The taxane agents have been used in breast cancer therapy for about a decade. Despite much clinical research, their most appropriate place amongst the numerous chemotherapy agents available remains arguable. JM Nabholtz (Edmonton, Canada) presented data on behalf of the TAX306 study group from a phase III trial comparing the combination of doxorubicin plus docetaxel (AT) versus the standard combination of doxorubicin plus cyclophosphamide (AC) as first line chemotherapy in patients with metastatic breast cancer. Although the data were preliminary, with a short overall median follow-up, the study showed that the AT combination had a significantly higher response rate (60 versus 47%, P = 0.008) as well as having fewer patients progressing whilst on treatment. However, this improved response rate was at a cost of increased neutropaenia (82 versus 69%), but cardiac toxicity was similar between the groups. Most interesting were the excellent response rates seen in patients with poor-prognostic disease. If more mature results indicate a significant survival benefit then the combination of a taxane with an anthracycline may become the new first-line standard of care in metastatic breast cancer.
In theory, liposome-encapsulated anthracyclines should have an improved therapeutic index, the active drug being released at the site of tumour. AT Chan (Hong Kong - on behalf of the TLC D-99 study group) presented data from a study comparing liposome-encapsulated doxorubicin (TLC D-99) plus cyclophosphamide versus epirubicin plus cyclophosphamide in the first-line treatment of metastatic breast cancer. The results showed that while response rates were similar (46 versus 39%), the patients receiving TLC had an improved progression free survival (PFS) of 7.7 versus 6.0 months (P = 0.04). There was however increased toxicity, especially stomatitis, in the TLC group. What impact this study will have on the further development and use of liposome-encapsulated anthracyclines is difficult to know. Although significant, the improvement in PFS is small. Comparisons of toxicity are difficult, as it has been clearly shown that at equimolar doses (as used in this study: 75 mg/m2), epirubicin is significantly less toxic than doxorubicin. Finally, a small study was presented by JA O'Hagan (Liverpool, UK) comparing capecitabine with paclitaxel in women with metastatic breast cancer failing previous anthracycline therapy. Capecitibine is a tumour selective oral fluoropyrimidine that is ultimately converted to 5-fluorouracil (5FU). Its great potential advantage is its oral route of administration. Results showed that capecitabine had comparable efficacy to paclitaxel but with an improved toxicity profile. Unfortunately, the numbers in the study (n= 42) preclude any meaningful conclusions. Nevertheless, further study of this agent is definitely warranted and is proceeding.