MODULATING EFFECT OF LONIDAMINE ON RESPONSE TO DOXORUBICIN IN METASTATIC BREAST-CANCER PATIENTS - RESULTS FROM A MULTICENTER PROSPECTIVE RANDOMIZED TRIAL

Previous results from our preclinical studies have shown that lonidami ne (LND) can positively modulate the antiproliferative activity of dox orubicin (DOX) on breast cancer cell lines. To evaluate the effect of LND in a clinical setting, a multicenter randomized trial was carried out on patients with advanced breast cancer. From September 1991 to Ju ly 1993, 181 patients were enrolled in the trial and received an initi al treatment of DOX at 75 mg/m(2) for 3 cycles. The 137 patients who r eached complete remission, partial remission, or stable disease were r andomized to receive either DOX alone (75 mg/m(2) day 1) (arm A) or DO X plus LND (600 mg orally/ day) (arm B). The patients enrolled in the two arms were fairly homogeneous in terms of major clinical characteri stics. Toxicity was similar in both arms except for myalgia: WHO grade greater than or equal to 2 was observed in 57% of arm B patients. Ove rall response rate to DO): + LND was 50% and to DOX alone 38% in evalu able patients, and 48% vs 37% in all registered patients, as determine d by an intention-to-treat analysis. The differences did not reach sta tistical significance. Conversely, in agreement with previous findings , we observed a significant difference in response rate in the subgrou p of patients with liver metastases, regardless of the extent of hepat ic involvement (DOX + LND 68% vs DOX 33%, p = 0.03). This observation makes LND an important tool in association with anthracyclines in the treatment of this subgroup of patients.