Case Report Received: March 19, 2015 Accepted: June 23, 2015 Published online: August 13, 2015
Chemotherapy 2014;60:321–324 DOI: 10.1159/000437136
Intrapleural Trastuzumab Therapy for Malignant Pleural Effusion from HER2 Overexpression in Metastatic Gastric Cancer Elena Orlandi a Patrizia Mordenti a Adriano Zangrandi b Luigi Cavanna a
Departments of a Oncology-Hematology and b Pathology, Ospedale Guglielmo da Saliceto, Piacenza, Italy
Key Words Malignant pleural effusion · Trastuzumab · Gastric cancer · HER2 overexpression
Abstract Background: Malignant pleural effusion (MPE) is an extremely common problem affecting cancer patients with advanced disease. The current therapy for MPE is local treatment, such as thoracentesis, chemical pleurodesis, intracavitary administration of anticancer drugs and systemic therapy. However, the management of MPE is still unsatisfactory. Case: We report a case of MPE secondary to human epidermal growth factor receptor 2 (HER2)-positive gastric cancer that was successfully treated with intrapleural trastuzumab. A 52-year-old male with metastatic HER2positive gastric cancer received chemotherapy (FOLFOX4 regimen) plus trastuzumab; after 11 courses of chemotherapy, he developed right MPE refractory to systemic treatment and pleurodesis. A pleural biopsy performed during thoracoscopy showed pleural metastasis from HER2-positive gastric cancer. The patient received 2 courses of intrapleuric trastuzumab. After the second course, the MPE disappeared, and he continued systemic therapy with trastuzumab and docetaxel. Conclusion: The safety was good, no local or sys-
© 2015 S. Karger AG, Basel 0009–3157/15/0606–0321$39.50/0 E-Mail [email protected] www.karger.com/che
temic complications occurred, and the dyspnea secondary to MPE improved and subsequently disappeared. To our knowledge, this case is the first report on intrapleuric trastuzumab use to treat refractory MPE secondary to metastasis from HER2-positive gastric cancer. The treatment was welltolerated and efficacious. © 2015 S. Karger AG, Basel
Introduction
Malignant pleural effusion (MPE) is an extremely common problem affecting cancer patients with advanced disease [1]. In metastatic gastric cancer, patients with pleural or lymphangitic metastasis have shorter survival with a 1.5- to 2-fold increased risk of death [2]. In these cases, we need more effective treatment since the progression of the disease is rapid and symptoms such as cough, dyspnea and thoracic pain can rapidly affect quality of life. The current therapy for MPE is local treatment, such as thoracentesis, chemical pleurodesis, intracavitary administration of anticancer drugs and systemic therapy [3]. However, the management of MPE is still unsatisfactory. Trastuzumab is a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) that was Luigi Cavanna Department of Oncology-Hematology Ospedale Guglielmo da Saliceto via Taverna 49, 29121 Piacenza (Italy) E-Mail l.cavanna @ ausl.pc.it
Downloaded by: UCONN Storrs 198.143.38.1 - 1/26/2016 10:37:32 PM
Color version available online
Fig. 1. Pleural biopsy: tumor cells exhibit
strong membrane staining with a basal-lateral pattern with HER2 immunostain (HER2 DACO© polyclonal antibody ×20).
