Improved Recurrence-Free Survival With Capecitabine, But Increased Adverse Events

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Main Category: Breast Cancer
Also Included In: Clinical Trials / Drug Trials;  Cancer / Oncology
Article Date: 10 Nov 2009 - 1:00 PST

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An article published Online First and in the December edition of The Lancet Oncology reports that addition of capecitabine to a standard chemotherapy regimen for breast cancer improves recurrence-free survival. On the other hand, treatment with capecitabine is frequently discontinued because of increased adverse events. The article is the work of Professor Heikki Joensuu, Helsinki University Central Hospital, Finland, and colleagues.

A total of 1,500 women with moderate-to-high risk early breast cancer participated in this randomized controlled trial. They were assigned to either three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine (capecitabine group, n=753), or to three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil (control group, n=747). The control combination was representative of a regimen frequently used in Finland and Sweden, and comparable to the regimen administered in many other countries. The primary endpoint was recurrence-free survival. The authors of this study carried out a planned interim analysis after three years of median follow-up.

Researchers established that recurrence-free survival at three years was better with the capecitabine regimen than with control (93 percent compared to 89 percent).The capecitabine regimen was associated with more cases of grade 3 or 4 diarrhoea (6 percent compared to 3 percent) and hand-foot syndrome(11 percent compared to less than 1 percent). Hand-foot syndrome is a swelling and numbness of the hands and feet that occurs with certain types of chemotherapy. The control regimen had more occurrences of grade 3 or 4 neutropenia (98 percent compared to 86 percent) and febrile neutropenia (9 percent compared to 4 percent). Neutropenia is an abnormally low number of neutrophils which are the most important type of white blood cell in the blood. Febrile neutropenia is associated fever, often with other signs of infection. More patients discontinued planned treatment in the capecitabine group (24 percent compared to 3 percent in the control arm).

The authors explain: "The capecitabine-containing chemotherapy regimen reduced breast cancer recurrence compared with a control schedule of standard agents. Capecitabine administration was frequently discontinued because of adverse effects... Our results suggest that integration of capecitabine upfront with potentially synergistic chemotherapeutic agents and into several cycles might be an effective treatment strategy."

They observe: "Integration of capecitabine was associated with frequent discontinuation of planned chemotherapy, but most patients could tolerate all six scheduled cycles. Studies that focus on further refinement of the current chemotherapy regimen are warranted."

In an associated comment, Dr Ruth M. O'Regan, Emory Winship Cancer Institute, Atlanta, GA, USA, remarks: "Although the findings of this trial are not practice-changing, they are intriguing and could merit further assessment in a larger trial. However, the significant toxicity noted with the addition of capecitabine to the taxane - anthracycline backbone dampens enthusiasm for further studies of this approach. More importantly, it is imperative that we take a more rational approach to the treatment of early-stage breast cancer by tailoring our treatment approaches to molecular phenotypes."

"Adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for breast cancer: an open-label, randomised controlled trial"
Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Riikka Huovinen, Arja Jukkola-Vuorinen, Minna Tanner, Raija Asola, Riitta Kokko, Johan Ahlgren, Päivi Auvinen, Akseli Hemminki, Outi Paija, Leena Helle, Lauri Nuortio, Kenneth Villman, Greger Nilsson, Sirpa-Liisa Lahtela, Kaisa Lehtiö, Marjo Pajunen, Paula Poikonen, Paul Nyandoto, Vesa Kataja, Petri Bono, Mika Leinonen, Henrik Lindman, on behalf of the FinXX Study Investigators
DOI: 10.1016/S1470-2045(09)70307-9
The Lancet Oncology

Written by Stephanie Brunner (B.A.)
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