flexible dosing of capecitabine,docetaxel does not compromise efficacy
If GI symptoms or hand-foot syndrome symptoms are limiting the tolerability of the combination, it appears fine to alter one or both doses as needed. Hope this is good news for someone this weekend!
20 September 2006
Capecitabine/docetaxel flexible dosing 'a reasonable strategy'
The tolerability of capecitabine plus docetaxel can be improved by reducing the starting dose of one or both agents, a detailed analysis has shown.
An international team headed by Robert Leonard (Southwest Wales Cancer Institute, Swansea, UK) retrospectively analyzed data from a phase III clinical trial in women with metastatic breast cancer. The study compared 3-weekly capecitabine (1250 mg/m² twice daily days 1–14) plus docetaxel (75 mg/m²2 day 1) with 3-weekly docetaxel (100 mg/m²2 day 1).
The main findings of the study, originally published in 2002, showed that the combination strategy was significantly superior to docetaxel monotherapy but increased severe side effects, including gastrointestinal adverse events and hand-foot syndrome.
In the present analysis, Leonard et al identified participants in the combination arm who were unable to tolerate the full dosages. The majority of these patients had capecitabine and docetaxel simultaneously reduced to 950 mg/m²2 and 55 mg/m²2, respectively.
Following dose-reduction, the proportion of treatment cycles with grade 3/4 adverse events was 17%, compared with 34% in the rest of the cohort who remained on full-dose.
Importantly, time to progression and overall survival were similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles.
Leonard's group says that this analysis, together with several phase II studies of taxanes with reduced-dose capecitabine, indicates that capecitabine/docetaxel dosing flexibility allows side effects to be managed without compromising efficacy.
"Reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer," they conclude. "In addition, reducing the dose of both agents may be appropriate."
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