Case Report In May 2014, a 57-year-old man who had abdominal pain underwent gastroscopy. The biopsy result showed an intestinal-type gastric adenocarcinoma; on the immunohistochemical analysis, the HER2 status was positive (score 3+). Abdominal and thoracic computed tomography showed gastric and peritoneal disease. Eastern Cooperative Oncology Group performance status was 1 and the patient was treated with FOLFOX4 regimen [7, 8] in association with trastuzumab (a load dose of 8 mg/kg and maintenance dose of 6 mg/kg) every 3 weeks. After 11 cycles of FOLFOX4 plus trastuzumab, the computed tomography scan evaluation showed a partial response. Two
322
Chemotherapy 2014;60:321–324 DOI: 10.1159/000437136
months later, the patient presented with dyspnea; a chest X-ray showed median-basal right pleural fluid constricting the lung parenchyma. A second-line chemotherapy with docetaxel (75 mg/ mg every 3 weeks) plus trastuzumab was started. However, the dyspnea worsened and the patient was admitted to hospital; he underwent right ultrasonography-guided thoracentesis and 1,800 ml of hematic fluid was removed. Cytological examination showed metastasis from gastric cancer. Seven days later, he presented with dyspnea again and a second thoracentesis was performed, with 1,900 ml of fluid being removed. Thoracoscopy with pleural biopsies and pleurodesis were then carried out. Histological samples showed HER2-positive metastasis to the pleura from gastric cancer (fig. 1). Throughout pleurodesis, the pleural effusion persisted, and the patient presented with worsening dyspnea with the production of pleural hematic fluid (300–600 ml daily), despite constant pleural drainage. So, after obtaining informed consent, we decided to administer trastuzumab intrapleurally. The treatment consisted of trastuzumab administration on days 1 and 3 (a dose of 150 mg diluted in 50 ml saline water), 1 h after the systemic premedication of corticosteroids and antiemetic therapy. The administration took place by bolus. On the 2 days after the first administration, the daily amount of pleural fluid produced was 50 and 20 ml, respectively. The day after the second intrapleural infusion, the production of pleural fluid ceased. Pleural drainage was stopped and the patient was discharged in a fair condition 3 days after the second intrapleural infusion. The treatment was well tolerated, and no local or adverse events occurred. Echocardiography was evaluated 1 day after the second administration: the systolic function was FE 50%. The patient was subsequently treated with systemic docetaxel plus trastuzumab.
Orlandi/Mordenti/Zangrandi/Cavanna
Downloaded by: UCONN Storrs 198.143.38.1 - 1/26/2016 10:37:32 PM
recently approved along with chemotherapy for the systemic treatment of advanced gastric cancer with HER2 positivity [4]. In advanced breast cancer, trastuzumab is used, and not only in systemic therapy, i.e. there are data showing the feasibility and safety of intrathecal administration of this drug for meningeal carcinomatosis [5]. We also know of a case of metastatic gastric cancer with peritoneal carcinomatosis where trastuzumab was administered intraperitoneally with a good response and safety profile [6]. We report on a case of HER2-positive metastatic gastric cancer with recidivant and refractory MPE that was successfully treated with intrapleural trastuzumab.
Discussion
The treatment of MPE is difficult, and locoregional and systemic therapy become important in this setting. The intrapleural administration of cytotoxic agents such as cisplatin, doxorubicin, etoposide and mytomycin C have all been reported and suggest some effectiveness, especially in case of drainage failure [9]. Nevertheless, the management of MPE is still unsatisfactory. Data on the use of intrapleural monoclonal antibodies for MPE are fragmentary and very poor. There have been reports on a combination of anti-VEGF bevacizumab and cisplatin for MPE secondary to lung cancer, and also on intrapleural instillation of the anti-CD20 monoclonal antibody, rituximab, in malignant lymphoma [10, 11]. The results, though based on a single case reports, were promising, showing good tolerance and safety. Trastuzumab, a monoclonal antibody targeting HER2, is a new standard option associated with chemotherapy for patients with HER2-positive, advanced gastric or gastro-oesophageal-junction cancer [4, 12]. Intrathecal administration of trastuzumab has been tested in some patients with HER2-positive breast cancer and with leptomeningeal carcinomatosis occurring after a systemic treatment [13, 14]. We previously reported the case of a patient with HER2 overexpression in gastric cancer; this patient developed leptomeningeal carcinomatosis and was treated with intrathecal trastuzumab [15]. Recently, the safety and efficacy of intraperitoneal trastuzumab administration in a patient with peritoneal carcinomatosis secondary to HER2-positive gastric cancer was also reported [6]. To the best to our knowledge, there are no reports on intrapleural trastuzumab administration for MPE sec-
ondary to pleural metastasis from gastric or breast cancer with HER2 overexpression. This is the first report on a patient with HER2-positive gastric cancer and MPE treated with intrapleural target therapy with trastuzumab showing efficacy and safety. It must be emphasized that the decision to treat this patient with intrapleural trastuzumab was based on (1) previous experiences of local disease control, (2) the interest shown by the patient to explore the opportunity of intrapleural treatment with target therapy, (3) the HER2 overexpression of pleural metastases and (4) the inefficacy of pleurodesis and systemic treatment with chemotherapy plus trastuzumab in MPE. We are aware that no data exist on the use of an adequate dose and the frequency of intrapleural trastuzumab administration. We applied the regime used in the treatment of leptomeningeal carcinomatosis in HER2-positive breast cancer and in the case with peritoneal carcinomatosis. A month after the second intrapleural infusion, the patient was well, had no MPE and continued systemic treatment with trastuzumab plus chemotherapy.
