Cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy for metastatic breast cancer: a pilot study

Abstract

We assessed the activity and tolerability of a cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy in 28 advanced breast cancer patients. The schedule of treatment was as follows: 60 mg/ m2 epirubicin followed by 40 mg/m2 cisplatin given on days 1 and 2 every 21 days, with 450 mg lonidamine being given per os (three tablets) on days of chemotherapy administration and in the period intervening between one cycle and the next. Patients received a median of 5 (range 1-6) cycles. Overall, 22 patients were evaluable for response and 28, for toxicity. Four patients refused to continue the treatment after the first course, one was lost to follow-up, and one died due to toxicity (septic shock). The incidence of grade 3/4 nausea and vomiting was found to be greater than that expected with epirubicin and lonidamine alone. The addition of cisplatin resulted in an increase in platelet and hemoglobin toxicities, whereas the WBC toxicity did not differ from that expected with epirubicin and lonidamine. The hematological toxicity was found to be cumulative, leading to treatment delay in about 50% of patients at the fifth and sixth courses. The activity of this cytotoxic regimen was noteworthy, with the overall response rate being 81.8% (31.8% complete responses and 50.0% partial responses) in evaluable patients. This response rate decreased to 64.2% when all registered patients were included according to an intent-to-treat analysis. In conclusion, the association of cisplatin, epirubicin, and lonidamine given on the schedule described herein, appears to be very active but substantially toxic. We are now testing this combination in a randomized comparison, with the cisplatin dose being reduced to 30 mg/m2 given on days 1 and 2.

Independent Factors Predict Supranormal CA 15-3 Serum Levels in Advanced Breast Cancer Patients at First Disease Relapse

“…All patients underwent first-line chemotherapy with anthracycline alone (epirubicin) or anthracycline-containing schemes: epirubicin + lonidamine, epirubicin + cisplatin, epirubicin + cisplatin + lonidamine, epirubicin + paclitaxel [28][29][30]. In disease progression, patients received second-line chemotherapy or endocrine therapy according to standard or experimental protocols.…”

Lonidamine triggers apoptosis via a direct, Bcl-2-inhibited effect on the mitochondrial permeability transition pore

“…In preclinical studies, LND has been shown to exacerbate the response of human tumor cells to cisplatin (Angioli et al, 1997;DeCesare et al, 1998;Pratesi et al, 1996), irradiation (Dudak et al, 1996), doxorubicin (Pratesi et al, 1996), or cyclophosphamide (Pratesi et al, 1996). LND is used in phase II and III trials of metastatic breast cancer (Dogliotti et al, 1998) and ovarian cancer (DeLena et al, 1997). Similar to other anticancer drugs, LND kills cells by inducing apoptosis (Del Bufalo et al, 1996).…”

Mitomycin C, vinblastine and cisplatin (MVP): an active and well-tolerated salvage regimen for advanced breast cancer

“…Three studies have tested the combination of this drug with epirubicin plus or minus lonidamine and failed to show any substantial benefit from the addition of cisplatin (Gebbia et al, 1997;Dogliotti et al, 1998;Berruti et al, 2002). Despite being active (response rate of 73 -82% in first line), the addition of cisplatin did not result in clinical benefit and the toxicity was higher.…”