Weekly paclitaxel versus weekly docetaxel in elderly and frail patients with metastatic breast carcinoma having failed previous anthracyclines: a randomised phase II study of the Belgian Society of Medical Oncology.

Abstract

Abstract Abstract #6115 Rationale: Taxanes are considered as standard 2nd-line chemotherapy after anthracyclines in metastatic breast carcinoma (MBC). In one large randomized trial, Jones et al. (JCO 2005;23:5542) reported a mean objective remission rate (RR) of 32% with a median time to progression (TTP) of 24.6 weeks (wks) for 3-weekly docetaxel 100mg/m², while the corresponding figures for paclitaxel 175mg/m² were 25% and 15.6wks respectively. Nevertheless, excessive toxicity, especially myelosuppression, precludes their use in frail and/or elderly patients (pts). For the latter, weekly schemes were developed, which proved tolerable without losing efficacy. This randomized phase II trial investigated the efficacy and the tolerability of weekly docetaxel or paclitaxel in MBC pts considered unfit for a 3-weekly therapy. Eligibility criteria were age >70 years, particular risk for myelosuppression (febrile neutropenia during previous chemotherapy, extensive radiation therapy, proven bone marrow invasion) or impaired hepatic function.
 Study design: 70pts accrued from Jan. 2002 to Aug. 2005 were randomized between arm A (33pts) receiving paclitaxel 80mg/m² weekly x8, and arm B (37pts), receiving docetaxel 36mg/m² weekly x8 after which a clinical response evaluation including CT-scan was performed. Pts with objective remission or stable disease (SD) pursued treatment 3/4 or 2/3 wks untill progression or unacceptable toxicity. For all pts, this was the first exposure to taxanes, unless they had received it in an adjuvant scheme, or in a palliative scheme with at least a 4 months lasting response. Study-endpoints were RR, TTP, overall survival (OS) and tolerability.
 Results: With paclitaxel, we obtained a RR of 55.2%, SD in 27.6% and progressive disease (PD) in 17.2% of the pts; median TTP was 21.1wks (95% CI:14.9-29.0) and median survival 55.7wks (95% CI:28.6-79.0). Corresponding results for docetaxel were: a RR of 45.2%, SD in 19.4% and PD in 35.4%; median TTP was 12.7wks (95% CI:8.4-29.3) and median survival 32wks (95% CI:19.4-50.9). Docetaxel and paclitaxel are known to have a different toxicity profile in 3-weekly regimens, with more hematotoxicity for docetaxel. In our study, boths products had a similar toxicity profile with more anemia, neutropenia and febrile neutropenia in the paclitaxel arm.
 Conclusions: Our study demonstrates that in pts with MBC unfit for 3-weekly docetaxel or paclitaxel, weekly administration of either compound may certainly be considered after anthracycline failure. They display different, but acceptable toxicity profiles, with levels of antitumoral efficacy comparable to those previously reported for 3-weekly regimens. A true valid comparison would require extension into a phase III trial. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6115.