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A Pathological Complete Response in Malignant Pleural Mesothelioma after Combination Chemotherapy with Carboplatin and Pemetrexed
CASE REPORT
A Pathological Complete Response in Malignant Pleural Mesothelioma after Combination Chemotherapy with Carboplatin and Pemetrexed Steven Chuan-Hao Kao, MBChB,* Brian McCaughan, FRACS,† Anita Muljono, FRCPA,‡ and Michael Boyer, MBBS, PhD*
(J Thorac Oncol. 2010;5: 405–406)
A
57-year-old nonsmoking male with previous asbestos exposure presented with a year history of right pleural effusion and 2-month history of night sweats and increasing chest pain. A mini thoracotomy, biopsy, and pleurodesis were performed. Intraoperatively, 1 liter of viscous yellow fluid was aspirated, and widespread dense infiltration of the parietal pleura was noted. The pleural biopsy confirmed malignant pleural mesothelioma (MPM) of epithelioid subtype (Figures 1A, B). His disease was staged with a computed tomography scan, which demonstrated disease in the right hemithorax only. He underwent six cycles of chemotherapy consisting of pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) every 3 weeks. Carboplatin was used due to preexisting hearing impairment. He tolerated it well with grade II anemia and grade I fatigue and nausea. A restaging computed tomography scan demonstrated a reduction of pleural thickness indicative of a radiologic partial response. Given the good response to chemotherapy with no extrathoracic disease, an extrapleural pneumonectomy (EPP) was performed 4 weeks postchemotherapy. He had no significant postoperative complications. A thorough examination of the pathologic specimens consisting of the right lung, pleura, hilar and mediastinal nodes, and port site demonstrated no residual malignancy. No adjuvant radiotherapy was given. He remains well without any evidence of recurrence 1 year postsurgery.
*Department of Medical Oncology, Sydney Cancer Centre; †Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital; and ‡Douglass Hanly Moir Pathology, Sydney, Australia. Disclosure: The authors declare no conflicts of interest. Address for correspondence: Michael Boyer, MBBS, PhD, Department of Medical Oncology, Gloucester House Level 6, Missenden Road, Camperdown, NSW 2050, Australia. E-mail: [email protected] Copyright © 2010 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/10/0503-0405
FIGURE 1. A, Malignant mesothelioma infiltrating the pleura and subpleural adipose tissue (at ⫻40). B, Mesothelial cells positive for calretinin stain (at ⫻200).
DISCUSSION Treatment with cisplatin/pemetrexed in MPM has resulted in a 3-month survival benefit and improvement in quality of life.1 Although the objective radiologic response rate is about 40%, the majority of responses are partial rather
Journal of Thoracic Oncology • Volume 5, Number 3, March 2010
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Kao et al.
Journal of Thoracic Oncology • Volume 5, Number 3, March 2010
than complete. A search in the literature yielded no radiologic complete response (CR) in the cisplatin/pemetrexed combination1 but up to 4% achieving radiologic CR with carboplatin/pemetrexed in a phase II trial.2 Nevertheless, the CRs were not confirmed pathologically. The treatment protocol of induction chemotherapy followed by EPP allows us to examine the pathologic response after chemotherapy. None of the studies confirmed a pathologic CR after three to four cycles of chemotherapy with cisplatin/gemcitabine3 or carboplatin/gemcitabine.4 Krug et al.5 recently reported their phase II trial using cisplatin/pemetrexed followed by EEP and radiotherapy. Three pathologic CRs were reported, which represented 5% of patients undergoing EPP. Despite the often difficult pathologic diagnosis of mesothelioma, we believe that our patient had MPM, given the two independent pathologic reviews of the initial biopsy confirming the invasive nature of the tumor and immunohistochemical evidence of mesothelial origin, as well as the supportive clinical picture of increasing pulmonary symptoms, and the typical radiologic changes. Furthermore, the radiologic response seen after chemotherapy lends further support to a malignant process rather than a benign one.
406
Therefore, we believe that this is the first reported case of a pathologic CR in a patient with MPM after carboplatin/ pemetrexed. In patients whom cisplatin is contraindicated, carboplatin seems to be a reasonable alternative in combination with pemetrexed. REFERENCES 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;21:2636 –2644. 2. 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;19:370 –373. 3. Flores RM, Krug LM, Rosenzweig KE, et al. Induction chemotherapy, extrapleural pneumonectomy, and postoperative high-dose radiotherapy for locally advanced malignant pleural mesothelioma: a phase II trial. J Thorac Oncol 2006;1:289 –295. 4. Rea F, Marulli G, Bortolotti L, et al. Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): feasibility and results. Lung Cancer 2007;57:89 –95. 5. 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;27:3007–3013.
