Metronomic oral chemotherapy (CT) versus the same regimen in association with Thalidomide (TLM): results of a randomized trial in patients (pts) with advanced breast cancer (ABC)

Abstract

3015 Background: Clinical efficacy and antiangiogenic effect of low dose, continuous oral cyclophosphamide (CTX) and methotrexate (MTX) have been demonstrated. We hypothesized that the addition of TLM might further improve clinical response and modulate angiogenic factors in pts with ABC. Methods: Pts with ABC, either untreated or pretreated, were randomized to receive an oral schedule of MTX (2.5 mg orally, twice daily on day 1 and day 4) and CTX (50 mg, orally, daily) (arm A) or to receive the same regimen plus TLM (200mg, orally, daily) (arm B). Blood samples were collected at first visit and monthly to measure VEGF, bFGF, and circulating endothelial cells. Results: 178 pts were enrolled, 166 were evaluable for response. PS was 0 (150 patients), 1 (28 patients). Metastatic sites: lung (40 pts), liver (75 pts), bone (79 pts), lymph nodes (48 pts), and skin (20 pts). Median age was 54 (range 31–78). Progressive disease at study entry reported in 113 pts. Pts were stratified by preatreatment (no = 58; yes = 120). In the latter, 75 pts were pretreated with 1 line of CT, 45 pts with ≥ 2. Three CR in arm A and 4 in arm B, 17 PR in arm A and 9 in arm B for an overall response of 24% in arm A e 16% in arm B, SD was seen in 29 pts in arm A and 31 in arm B. The overall clinical benefit (CR+ PR+ SD >24 weeks) was 47% for both arms. PD was observed in 41% of pts in arm A and in 47% of pts in arm B. Overall clinical toxicity was generally mild. Grade ≥2 leucopenia was reported in 39 pts. Grade ≥2 thrombocytopenia appeared in 4 pts. Grade ≥2 liver toxicity was reported in 59 pts. No difference in terms of toxicity were observed between the 2 arms, with exception of more neurological toxicity (grade ≥2) and higher incidence of thromboembolic events in the TLM arm. In arm B twelve pts (14%) stopped TLM: 8 due to neurological toxicity grade 1–2, 2 due to hematological toxicity, 2 due to skin toxicity. Two pts in Arm B had a Grade 4 pancytopenia (1) and thromboembolism (1). Conclusions: Adding TLM to continuous, low-dose CTX and MTX did not increase clinical responses in pts with ABC. No significant financial relationships to disclose.