title: A randomized feasibility study of docetaxel versus vinorelbine in advanced breast cancer.
abstract: BACKGROUND
  Docetaxel and vinorelbine have demonstrated efficacy in the treatment of metastatic breast cancer (MBC). This prospective feasibility study compared the efficacy of these two treatments in MBC.
  
  
  METHODS
  Patients with MBC progressing following anthracycline treatment were randomly assigned to either docetaxel (100 mg/m(2)day 1 q3W) or vinorelbine (25mg/m(2) day 1 q2W). Patients were eligible to cross over at progression. Objective response rates (ORR), time to progression (TTP) and overall survival (OS) were measured.
  
  
  RESULTS
  37 patients were randomised. 2 patients were excluded due to protocol violations. Of 35 remaining patients 17 received docetaxel and 18 received vinorelbine per protocol. ORR was 12.5% and 6.0% respectively for docetaxel and vinorelbine. The median time to progression was 10.4 weeks (range 6-14 weeks) in docetaxel arm and 7.6 weeks (range 4-11 weeks) in vinorelbine arm (p = .82). The clinical benefit rate (defined as complete response, partial response plus stable disease) was 44% in the docetaxel arm and 12% in the vinorelbine arm. Based on intent to treat the median OS in the docetaxel arm was 34 weeks (95% CI, 20.7-48) and 21.2 weeks (95% CI, 17-25.4) in vinorelbine arm (p = .388). 16 patients crossed over, 5 from docetaxel to vinorelbine and 11 from vinorelbine to docetaxel. At cross over the ORR was 0% and 18% on cross over to vinorelbine and docetaxel respectively with a median TTP of 17.3 weeks (95% CI, 16.3-18.1) and 18.7 weeks (95% CI, 13.9-23.4) for those receiving vinorebine and docetaxel at cross over respectively. Vinorelbine however was much better tolerated with fewer grade 3-4 toxicity events (n = 4) than docetaxel (n = 27).
  
  
  CONCLUSIONS
  While docetaxel resulted in a longer TTP and OS in this study it did not reach statistical significance. TTP duration for those patients who crossed over was similar, but overwhelmingly vinorelbine had fewer significant grade 3-4 toxicities than docetaxel. Only two previous randomized studies have compared the efficacy of single agent docetaxel and vinorelbine following prior anthracycline exposure, one in an unselected population [16], and the other, HERNATA, in HER2 positive disease with trastuzumab used in both arms [17]. The patients randomized in this study were relatively heavily pretreated with the majority having received 2-3 lines of prior treatment for their metastatic disease. The lower response rates with vinorelbine as compared to docetaxel in this study concur with results reported in other studies [16]. However, the numbers in both this study and the other unselected study [16] are small and need to be interpreted with caution. With regard to toxicity, in the present study, grade 3-4 hematological adverse events and infection were tenfold greater with docetaxel as compared with vinorelbine, consistent with results in HERNATA [17]. While others have reported a significantly higher number of overall grade 3-4 toxicities with vinorelbine [16], the fact that, as in HERNATA, discontinuations due to toxicities in that study [16] were significantly greater with docetaxel as compared to vinorelbine suggests either the toxicity data collected did not reflect the true toxicities on treatment or that docetaxel toxicities were in some way more severe or protracted leading to more numerous discontinuations [16]. Larger randomized studies are needed to determine (1) the efficacy of docetaxel versus vinorelbine in anthracycline pretreated disease and (2) the efficacy of vinorelbine after prior taxane exposure, and particularly how it may compares both with regard to efficacy and tolerability with other possible regimens that may utilized such as carboplatin-gemcitabine [20] or eribulin [21]. The longer as well as comparable TTP at cross over for both agents compared to that upfront suggests there may be enrichment at cross over of a group of patients who are not only fit for further treatment but are more likely to a derive continued benefit from additional treatment.
authors.affiliation: Charing Cross Hospital, London, United Kingdom. c.palmieri@imperial.ac.uk
authors.forename: Carlo
authors.initials: C
authors.lastname: Palmieri
authors.forename: Constantine
authors.initials: C
authors.lastname: Alifrangis
authors.forename: David
authors.initials: D
authors.lastname: Shipway
authors.forename: Tri
authors.initials: T
authors.lastname: Tat
authors.forename: Vivienne
authors.initials: V
authors.lastname: Watson
authors.forename: Diane
authors.initials: D
authors.lastname: Mackie
authors.forename: Marie
authors.initials: M
authors.lastname: Emson
authors.forename: R Charles
authors.initials: RC
authors.lastname: Coombes
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D000077143:Docetaxel; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D000077235:Vinorelbine