title: Optimal sequence of anthracyclines and taxanes as adjuvant breast cancer treatment.
abstract: Results from randomized trials evaluating taxane versus non-taxane containing regimens in adjuvant breast cancer treatment indicate an advantage in DFS and OS for the taxane-arms, but the best schedule of administration, in combination with anthracyclines or in sequence, is still a debated issue, even if the sequential strategy appears to be less toxic. Up to now, the majority of clinical trials employed the "standard" sequence, with anthracycline-based combinations fi rst, followed by taxanes. Few small phase II trials evaluated the reverse sequence, with taxanes administered fi rst, most of them in metastatic or neoadjuvant setting, suggesting efficacy and lower toxicity. An important issue to be considered is the hypothesized differences in the ability of the drugs to induce cross-resistance to each other, as suggested by data of a preclinical study, and from clinical study with a cross-over design; results of these trials suggest that the best strategy would be to administer a taxane prior to an anthracycline, also according to the Norton and Simon hypothesis. Moreover, trials evaluating the best sequence of anthracyclines and taxanes in adjuvant breast cancer setting are of small sample size, and an adequately powered randomized phase III trial is needed before definitive conclusions are reached.
authors.affiliation: Istituto Nazionale Tumori Regina Elena, Roma. pvici@ifo.it
authors.forename: P
authors.initials: P
authors.lastname: Vici
authors.forename: G
authors.initials: G
authors.lastname: Viola
authors.forename: S
authors.initials: S
authors.lastname: Rossi
authors.forename: C
authors.initials: C
authors.lastname: Botti
authors.forename: C
authors.initials: C
authors.lastname: Vitucci
authors.forename: D
authors.initials: D
authors.lastname: Sergi
authors.forename: F R
authors.initials: FR
authors.lastname: Ferranti
authors.forename: E
authors.initials: E
authors.lastname: Saracca
authors.forename: L
authors.initials: L
authors.lastname: Di Lauro
authors.forename: S
authors.initials: S
authors.lastname: Corsetti
authors.forename: P
authors.initials: P
authors.lastname: Foggi
authors.forename: S I S
authors.initials: SI
authors.lastname: Fattoruso
authors.forename: M
authors.initials: M
authors.lastname: Lopez
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D018592:Cross-Over Studies; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D043823:Taxoids; D015251:Epirubicin; D004317:Doxorubicin; D017239:Paclitaxel