Copyright © 2010 by the International Association for the Study of Lung Cancer
A Pathological Complete Response in Malignant Pleural Mesothelioma after Combination Chemotherapy with Carboplatin and Pemetrexed Steven Chuan-Hao Kao, MBChB,* Brian McCaughan, FRACS,† Anita Muljono, FRCPA,‡ and Michael Boyer, MBBS, PhD*
(J Thorac Oncol. 2010;5: 405–406)
A
57-year-old nonsmoking male with previous asbestos exposure presented with a year history of right pleural effusion and 2-month history of night sweats and increasing chest pain. A mini thoracotomy, biopsy, and pleurodesis were performed. Intraoperatively, 1 liter of viscous yellow fluid was aspirated, and widespread dense infiltration of the parietal pleura was noted. The pleural biopsy confirmed malignant pleural mesothelioma (MPM) of epithelioid subtype (Figures 1A, B). His disease was staged with a computed tomography scan, which demonstrated disease in the right hemithorax only. He underwent six cycles of chemotherapy consisting of pemetrexed (500 mg/m2) and carboplatin (area under the curve 5) every 3 weeks. Carboplatin was used due to preexisting hearing impairment. He tolerated it well with grade II anemia and grade I fatigue and nausea. A restaging computed tomography scan demonstrated a reduction of pleural thickness indicative of a radiologic partial response. Given the good response to chemotherapy with no extrathoracic disease, an extrapleural pneumonectomy (EPP) was performed 4 weeks postchemotherapy. He had no significant postoperative complications. A thorough examination of the pathologic specimens consisting of the right lung, pleura, hilar and mediastinal nodes, and port site demonstrated no residual malignancy. No adjuvant radiotherapy was given. He remains well without any evidence of recurrence 1 year postsurgery.
*Department of Medical Oncology, Sydney Cancer Centre; †Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital; and ‡Douglass Hanly Moir Pathology, Sydney, Australia. Disclosure: The authors declare no conflicts of interest. Address for correspondence: Michael Boyer, MBBS, PhD, Department of Medical Oncology, Gloucester House Level 6, Missenden Road, Camperdown, NSW 2050, Australia. E-mail: [email protected] Copyright © 2010 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/10/0503-0405
FIGURE 1. A, Malignant mesothelioma infiltrating the pleura and subpleural adipose tissue (at ⫻40). B, Mesothelial cells positive for calretinin stain (at ⫻200).
DISCUSSION Treatment with cisplatin/pemetrexed in MPM has resulted in a 3-month survival benefit and improvement in quality of life.1 Although the objective radiologic response rate is about 40%, the majority of responses are partial rather
Journal of Thoracic Oncology • Volume 5, Number 3, March 2010
405
Kao et al.
Journal of Thoracic Oncology • Volume 5, Number 3, March 2010
than complete. A search in the literature yielded no radiologic complete response (CR) in the cisplatin/pemetrexed combination1 but up to 4% achieving radiologic CR with carboplatin/pemetrexed in a phase II trial.2 Nevertheless, the CRs were not confirmed pathologically. The treatment protocol of induction chemotherapy followed by EPP allows us to examine the pathologic response after chemotherapy. None of the studies confirmed a pathologic CR after three to four cycles of chemotherapy with cisplatin/gemcitabine3 or carboplatin/gemcitabine.4 Krug et al.5 recently reported their phase II trial using cisplatin/pemetrexed followed by EEP and radiotherapy. Three pathologic CRs were reported, which represented 5% of patients undergoing EPP. Despite the often difficult pathologic diagnosis of mesothelioma, we believe that our patient had MPM, given the two independent pathologic reviews of the initial biopsy confirming the invasive nature of the tumor and immunohistochemical evidence of mesothelial origin, as well as the supportive clinical picture of increasing pulmonary symptoms, and the typical radiologic changes. Furthermore, the radiologic response seen after chemotherapy lends further support to a malignant process rather than a benign one.
406
Therefore, we believe that this is the first reported case of a pathologic CR in a patient with MPM after carboplatin/ pemetrexed. In patients whom cisplatin is contraindicated, carboplatin seems to be a reasonable alternative in combination with pemetrexed. REFERENCES 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;21:2636 –2644. 2. 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;19:370 –373. 3. Flores RM, Krug LM, Rosenzweig KE, et al. Induction chemotherapy, extrapleural pneumonectomy, and postoperative high-dose radiotherapy for locally advanced malignant pleural mesothelioma: a phase II trial. J Thorac Oncol 2006;1:289 –295. 4. Rea F, Marulli G, Bortolotti L, et al. Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): feasibility and results. Lung Cancer 2007;57:89 –95. 5. 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;27:3007–3013.
Copyright © 2010 by the International Association for the Study of Lung Cancer