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Options Expanding With First-line Capecitabine (Xeloda) Combinations in Metastatic Breast Cancer: Presented at IBCEF

By Chris Berrie

VIENNA, AUSTRIA -- February 22, 2006 -- Capecitabine (Xeloda(R)) is one of the essential components of first-line treatment for patients with metastatic breast cancer (MBC), it is a highly effective oral agent, it extends overall survival, it has a favourable safety profile with minimal myelosuppression, even in combination with other agents, according to an overview presented here at the International Breast Cancer Expert Forum: Milestones in Management, Confidence and Care (IBCEF).

Arlene Chan, MD, Consultant Medical Oncologist, Mount Hospital, Perth, Australia, started her overview by illustrating the options for early treatment with capecitabine alone or in combination therapies. These specifically involve capecitabine monotherapy, capecitabine/docetaxel (XT) and capecitabine/paclitaxel (XP).

The potential benefits of the XT combination were first seen as a preclinical synergy in MX-1 breast cancer xenographs, where there was a significant (P < .05) reduction in tumour volume with XT versus docetaxel or capecitabine monotherapy. This was later shown to translate into a significant overall survival benefit with XT (n = 255) over docetaxel alone (n = 255) of 14.5 months versus 11.5 months, respectively (hazard ratio [HR], 0.77; P = .013). Dr. Chan noted that this survival benefit was maintained in a subanalysis of patients with aggressive disease.

She also described a more recent direct comparison of concurrent (XT) and sequential (T followed by X) docetaxel and capecitabine that was carried out with a cohort of patients with relatively poor prognosis metastatic breast cancer. The primary endpoint of response rate (RR) demonstrated concurrent XT (n = 50; RR, 68%) to be significantly more active than sequential therapy (n = 50; RR, 40%; P = .004). There was also improvement in overall survival (HR, 0.528, 95% confidence interval [CI], 0.283-0.811; P = .006), and was accompanied by an acceptable safety profile of concurrent versus sequential treatment.

Of particular interest, Dr. Chan said, is that an XT dose reduction from 1250/75 mg/m² to 1000/60 mg/m² resulted in a minimal decrease in overall survival (15.0 vs. 14.6 months, respectively). Therefore, this dose reduction did not compromise the efficacy of XT, but reduced the incidence of grade III/IV toxicity.

Consistent activity has been seen with the XP combination in patients with metastatic disease. Response rates with mixed paclitaxel regimens three times weekly varying from 40% to 73% across a range of trials. Again, this has been accompanied by a favourable safety profile for XP with three times weekly paclitaxel, with a low incidence of grade III/IV adverse events.

Capecitabine is therefore emerging as an important component in combination therapy, Dr. Chan said, and detailed other first-line combinations. One such is capecitabine/vinorelbine (XN), which has been tested as either first- or second-line treatment over a range of trials of metastatic breast cancer. The overall RR range was 40% to 68%, which demonstrates the consistently high activity obtained with XN, with low incidence of grade III/IV adverse events.

The final group of capecitabine first-line combinations Dr. Chan described related to capecitabine as an important addition to biological therapies. The first of these was from a recent trial that combined capecitabine with trastuzumab (Herceptin(R), XH) as first-line therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic disease. This trial saw an overall RR of 73% (n = 41) and a safety profile that included no grade IV adverse events or cardiac toxicity.

Similarly, in two further recent trials of XH that enrolled patients with pretreated HER2-positive disease, RRs of 41% and 52% were obtained, and no significant additional toxicity was observed with the addition of trastuzumab to capecitabine monotherapy.

Dr. Chan also discussed results seen with the combination of capecitabine with bevacizumab (Avastin(R), XA) in patients with heavily pretreated metastatic disease. In this trial, the 19% RR for capecitabine alone (n = 215) was significantly improved with XA (n = 229; RR, 30%; P = .008), and the only added toxicity was a case of grade III/IV hypertension.

Finally, Dr. Chan indicated that this XA combination and variations upon it are being further examined in a number of ongoing trials, in both late advanced breast cancer and first-line metastatic breast cancer settings.

She concluded that capecitabine has emerged as one of the essential components of first-line treatment for patients with metastatic breast cancer.

This conference was sponsored by Roche.


[Presentation title: X-panding Options With First-line Xeloda Combinations.]

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