Susceptibility of Fibromatosis Cells in Short‐Term Culture to Ifosfamide: A Possible Experimental Treatment in Clinically Aggressive Cases

Mark W Verrill,Helen M Coley,Cyril Fisher,Ian R Judson

doi:10.1080/13577149977686

Abstract

Purpose. Deep fibromatoses are large, often rapidly growing but benign soft tissue tumours. Although surgery is the mainstay of treatment, in unremitting and aggressive cases the use of cytotoxic chemotherapy may produce objective tumour responses. Fresh tumour samples from four patients with fibromatosis were investigated as part of a study of drug resistance in soft tissue tumours. Methods. Following short-term culture of fibromatosis cells in vitro , chemosensitivity to 4-hydroperoxy-ifosfamide, the active form of ifosfamide and doxorubicin was tested. Following 72-h continuous exposure to each drug, surviving cell fraction was assessed using the lactate dehydrogenase assay. Results. Mean IC50 values for ifosfamide and doxorubicin were 6.2 and 0.35 µmol/l, respectively. In samples of soft tissue sarcoma (STS) from the same study the mean IC50 values for ifosfamide and doxorubicin were 14.8 and 1.69 µmol. The difference in mean ifosfamide IC50 values for fibromatosis and STS samples was statistically significant. Discussion. We are not aware of any other report suggesting the use of ifosfamide in this condition. These observations suggest that, for patients with inoperable or progressive lesions of fibromatosis causing significant morbidity, it may be valuable to include ifosfamide in experimental treatment regimens.

Highlights

The deep ® bromatoses, known as desmoid tumours, are large, often rapidly growing but benign soft tissue tumours
We are not aware of any other report suggesting the use of ifosfamide in this condition
Abdominal ® bromatosis arises from the m usculo-aponeurotic structures of the abdominal wall and tends to occur in women of child bearing age during or after pregnancy, leading to the hyp othesis that horm onal factors are important in the aetiology of the condition

Summary

Results

Out of 97 fresh tissue samples collected, the diagnosis of ® brom atosis was m ade in four cases. Mann± W hitney U-test there was a signi® cant difference between the IC50 values in STS and ® brom atosis for ifosfam ide (p < 0.01) but not for doxorubicin (p = 0.1). A widely used chem otherapy strategy is thePhiladelphia’ regim en of low-dose weekly methotrexate (50 mg/week) and vinblastine (10 m g/week).[20,22] The activity of m ore aggressive regimens based on doxorubicin and dacarba z in ehasa lso beendemon strat e d 21,23,27 an d in children, the com bination of dacarbazine with vincristine and cyclophospham ide (VAC) has been shown to be effective.[28] We did not have sufficient clinical material available to test ® bromatosis cells against these other cytotoxic drugs. H ow eve r, fo r patien ts w ith in o p erab le progressive lesions, causing signi® cant symptoms or posing a threat to normal organ function, it may be valuable to include ifosfam ide in experimental treatm ent regim ens

Introduction

Methods