Acknowledgements We would like to acknowledge the AMOP teams and supporters of Pontenure, Pianello, Podenzano, Cortemaggiore and Ferriere.
Disclosure Statement None of the authors has any conflict of interest to declare regarding this study.
References
Intrapleural Trastuzumab Therapy
small-cell lung cancer: a multi-institutional phase II trial. Br J Cancer 2006; 95: 717–721. 4 Bang YJ, Van Custem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüchoff J, Kang YK: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687–697. 5 Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M: Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive
metastatic breast cancer: a systematic review and pooled analysis. Breast Cancer Res Treat 2013;139:13–22. 6 Berretta M, Fisichella R, Borsatti E, Lleshi A, Ioffredo S, Meneguzzo N, Canzonieri V, Di Grazia A, Cannizzaro R, Tirelli U, Berretta S: Feasibility of intraperitoneal trastuzumab treatment in a patient with peritoneal carcinomatosis from gastric cancer. Eur Rev Med Pharmacol Sci 2014; 18: 689–692. 7 Cavanna L, Artioli F, Codignola C, Lazzaro A, Rizzi A, Gamboni A, Rota L, Rodinò C, Boni F, Iop A, Zaniboni A: Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC). Am J Clin Oncol 2006; 29: 371–375.
Chemotherapy 2014;60:321–324 DOI: 10.1159/000437136
323
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1 Cavanna L, Mordenti P, Bertè R, Palladino MA, Biasini C, Anselmi E, Seghini P, Vecchia S, Civardi G, Di Nunzio C: Ultrasound guidance reduces pneumothorax rate and improves safety of thoracentesis in malignant pleural effusion: report on 445 consecutive patients with advanced cancer. World J Surg Oncol 2014;12:139. 2 Jee HK, Lee J, Yi CA, Park SH, Park JO, Park YS, Lim HY, Park KW, Kang WK: Lung metastases in metastatic gastric cancer: pattern of lung metastases and clinical outcome. Gastric Cancer 2012;15:292–298. 3 Seto T, Ushijima S, Yamamoto H, Ito K, Araki J, Inoue Y, Semba H, Ichinose Y: Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-
324
pleural effusion. Oncol Rep 2013; 29: 2332– 2340. 11 Tadmor T, Polliack A: Rituximab in space: intrapleural and other novel routes of administration for lymphomas and lymphoid leukemias. Leuk Lymphoma 2012;53:5–7. 12 Moelans CB, van Diest PJ, Milne AN, Offerhaus GJ: Her-2/neu testing and therapy in gastroesophageal adenocarcinoma. Patholog Res Int 2010;2011:674182. 13 Platini C, Long J, Walter S: Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab. Lancet Oncol 2006; 7: 778–780.
Chemotherapy 2014;60:321–324 DOI: 10.1159/000437136
14 Stemmler HJ, Mengele K, Schmitt M, Harbeck N, Laessig D, Herrmann KA, Schaffer P, Heinemann V: Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report. Anticancer Drugs 2008; 19: 832–836. 15 Cavanna L, Rocchi A, Gorgni S, Ambroggi M, Foroni RP, Ubiali A, Civardi G: Cerebrospinal fluid cytology diagnosis of HER2-positive leptomeningeal carcinomatosis from HER2positive metastatic gastric cancer: case report. J Clin Oncol 2011;29:367–368.
