapia multimodal aunque varios estudios fase II y series de casos han demostrado una disminución en la tasa de recidivas locales después de una manipulación quirúrgica.

  1. Yajnik S, Rosenzweig KE, Mychalczak B, et al. Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2003 Aug 1;56(5):1319-26.
  2. Rusch VW, Rosenzweig K, Venkatraman E, et al. A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg. 2001 Oct;122(4):788-95.
  3. Gupta V, Mychalczak B, Krug L, et al. Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2005 Nov 15;63(4):1045-52.
  4. Gupta V, Krug LM, Laser B, et al. Patterns of local and nodal failure in malignant pleural mesothelioma after extrapleural pneumonectomy and photon-electron radiotherapy. J Thorac Oncol. 2009 Jun;4(6):746-50.
  5. Boutin C, Rey F, Viallat JR. Prevention of malignant seeding after invasive diagnostic procedures in patients with pleural mesothelioma. A randomized trial of local radiotherapy. Chest. 1995 Sep;108(3):754-8.
  6. Davies HE, Musk AW, Lee YC, et al. Prophylactic radiotherapy for pleural puncture sites in mesothelioma: the controversy continues. Curr Opin Pulm Med. 2008 Jul;14(4):326-30.

C.4.2 RADIOTERAPIA DE INTENSIDAD MODULADA

Es una alternativa explorada, no carente de toxicidades importantes.

  1. Rice DC, Stevens CW, Correa AM, et al. Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma.Ann Thorac Surg. 2007 Nov;84(5):1685-92; discussion 1692-3.
  2. Rice DC, Smythe WR, Liao Z, et al. Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):350-7.
  3. Miles EF, Larrier NA, Kelsey CR, et al. Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience. Int J Radiat Oncol Biol Phys. 2008 Jul 15;71(4):1143-50.
  4. Allen AM, Czerminska M, Jänne PA, et al. Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys. 2006 Jul 1;65(3):640-5.

C.4.3 RADIOTERAPIA PALIATIVA

En monoterapia, solo tiene papel como terapia paliativa. No hay consenso respecto a la dosis óptima para este propósito.

  1. Baldini EH. Radiation therapy options for malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg. 2009 Summer;21(2):159-63.
  2. Waite K, Gilligan D. The role of radiotherapy in the treatment of malignant pleural mesothelioma. Clin Oncol (R Coll Radiol). 2007 Apr;19(3):182-7.