ORAL METRONOMIC CYCLOPHOSPHAMIDE IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER STRATIFIED BY PRIOR DOCETAXEL THERAPY

Abstract

Background: Treatment options remain limited for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Here we aimed to investigate the efficacy and safety of low-dose oral cyclophosphamide (CTX), an intermittent metronomic chemotherapy regimen, in pts with mCRPC, previously treated or not with docetaxel. Methods: All pts previously diagnosed with mCRPC and treated with CTX 100mg/ day (3 weeks on and 1 week off, every 28 days) plus prednisone 10mg/day between Oct/2006 and Feb/2012 at our institution were included in this retrospective analysis. The primary efficacy endpoint was prostate-specific antigen (PSA) decrease ≥ 50%. Secondary endpoints were PSA decrease ≥ 30% and toxicity. Kaplan-Meier estimates were calculated and plotted for time to treatment failure (TTF). Single and multivariate Cox proportional hazards modeling was used to estimate hazard ratios with 95% confidence intervals (95% CI). Results: 51 pts with mCRPC were identified, of which 30 (59%) had been already treated with docetaxel. The median age was 72 y.o. (56-86) and 27 pts (53%) were ECOG PS0-1 and 24 pts (47%) PS2-3. Five pts presented with visceral metastasis (10%) and median PSA 525 ng/dL (12-4099) before treatment. Median number of previous cytotoxic lines was 1 (0-2). After a median number of cycles CTX of 3, PSA decrease of ≥ 50% was achieved in 28.6% and 16.7% of docetaxel-naive and docetaxel-pretreated pts, respectively (p= 0.30). Besides, PSA declines of ≥ 30% occurred in 38.1% and 30.0% of docetaxel-naive and docetaxel-pretreated patients, respectively (p= 0.54). Overall, the median TTF was estimated to be 2.4 mo. (95% CI 1.87 – 3.73). Previously treatment with docetaxel was not statistically significant to TTF, and the median TTF was 2.1 mo. (95% CI 1.6 – 3.2) for docetaxel-pretreated and 3.4 mo. (95% CI 1.7 – 5.4) for docetaxel-naïve patients (HR 1.47; 95% CI 0.78 – 2.74; p = 0.22). In general, oral CTX was safe and well tolerated and the most commonly observed G3-4 AE was lymphopenia (29%). Conclusions: Oral metronomic CTX plus prednisone seems to be active and safe in mCRPC, even in pts previously treated with docetaxel. Its convenient oral administration, low cost, and acceptable toxicity profile may justify future investigations of this classic alkylating agent in mCRPC. Disclosure: All authors have declared no conflicts of interest.