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The role of the liposomal anthracyclines and other systemic therapies in the management of advanced breast cancer.

Abstract：

:For patients whose breast cancers are not responsive to endocrine therapy, there are a large number of cytotoxic drugs that will induce a response. In spite of the introduction of new, very active drugs such as the taxanes, vinorelbine, capecitabine, gemcitabine, and trastuzumab, the anthracyclines are still as active as any--and more active than most--drugs used to treat breast cancer. Their inclusion in combinations to treat early and advanced disease prolongs survival. However, they cause nausea, vomiting, alopecia, myelosuppression, mucositis, and cardiomyopathies. There is no evidence that increasing the dose of conventional anthracyclines or any other of the cytotoxics beyond standard doses will improve outcomes. Schedule may be more important than dose in determining the benefit of cytotoxics used to treat breast cancer. Weekly schedules and continuous infusions of 5-fluorouracil and doxorubicin may have some advantages over more intermittent schedules. Liposomal formations of doxorubicin reduce toxicity, including cardiotoxicity; theoretically they should also be more effective because of better targeting of tumor over normal tissues. Both pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]) and liposomal doxorubicin (Myocet [NPLD]) appeared to be as effective as conventional doxorubicin and much less toxic in multiple phase II and phase III studies. PLD has been evaluated in combinations with cyclophosphamide, the taxanes, vinorelbine, gemcitabine, and trastuzumab, and NPLD has been evaluated in combination with cyclophosphamide and trastuzumab. Both liposomal anthracyclines are less cardiotoxic than conventional doxorubicin. The optimal dose of PLD is lower than that of conventional doxorubicin or NPLD. Patients treated with PLD have almost no alopecia, nausea, or vomiting, but its use is associated with stomatitis and hand-foot syndrome, which can be avoided or minimized with the use of proper dose-schedules. In contrast, the optimal dose-schedule of NPLD is nearly identical to that of conventional doxorubicin. The toxicity profile of NPLD is similar to that of conventional doxorubicin, but toxicities are less severe and NPLD is better tolerated than conventional doxorubicin at higher doses.

journal_name

Semin Oncol

journal_title

Seminars in oncology

authors

Robert NJ,Vogel CL,Henderson IC,Sparano JA,Moore MR,Silverman P,Overmoyer BA,Shapiro CL,Park JW,Colbern GT,Winer EP,Gabizon AA

doi

10.1053/j.seminoncol.2004.09.018

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

106-46

issue

6 Suppl 13

eissn

0093-7754

issn

1532-8708

pii

S0093-7754(04)00415-4

journal_volume

pub_type

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The role of the liposomal anthracyclines and other systemic therapies in the management of advanced breast cancer.