Elsevier

Cancer Treatment Reviews

Volume 25, Issue 5, October 1999, Pages 279-291
Cancer Treatment Reviews

ANTITUMOUR TREATMENT
Current options in treatment of anthracycline-resistant breast cancer

https://doi.org/10.1053/ctrv.1999.0137Get rights and content

Abstract

Breast cancer is a chemosensitive tumour and anthracyclines are one of the most active cyctotoxic agents in chemotherapy treatment. Failure after anthracycline-containing chemotherapy is a poor prognostic factor because of low response rate to salvage chemotherapy. Several factors like P-glycoprotein mediated drug resistance (MDR-1 or MRP), glutathione or amplification of topoisomerase II have been found to be involved in anthracycline resistance. No clear benefit for patients treated with ‘resistance-modifier’ agents like verapamil, dexverapamil or quinidine has yet been demonstrated. Most clinical studies with non-cross resistant cytotoxic agents are laking a strict definition of anthracycline resistance. A strict definition of anthracycline resistance implies progessive disease during anthracycline chemotherapy. Among the cytotoxic drugs only 5-Fluorouracil (given as 24 h continous infusion with folinic acid) and the taxanes produce more than 20% objective remission (RR) in case of anthracycline resistance, whereas the highest response rate was reported for docetaxel (32–57%). Only few randomized studies were performed: docetaxel showed higher anti-tumor activity than methotrexat/5-FU (RR: 42% vs 19%, P<0.001) or mitomycin/vinblastine (RR: 30% vs 12%;P<0.001) and treatment with paclitaxel (175 mg/m2) was in favour to mitomycin (RR 17% vs 6%). In combination chemotherapy most activity have been reported for paclitaxel plus high-dose 5-fluorouracil (given as 24 h continous infusion with folinic acid) (RR: 58%) or for docetaxel plus cisplatinum (RR: 46%). High-dose regimens with growth factor or stem cell support seems to be active in anthracycline-resistant disease but the toxicity is considerable. In conclusion, the taxanes, especially docetaxel as single agent or paclitaxel plus high-dose 5-FU, are the most promising therapeutic options in treatment of anthracycline resistant disease. Further clinical phase II/III studies in breast cancer should include exact definition of anthracycline pretreatment and resistance.

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