Orlandi/Mordenti/Zangrandi/Cavanna
Downloaded by: UCONN Storrs 198.143.38.1 - 1/26/2016 10:37:32 PM
8 Yeh YS, Tsai HL, Ma CJ, Wu DC, Lu Cy, Wu IC, Hou MF, Wang JY: A retrospective study of safety and efficacy of a first-line treatment with modified FOLFOX-4 in unresectable advanced or recurrent gastric cancer patients. Chemotherapy 2012; 5: 411– 418. 9 Haas AR, Sterman DH: Intracavitary therapeutics for pleural malignancies. Clin Chest Med 2013;34(3): 501–513. 10 Du N, Li X, Li F, Zhao H, Fan Z, Ma J, Fu Y, Kang H: Intrapleural combination therapy with bevacizumab and cisplatin for nonsmall cell lung cancer-mediated malignant
Chemotherapy 2014;60:321–324 DOI: 10.1159/000437136
Intrapleural Trastuzumab Therapy for Malignant Pleural Effusion from HER2 Overexpression in Metastatic Gastric Cancer Elena Orlandi a Patrizia Mordenti a Adriano Zangrandi b Luigi Cavanna a
Departments of a Oncology-Hematology and b Pathology, Ospedale Guglielmo da Saliceto, Piacenza, Italy
Key Words Malignant pleural effusion · Trastuzumab · Gastric cancer · HER2 overexpression
Abstract Background: Malignant pleural effusion (MPE) is an extremely common problem affecting cancer patients with advanced disease. The current therapy for MPE is local treatment, such as thoracentesis, chemical pleurodesis, intracavitary administration of anticancer drugs and systemic therapy. However, the management of MPE is still unsatisfactory. Case: We report a case of MPE secondary to human epidermal growth factor receptor 2 (HER2)-positive gastric cancer that was successfully treated with intrapleural trastuzumab. A 52-year-old male with metastatic HER2positive gastric cancer received chemotherapy (FOLFOX4 regimen) plus trastuzumab; after 11 courses of chemotherapy, he developed right MPE refractory to systemic treatment and pleurodesis. A pleural biopsy performed during thoracoscopy showed pleural metastasis from HER2-positive gastric cancer. The patient received 2 courses of intrapleuric trastuzumab. After the second course, the MPE disappeared, and he continued systemic therapy with trastuzumab and docetaxel. Conclusion: The safety was good, no local or sys-
© 2015 S. Karger AG, Basel 0009–3157/15/0606–0321$39.50/0 E-Mail [email protected] www.karger.com/che
temic complications occurred, and the dyspnea secondary to MPE improved and subsequently disappeared. To our knowledge, this case is the first report on intrapleuric trastuzumab use to treat refractory MPE secondary to metastasis from HER2-positive gastric cancer. The treatment was welltolerated and efficacious. © 2015 S. Karger AG, Basel
Introduction
Malignant pleural effusion (MPE) is an extremely common problem affecting cancer patients with advanced disease [1]. In metastatic gastric cancer, patients with pleural or lymphangitic metastasis have shorter survival with a 1.5- to 2-fold increased risk of death [2]. In these cases, we need more effective treatment since the progression of the disease is rapid and symptoms such as cough, dyspnea and thoracic pain can rapidly affect quality of life. The current therapy for MPE is local treatment, such as thoracentesis, chemical pleurodesis, intracavitary administration of anticancer drugs and systemic therapy [3]. However, the management of MPE is still unsatisfactory. Trastuzumab is a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2) that was Luigi Cavanna Department of Oncology-Hematology Ospedale Guglielmo da Saliceto via Taverna 49, 29121 Piacenza (Italy) E-Mail l.cavanna @ ausl.pc.it
Downloaded by: UCONN Storrs 198.143.38.1 - 1/26/2016 10:37:32 PM
Color version available online
Fig. 1. Pleural biopsy: tumor cells exhibit
strong membrane staining with a basal-lateral pattern with HER2 immunostain (HER2 DACO© polyclonal antibody ×20).
Case Report In May 2014, a 57-year-old man who had abdominal pain underwent gastroscopy. The biopsy result showed an intestinal-type gastric adenocarcinoma; on the immunohistochemical analysis, the HER2 status was positive (score 3+). Abdominal and thoracic computed tomography showed gastric and peritoneal disease. Eastern Cooperative Oncology Group performance status was 1 and the patient was treated with FOLFOX4 regimen [7, 8] in association with trastuzumab (a load dose of 8 mg/kg and maintenance dose of 6 mg/kg) every 3 weeks. After 11 cycles of FOLFOX4 plus trastuzumab, the computed tomography scan evaluation showed a partial response. Two
322
Chemotherapy 2014;60:321–324 DOI: 10.1159/000437136
months later, the patient presented with dyspnea; a chest X-ray showed median-basal right pleural fluid constricting the lung parenchyma. A second-line chemotherapy with docetaxel (75 mg/ mg every 3 weeks) plus trastuzumab was started. However, the dyspnea worsened and the patient was admitted to hospital; he underwent right ultrasonography-guided thoracentesis and 1,800 ml of hematic fluid was removed. Cytological examination showed metastasis from gastric cancer. Seven days later, he presented with dyspnea again and a second thoracentesis was performed, with 1,900 ml of fluid being removed. Thoracoscopy with pleural biopsies and pleurodesis were then carried out. Histological samples showed HER2-positive metastasis to the pleura from gastric cancer (fig. 1). Throughout pleurodesis, the pleural effusion persisted, and the patient presented with worsening dyspnea with the production of pleural hematic fluid (300–600 ml daily), despite constant pleural drainage. So, after obtaining informed consent, we decided to administer trastuzumab intrapleurally. The treatment consisted of trastuzumab administration on days 1 and 3 (a dose of 150 mg diluted in 50 ml saline water), 1 h after the systemic premedication of corticosteroids and antiemetic therapy. The administration took place by bolus. On the 2 days after the first administration, the daily amount of pleural fluid produced was 50 and 20 ml, respectively. The day after the second intrapleural infusion, the production of pleural fluid ceased. Pleural drainage was stopped and the patient was discharged in a fair condition 3 days after the second intrapleural infusion. The treatment was well tolerated, and no local or adverse events occurred. Echocardiography was evaluated 1 day after the second administration: the systolic function was FE 50%. The patient was subsequently treated with systemic docetaxel plus trastuzumab.
