FOLFOX-4 Chemotherapy for Patients With Unresectable or Relapsed Peritoneal Pseudomyxoma

Abstract

Purpose. The standard treatment of peritoneal pseudomyxoma 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. The aim of our study was to assess the activity of chemotherapy with 5‐fluorouracil and oxaliplatin (FOLFOX‐4 regimen) in terms of response rate in this subset of patients. Materials and Methods. Patients were included in a single‐center, observational study and treated with FOLFOX‐4 administered every 2 weeks for up to 12 cycles or until progressive disease or unacceptable toxicity. Results. Twenty consecutive patients were reviewed from July 2011 to September 2013. Only partial responses were observed, with an objective response rate of 20%. Median progression‐free survival and overall survival were 8 months and 26 months, respectively. Two patients were able to undergo laparotomy with complete cytoreduction and HIPEC in one case. Safety data for FOLFOX‐4 were consistent with the literature. By means of a mutant enriched polymerase chain reaction, KRAS mutation was found in 16 of 19 cases (84%), and MGMT promoter methylation was found in 8 (42%, all KRAS mutant). Conclusion. FOLFOX‐4 chemotherapy is tolerable and active in patients with peritoneal pseudomyxoma when disease is deemed unresectable or 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 peritoneal pseudomyxoma.

The impact of stage, grade, and mucinous histology on the efficacy of systemic chemotherapy in adenocarcinomas of the appendix: Analysis of the National Cancer Data Base

“…Because 41% of patients in the current study with stage IV, mucinous, well‐differentiated appendiceal adenocarcinoma received systemic chemotherapy as their first treatment, these data strongly support a change in clinical practice. Although a limited number of retrospective studies have evaluated chemotherapy for metastatic mucinous appendiceal adenocarcinomas, the interpretation of these data is inherently challenging due to the heterogeneity of behavior across histological grades and the indolent biology and generally good overall outcome for patients with well‐differentiated tumors . In what to our knowledge are the 2 largest retrospective reports evaluating systemic chemotherapy for appendiceal cancers, efficacy endpoints for chemotherapy were not analyzed across histological grades, and thus the impact of systemic chemotherapy for well‐differentiated as opposed to poorly differentiated tumor grades could not be determined .…”

Potential actionable targets in appendiceal cancer detected by immunohistochemistry, fluorescent in situ hybridization, and mutational analysis

“…Other histological variants include carcinoid or neuroendocrine and a mixed histology tumor of both carcinoid and adenocarcinoma subtype termed goblet cell carcinoma (5). Finally, another epithelial variant of appendiceal cancer is pseudomyxoma peritonei (PMP), a mucinous neoplasm that clinically presents as gelatinous ascites (6,7). Due to the rarity of these malignancies limited prospective trials exist guiding management.…”

“…A recent report from a single center, observational study used FOLFOX-4 as treatment for unresectable or relapsed PMP (7). Furthermore, MGMT methylation was assessed in 42% of these patients, indicating a potential response benefit to temozolomide (7). For carcinoid tumors of the appendix, guidelines recommend treatment to other gastrointestinal neuroendocrine tumors (16).…”

Systemic chemotherapy and survival in patients with metastatic low‐grade appendiceal mucinous adenocarcinoma

“…Although these regimens have improved survival in metastatic colorectal cancer, our analyses demonstrate that contemporary SC is not associated with OS in patients with metastatic low‐grade mucinous appendiceal adenocarcinoma. The indolent biology and slow growth of low‐grade appendiceal neoplasms have been hypothesized to contribute to poor response to cell‐cycle specific systemic chemotherapy agents …”