Survival Benefit With Capecitabine/Docetaxel

SAN ANTONIO—Updated results from a major phase III study of docetaxel (Taxotere) plus capecitabine (Xeloda) in metastatic breast cancer confirmed the value of this new combination.

Joyce O’Shaughnessy, MD, co-director of breast cancer research at Baylor-Sammons Cancer Center and US Oncology, Dallas, presented the initial results at the 2000 San Antonio Breast Cancer symposium. Updated results were provided at the 2001 meeting by Sasha Vukelja, MD, of the Tyler Cancer Center, Tyler, Texas (abstract 352).

The study continues to show that docetaxel plus capecitabine yields a significant survival benefit, compared with docetaxel alone: Median survival of 14.5 months vs 11.5 months (P < .01), for a 22.5% reduced risk of death. Patients on the combination also had a significant difference in tumor response (32% vs 23%, P = .025) and longer median time to progression (6.1 months vs 4.2 months, P = .001).

The phase III study was a large international trial of 511 patients previously exposed to anthracyclines. Patients received either the combination of capecitabine 1,250 mg/m² twice daily on days 1 to 14 plus docetaxel 75 mg/m² on day 1 or monotherapy with docetaxel 100 mg/m² on day 1 of a 21-day cycle.

Based on these data, Dr. Vukelja said, "we believe an estimated additional 10% of patients with metastatic disease will be alive at the end of 12 months when on Xeloda/Taxotere combination chemotherapy, compared with Taxotere alone."

In addition, other investigators who conducted a poststudy analysis of the data (abstract 442) suggested that the survival advantage with the combination may be underestimated due to poststudy crossover in the single-agent arm. Twenty-eight percent of the 166 patients receiving poststudy chemotherapy received capecitabine, which was associated with improved outcomes, compared with other poststudy agents.

The choice of poststudy therapy was not defined in the protocol and was selected at the discretion of the investigator. After a minimum follow-up of 23 months, 218 patients (85%) in the combination arm and 198 patients (77%) in the docetaxel arm have received at least one poststudy treatment.

David Miles, MD, of Guy’s and St. Thomas’ Hospital, London, reported that patients receiving single-agent capecitabine poststudy had a 50% decreased risk of dying, compared with patients receiving other agents (P = .0046). Median survival was 21 months in patients receiving single-agent capecitabine vs 12.3 months in patients receiving any other chemotherapy agent.

"Until a randomized trial shows that the sequential administration of these agents achieves equivalent survival to the combination therapy, the docetaxel/capecitabine regimen should be considered the therapy of choice for patients with anthracycline-pretreated metastatic breast cancer," Dr. Miles said.

Dr. O’Shaughnessy commented, "I can count on just a couple of fingers the patients who don’t have a response to this combination. While there is some toxicity associated with it, it is very effective and it’s a great way to get good control of the disease and to provide symptom palliation. There are now at least five planned adjuvant trials also evaluating this combination."

Adverse Effects

Grade 3 toxicities occurred in 71% of the combination arm and 49% of the single-agent arm; grade 4 adverse events were less frequent with the combination regimen: 25% vs 31%, respectively. The doublet caused more gastrointestinal side effects and hand-foot syndrome than docetaxel alone, while patients receiving docetaxel alone had more neutropenic fever, myalgia, arthralgia, and pyrexia. The majority of treatment-related events in both arms were mild to moderate.

Dr. Vukelja said that she and her staff are very alert to the slightest indication of hand-foot syndrome, and treat it aggressively with lanolin creams and short treatment interruptions.

Cost-Effectiveness

Also at the San Antonio meeting, Dr. O’Shaughnessy reported a pharmacoeconomic analysis of the capecitabine/docetaxel combination (abstract 264).

Because the combination used a lower docetaxel dose than the monotherapy regimen, the total cost of the combination was only slightly higher: $21,024 vs $20,041 for monotherapy. "The acquisition cost of capecitabine was 93% offset by the lower docetaxel cost," she said.

Also, despite longer treatment duration for the combination, patients on the combination had fewer hospitalization days: 4.84 per patient vs 5.49 for docetaxel monotherapy.