Orlandi/Mordenti/Zangrandi/Cavanna
Downloaded by: UCONN Storrs 198.143.38.1 - 1/26/2016 10:37:32 PM
recently approved along with chemotherapy for the systemic treatment of advanced gastric cancer with HER2 positivity [4]. In advanced breast cancer, trastuzumab is used, and not only in systemic therapy, i.e. there are data showing the feasibility and safety of intrathecal administration of this drug for meningeal carcinomatosis [5]. We also know of a case of metastatic gastric cancer with peritoneal carcinomatosis where trastuzumab was administered intraperitoneally with a good response and safety profile [6]. We report on a case of HER2-positive metastatic gastric cancer with recidivant and refractory MPE that was successfully treated with intrapleural trastuzumab.
Discussion
The treatment of MPE is difficult, and locoregional and systemic therapy become important in this setting. The intrapleural administration of cytotoxic agents such as cisplatin, doxorubicin, etoposide and mytomycin C have all been reported and suggest some effectiveness, especially in case of drainage failure [9]. Nevertheless, the management of MPE is still unsatisfactory. Data on the use of intrapleural monoclonal antibodies for MPE are fragmentary and very poor. There have been reports on a combination of anti-VEGF bevacizumab and cisplatin for MPE secondary to lung cancer, and also on intrapleural instillation of the anti-CD20 monoclonal antibody, rituximab, in malignant lymphoma [10, 11]. The results, though based on a single case reports, were promising, showing good tolerance and safety. Trastuzumab, a monoclonal antibody targeting HER2, is a new standard option associated with chemotherapy for patients with HER2-positive, advanced gastric or gastro-oesophageal-junction cancer [4, 12]. Intrathecal administration of trastuzumab has been tested in some patients with HER2-positive breast cancer and with leptomeningeal carcinomatosis occurring after a systemic treatment [13, 14]. We previously reported the case of a patient with HER2 overexpression in gastric cancer; this patient developed leptomeningeal carcinomatosis and was treated with intrathecal trastuzumab [15]. Recently, the safety and efficacy of intraperitoneal trastuzumab administration in a patient with peritoneal carcinomatosis secondary to HER2-positive gastric cancer was also reported [6]. To the best to our knowledge, there are no reports on intrapleural trastuzumab administration for MPE sec-
ondary to pleural metastasis from gastric or breast cancer with HER2 overexpression. This is the first report on a patient with HER2-positive gastric cancer and MPE treated with intrapleural target therapy with trastuzumab showing efficacy and safety. It must be emphasized that the decision to treat this patient with intrapleural trastuzumab was based on (1) previous experiences of local disease control, (2) the interest shown by the patient to explore the opportunity of intrapleural treatment with target therapy, (3) the HER2 overexpression of pleural metastases and (4) the inefficacy of pleurodesis and systemic treatment with chemotherapy plus trastuzumab in MPE. We are aware that no data exist on the use of an adequate dose and the frequency of intrapleural trastuzumab administration. We applied the regime used in the treatment of leptomeningeal carcinomatosis in HER2-positive breast cancer and in the case with peritoneal carcinomatosis. A month after the second intrapleural infusion, the patient was well, had no MPE and continued systemic treatment with trastuzumab plus chemotherapy.
Acknowledgements We would like to acknowledge the AMOP teams and supporters of Pontenure, Pianello, Podenzano, Cortemaggiore and Ferriere.
