Abstract CT121: Metronomic capecitabine and bevacizumab is an active combination in patients with relapsed peritoneal pseudomyxoma
Authors: Maggi Claudia , Pietrantonio Filippo , Di Bartolomeo Maria , Perrone Federica , Tamborini Elena , Milione Massimo , Deraco Marcello , Kusamura Shigeki , Baratti Dario , Berenato Rosa , Caporale Marta , Consonni Paola Valentina , Bossi Ilaria , Leo Ermanno , Pierotti Marco Alessandro , Gariboldi Manuela , Maggi Susanna , Pelosi Giuseppe , De Braud Filippo 
Published: August 2015

Abstract
Background: The standard treatment of peritoneal pseudomyxoma (PMP) is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma; modern chemotherapy regimens used in gastrointestinal malignancies may improve outcomes of these patients. The aim of our study was to assess the efficacy and safety of chemotherapy with metronomic capecitabine and bevacizumab in this subset of patients.
Materials and Methods: Patients were included in a single center, observational study and treated with metronomic capecitabine at the daily oral dose of 1300 mg/mq and intravenous bevacizumab at the dose of 7,5 mg/Kg every 3 weeks, until progressive disease or unacceptable toxicity.
All patients were relapsed after peritonectomy procedures and closed abdomen HIPEC with cisplatin and mitomycin C; six (43%) patients received one prior treatment line with FOLFOX-4 regimen (Pietrantonio et al., The Oncologist 2014). Ion Torrent® next generation sequencing technology (“Hot-spot Cancer Panel”) was used to obtain molecular data.
Results: Fourteen consecutive patients were included from February 2014 up today. Four patients are not evaluable for response because the treatment was started too early. Partial response was observed in one patient (10%), while radiological stable disease in all remaining 9 (90%). Most importantly, treatment was associated with a significant decrease of sierological markers (CEA, Ca19.9, Ca125) in all but one of evaluable patients. Median PFS was 7.3 months, while overall survival data are not mature. Safety data for this combination were consistent with the literature. By means of Ion-Torrent, 11 patients are evaluable. GNAS mutations were found in 4 (36%) cases and KRAS mutations in 10 (91%), while MGMT promoter methylation was found in 4 (36%). A rare mutation of HNFA1 was found in one case.
Conclusions: Metronomic capecitabine and bevacizumab combination is tolerable and active in patients with peritoneal pseudomyxoma when disease is relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers, such as KRAS for resistance to anti-epidermal growth factor receptor monoclonal antibodies and MGMT for response to temozolomide, is a priority for the development of evidence-based treatment strategies for this orphan disease.
Citation Format: Claudia Maggi, Filippo Pietrantonio, Maria Di Bartolomeo, Federica Perrone, Elena Tamborini, Massimo Milione, Marcello Deraco, Shigeki Kusamura, Dario Baratti, Rosa Berenato, Marta Caporale, Paola Valentina Consonni, Ilaria Bossi, Ermanno Leo, Marco Alessandro Pierotti, Manuela Gariboldi, Susanna Maggi, Giuseppe Pelosi, Filippo De Braud. Metronomic capecitabine and bevacizumab is an active combination in patients with relapsed peritoneal pseudomyxoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT121. doi:10.1158/1538-7445.AM2015-CT121