METRONOMIC ORAL CYCLOPHOSPHAMIDE IN THE TREATMENT OF METASTATIC SOFT TISSUE SARCOMA: IS THERE A ROLE FOR MAINTENANCE THERAPY?

Abstract

Background Metronomic chemotherapy has been demonstrated to improve DFS in advanced STS. Here we aimed to analyze the efficacy and safety of metronomic oral cyclophosphamide (M-CTX) as maintenance or salvage therapy in these patients (pts). Methods It is a retrospective study of all advanced/metastatic STS pts (RMS, GIST, bone sarcomas excluded) treated in our institution between Feb/2009 and Jan/2012 with M-CTX 100 mg PO daily 21 out of 28 days, until disease progression (DP). Tumor response (RECIST 1.1) was assessed every 2 cycles. The primary endpoint of the study was time to treatment failure (TTF). Toxicity was graded according to the NCI-CTC v.3.0. criteria. Results 27 pts were consecutively included in this analysis. Thirteen pts received M-CTX as maintenance chemotherapy after presenting best response: median age 60 y, 9 female; 5 LMS, 3 HGUPS, 2 PNET, 3 others. Median number of previous chemotherapy regimens 2; 9 previously treated with doxorubicin and 4 with ifosfamide; 4 presented PR as best response. Median TTF (mTTF) was 9.2 mo, 4 pts (2 PNET, 1 LMS, 1 HGUPS) had mTTFs ≥ 6 mo and no deaths were observed in a median follow-up of 7 mo. 14 pts received M-CTX as salvage chemotherapy after DP: median age 45.5 y, 8 female; 3 LMS, 3 HGUPS, 3 synovial, 2 ASPS, 3 others. Median number of previous chemotherapy regimens 1.5; 11 previously treated with doxorubicin and 6 with ifosfamide; 1 PR as best response. mTTF 3.3 mo, 1 ASPS had mTTFs ≥ 6 mo, and 9 deaths (HR 1.403, 95%CI 0.608-3.236, p = 0.409, in comparison with maintenance strategy). In general, M-CTX was well tolerated, and the most common toxicity (>10%) included nausea G1 (5 pts), renal failure (3 pts), anemia G1 (4 pts), anemia G2 (3 pts), lymphopenia G1 (12 pts). Conclusions Metronomic oral cyclophosphamide seems to be a valid option as maintenance chemotherapy after presenting best response in advanced/metastatic STS, with acceptable toxicity. This compares favorably with historical controls (mPFS around 4 months). However, after disease progression, it is a futile chemotherapy regimen. Disclosure A.C.R. Ferrari: Travel expenses covered: Roche.