Disclosure Statement None of the authors has any conflict of interest to declare regarding this study.
References
Intrapleural Trastuzumab Therapy
small-cell lung cancer: a multi-institutional phase II trial. Br J Cancer 2006; 95: 717–721. 4 Bang YJ, Van Custem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüchoff J, Kang YK: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 2010;376:687–697. 5 Zagouri F, Sergentanis TN, Bartsch R, Berghoff AS, Chrysikos D, de Azambuja E, Dimopoulos MA, Preusser M: Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive
metastatic breast cancer: a systematic review and pooled analysis. Breast Cancer Res Treat 2013;139:13–22. 6 Berretta M, Fisichella R, Borsatti E, Lleshi A, Ioffredo S, Meneguzzo N, Canzonieri V, Di Grazia A, Cannizzaro R, Tirelli U, Berretta S: Feasibility of intraperitoneal trastuzumab treatment in a patient with peritoneal carcinomatosis from gastric cancer. Eur Rev Med Pharmacol Sci 2014; 18: 689–692. 7 Cavanna L, Artioli F, Codignola C, Lazzaro A, Rizzi A, Gamboni A, Rota L, Rodinò C, Boni F, Iop A, Zaniboni A: Oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic gastric cancer (MGC). Am J Clin Oncol 2006; 29: 371–375.
Chemotherapy 2014;60:321–324 DOI: 10.1159/000437136
323
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1 Cavanna L, Mordenti P, Bertè R, Palladino MA, Biasini C, Anselmi E, Seghini P, Vecchia S, Civardi G, Di Nunzio C: Ultrasound guidance reduces pneumothorax rate and improves safety of thoracentesis in malignant pleural effusion: report on 445 consecutive patients with advanced cancer. World J Surg Oncol 2014;12:139. 2 Jee HK, Lee J, Yi CA, Park SH, Park JO, Park YS, Lim HY, Park KW, Kang WK: Lung metastases in metastatic gastric cancer: pattern of lung metastases and clinical outcome. Gastric Cancer 2012;15:292–298. 3 Seto T, Ushijima S, Yamamoto H, Ito K, Araki J, Inoue Y, Semba H, Ichinose Y: Intrapleural hypotonic cisplatin treatment for malignant pleural effusion in 80 patients with non-
324
pleural effusion. Oncol Rep 2013; 29: 2332– 2340. 11 Tadmor T, Polliack A: Rituximab in space: intrapleural and other novel routes of administration for lymphomas and lymphoid leukemias. Leuk Lymphoma 2012;53:5–7. 12 Moelans CB, van Diest PJ, Milne AN, Offerhaus GJ: Her-2/neu testing and therapy in gastroesophageal adenocarcinoma. Patholog Res Int 2010;2011:674182. 13 Platini C, Long J, Walter S: Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab. Lancet Oncol 2006; 7: 778–780.
Chemotherapy 2014;60:321–324 DOI: 10.1159/000437136
14 Stemmler HJ, Mengele K, Schmitt M, Harbeck N, Laessig D, Herrmann KA, Schaffer P, Heinemann V: Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report. Anticancer Drugs 2008; 19: 832–836. 15 Cavanna L, Rocchi A, Gorgni S, Ambroggi M, Foroni RP, Ubiali A, Civardi G: Cerebrospinal fluid cytology diagnosis of HER2-positive leptomeningeal carcinomatosis from HER2positive metastatic gastric cancer: case report. J Clin Oncol 2011;29:367–368.
Orlandi/Mordenti/Zangrandi/Cavanna
Downloaded by: UCONN Storrs 198.143.38.1 - 1/26/2016 10:37:32 PM
8 Yeh YS, Tsai HL, Ma CJ, Wu DC, Lu Cy, Wu IC, Hou MF, Wang JY: A retrospective study of safety and efficacy of a first-line treatment with modified FOLFOX-4 in unresectable advanced or recurrent gastric cancer patients. Chemotherapy 2012; 5: 411– 418. 9 Haas AR, Sterman DH: Intracavitary therapeutics for pleural malignancies. Clin Chest Med 2013;34(3): 501–513. 10 Du N, Li X, Li F, Zhao H, Fan Z, Ma J, Fu Y, Kang H: Intrapleural combination therapy with bevacizumab and cisplatin for nonsmall cell lung cancer-mediated malignant
