Familial adenomatosis polyposis–related desmoid tumours treated with low-dose chemotherapy: results from an international, multi-institutional, retrospective analysis

Abstract

IntroductionDesmoid tumour (DT) is a locally aggressive fibroblastic proliferative disease representing the most common extraintestinal manifestation of familial adenomatosis polyposis (FAP). As data on the activity of chemotherapy in these patients are limited, we examined the outcomes of patients treated with low-dose methotrexate (MTX)+vinca alkaloids (vinorelbine or vinblastine).Patients and methodsWe retrospectively reviewed clinical and outcome data from all patients with confirmed FAP-associated DTs treated with weekly MTX+vinca alkaloids in seven European sarcoma reference centres between January 2000 and December 2018. Radiological responses were assessed using RECIST V.1.0 and V.1.1. The Kaplan-Meier method associated to the log-rank test was used to estimate and compare survival curves.ResultsWe identified 37 patients (median age 29 years, range 7–44). According to RECIST, 20/37 (54.1%) patients achieved partial response (PR), 15/37 (40.5%) patients had stable disease and 2/37 (5.4%) had progressive disease as best response. Overall, the median progression-free survival (PFS) was 6.5 years (range, 0.3–12.1 years). In the subset of patients achieving PR as best response, the median PFS was not reached. In a subset of 11 patients with progressive disease offered MTX+vinca alkaloids rechallenge (after chemotherapy withdrawal following prolonged disease control), the disease control rate was 100%, resulting in a median PFS after rechallenge of 5.8 years.ConclusionsThis is the largest series on the activity of low-dose chemotherapy in patients with FAP-related DT. In this population, MTX+vinca alkaloids is an active combination, as already reported in patients with sporadic DT.

Desmoid with biweekly methotrexate and vinblastine shows similar effects to weekly administration: A phase II clinical trial

“…Previous reports have not described symptomatic relief in detail other than that concerning pain. Three previous studies described that pain was reduced in almost all cases 11,18,25 . In the present study, pain was also reduced or disappeared in 76%, whereas ROM of the involved joint improved in only 33%.…”

“…Especially with weekly administration of MTX + VBL in an Asian cohort, neutropenia of grade 3 or higher was 33.3%, and liver transaminase elevations of all grades were 90.4%, necessitating reduction of the dose intensity 11 . Biweekly administration of MTX + VBL in the present study was associated with few grade 3/4 AEs, and elevated transaminases (all grades) in only 16%, indicating the relative paucity of AEs as compared with a weekly MTX + VBL regimen, 11,13 and an outcome of AEs similar to that with MTX + VNL 23,25 …”

“…Due to the small number of cases, there have been few reports on factors that effectively predict the effects of MTX + VBL chemotherapy. Clinical factors including age, gender, tumor size, and location, had no impact on the prediction of efficacy 24,25 . In the present study, we analyzed the clinicopathological factors including CTNNB1 status related to PR as a best response in univariate and multivariate models, despite the inadequate number of cases.…”

“…Several studies have reported the results of treatments combining MTX and vinca alkaloids for DF 10‐13,16‐18,23‐25 . The present study, which analyzed the results of 38 patients, is the largest ever using VBL as a vinca alkaloid.…”

“…Palassini et al 18 reported based on 30 patients receiving MTX + VBL therapy that response rate was 50% and CBR 97%. A multi‐institutional study in Europe for DF patients with FAP noted a response rate of 54% and CBR of 95% 25 . Efficacy as the best response was almost identical between the weekly and biweekly regimens.…”