Metronomic capecitabine plus cyclophosphamide in unresectable or relapsed pseudomyxoma peritonei

Background: The standard treatment of Pseudomyxoma Peritonei (PMP) is cytore ductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC).
No consensus was reached on treatment of unresectable or recurrent disease. PMP is
considered chemoresistant for its low mitotic index but non-randomized series
showed promising results with regimens for gastrointestinal tumors. Metronomic
schedules may be preferred for their antiangiogenic and immunomodulatory
activity.
Methods: We conducted a single center prospective single arm trial. Inclusion criteria
were histologically confirmed PMP, unresectable or relapsed after CRS/HIPEC, in
progression to surgery or previous treatments. Patients received continuous metro nomic capecitabine (625 mg/sqm b.i.d.) plus cyclophosphamide (50 mg/day) until
progressive disease, unacceptable toxicity or consent withdrawal. The primary end point was progression free survival (PFS); secondary endpoints were disease control
rate (DCR), overall survival (OS) and safety profile. Ion TorrentVR next generation
sequencing technology (Hot-spot Cancer Panel) was used to characterize molecular
profile.
Results: 23 consecutive patients were enrolled from April 2015 to October 2017. At a
median follow up of 13.5 months, median PFS was 9.5 months and 1-year OS rate 73.7%
(95% CI 47.3% - 88.3%). No partial or complete responses were observed but DCR was
74% and 22% patients achieved a prolonged disease stability (>13 months). A significant
tumor markers reduction (>20%) was seen in 43% patients for CA19.9, 22% for CA125
and 39% for CEA. The safety profile was manageable: 78% patients reported G1/2 drug
related adverse events, only 17% G3 and none G4/5. As expected, the main toxicities were
anemia, neutropenia, nausea, diarrhea, fatigue and hand foot syndrome. Only 17%
patients required capecitabine dose reduction. Molecular profile was available in 15/23
cases: KRAS mutations were found in all cases and GNAS mutations in 47%.
Conclusions: Metronomic capecitabine plus cyclophosphamide is an active and well
tolerated regimen in unresectable or recurrent PMP, with a safety profile comparing
favorably with historical data. Further studies are needed to identify predictive bio markers for novel treatment strategies