Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei-A Novel Treatment Approach.

Aruna Prabhu,Satoshi Wakama,Nobuyuki Takao,Andreas Brandl,Shouzou Sako,Haruaki Ishibashi,Yutaka Yonemura,Yang Liu,Kousuke Noguchi,Masumi Ichinose,Akiyoshi Mizumoto,Shunsuke Motoi

doi:10.3390/cancers12082212

Abstract

Neoadjuvant intravenous chemotherapy in patients with pseudomyxoma peritonei (PMP) has not shown convincing results. The effectiveness of neoadjuvant intraperitoneal (IP) chemotherapy has never been reported. This prospective, non-randomized phase II study included patients with PMP treated between May 2017 and December 2018, who were not considered suitable for primary cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The majority of patients were treated with laparoscopic HIPEC (oxaliplatin 200 mg/m2, 60 min, 43 °C). IP chemotherapy was started 2 weeks after docetaxel 40 mg/m2 + cisplatin 40 mg/m2, accompanied by oral S1 (tegafur, gimeracil, and oteracil) (50 mg/m2) for 14 days, followed by one week rest. Clinical parameters and complications were recorded. In total, 22/27 patients qualified for CRS and HIPEC after neoadjuvant treatment. A complete cytoreduction (Completeness of cytoreduction Score 0/1) could be achieved in 54.5%. The postoperative morbidity rate was 13.6% and mortality was rate 4.5%. In total, 20/22 patients had major pathological tumor responses. The mean drop in CEA was 28.2% and in the peritoneal carcinomatosis index (PCI) was 2.6. Positive or suspicious cytology turned negative in 69.2% of patients. Thus, for PMP patients who were not amenable for primary surgery, the majority received complete cytoreduction after treatment with neoadjuvant IP chemotherapy, with satisfying tumor regression and with low complication rates. The oncological benefit in terms of survival with this new treatment regimen needs to be proven.

Highlights

Pseudomyxoma peritonei (PMP) is a clinical syndrome wherein the peritoneal cavity gets filled with free or organized mucin, with or without neoplastic cells
27 patients were included in the study and treated according to the therapeutic flowchart (Figure 1)
One patient was not treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) due to excellent response after 8 cycles of IP

Summary

Introduction

Pseudomyxoma peritonei (PMP) is a clinical syndrome wherein the peritoneal cavity gets filled with free or organized mucin, with or without neoplastic cells. In more than 90% of cases, the origin of PMP is a ruptured mucinous appendiceal tumor [1,2] The tendency of these tumors to remain confined to the peritoneal cavity makes them amenable for treatment with aggressive loco-regional therapies. In the 1990s, before the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), the treatment for PMP mainly comprised repeated drainage of mucin or palliative debulking surgery, with or without palliative chemotherapy. These treatment modalities were associated with a 10-year overall survival (OS) rate of approximately 20% [3,4]. With the introduction of CRS and HIPEC, the survival of these patients has greatly improved to reported 10- year OS rates of

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