7.P.43 RESPONSE TO ANTIANGIOGENIC THERAPY WITH TROFOSFAMIDE AND BEVACIZUMAB IN A PATIENT WITH HEAVILY PRE-TREATED MALIGNANT FIBROUS HISTIOCYTOMA. EVALUATION OF RESPONSE VIA F18-PET-CT

Abstract

Palliative therapy of Malignant Fibrous Histiocytoma (MFH) is mainly based on conventional chemotherapy using anthracyclines and ifosfamide. Intervals between therapies allow abundant recovery of tumour vasculature. An unspecific antiangiogenic effect of chemotherapy can be induced by continuously administering low doses of drug referred to as Metronomic Chemotherapy (MCT). MCT may be combined with specific VEGF targeting drugs in order to increase the antiangiogenic impact on the tumour.

We report on a 57 y.o. male patient with heavily pre-treated advanced stage MFH. Previous polychemotherapies consisted of 8 cycles EIA in adjuvant setting in 2002, 4 cycles ICE in recurrent situation in 2003 and 6 cycles of Dacarbacine plus Epirubicine in 2006. In 2005 and 2006 radiation therapy of paravertebral tumour lesions was done. In September 2006 the patient was admitted to our hospital with multilocular metastatic progressive disease. Performance status was WHO1. A moderate asymptomatic anthracycline induced cardiomyopathy was detected. The cumulative dosage threshold for anthracyclines had been exceeded before. We initiated oral MCT with Trofosfamide 150 mg pd plus iv. – antiangiogenic therapy with Bevacizumab 5 mg/kg q 2w. Follow up (FU) was done via F18-PET-CT.

First FU after 8 weeks of combined therapy showed metabolic partial remission (PR) (48% decrease in mean Maximum Standard Uptake Valule (SUVmax) of target lesions) and metric stable disease (SD) (5% decrease in sum of diameters according to RECIST criteria). Trofosfamide was tolerated well. Treatment with Bevacizumab had to be stopped after 8 weeks because of symptomatic deterioration of cardiomyopathy (Ejection Fraction now 25%). Trofosfamide was continued as monotherapy. After 8 weeks of Trofosfamide alone PET-CT showed one new lesion indicating progressive disease according to RECIST but persistent metabolic remission of all pre-existing lesions. Bevacizumab then was added again but couldn’t stop further tumour progression (FU in March 2007). In summary disease control was achieved for 4 months. Combined metronomic and antiangiogenic therapy led to disease stabilisation and even metabolic remission measured by F18-PET-CT in a heavily pre-treated patient with soft tissue sarcoma. A pre-existing anthracycline-induced cardiomyopathy deteriorated under treatment with Bevacizumab. Whether response duration could have been prolonged by administering Bevacizumab without interruption remains speculative. The role of PET-CT in early detection of response is still to be determined.