ORLANDO—In a head-to-head comparison, two common regimens for metastatic breast cancer matched up, though the difference in toxicity profiles may give capecitabine (Xeloda) the edge over gemcitabine (Gemzar). The results “suggest that gemcitabine/docetaxel (Taxotere) followed by capecitabine at progression may be preferable,” said lead author Andrew Seidman, MD, of Memorial Sloan-Kettering Cancer Center, New York.
The study, conducted between February 2002 and December 2008, randomized 475 patients, 158 of whom crossed over to the opposite single agent at the same dose and schedule as in the combination. Patients received gemcitabine 1,000 mg/m2 on days one and eight plus docetaxel 75 mg/m2 on day 1, every three weeks (GD), with crossover at progression to capecitabine, or capecitabine 1,000 mg/m2 twice daily on days one to 14 plus docetaxel 75 mg/m2 (CD) on day one, every three weeks, with crossover to gemcitabine (ASCO 2009 abstract 1000).
GD and CD were associated with similar response rates, time to progression (TTP), and overall survival, Dr. Seidman reported, but more patients in the capecitabine arm discontinued therapy due to toxicity, and, in an exploratory analysis, more patients in the gemcitabine arm remained progression-free after crossover.
In previous studies, the addition of either gemcitabine or capecitabine to taxanes has yielded nearly identical efficacy, but more patients have discontinued capecitabine regimens, which has complicated prior phase III comparisons. In addition, few randomized trials have examined pre-planned crossover strategies, as the current trial did, Dr. Seidman said.
Time to progression was approximately nine months in each arm. GD was associated with significantly more grade 3-4 fatigue, hepatotoxicity, neutropenia, and thrombocytopenia, while CD was associated with significantly more grade 3-4 hand-foot syndrome, gastrointestinal toxicity, and mucositis. More patients in the CD arm discontinued treatment due to toxicity than those in the GD arm (28.4% vs 18.0%; P = .009), he reported.
In an exploratory analysis, time to progression from induction chemotherapy through crossover treatment was 14.3 months in the GD arm and 9.2 months in the CD arm (P = .09) for those 158 patients who indeed received the prespecified second-line single agent.
Putting the results into context, Dr. Seidman pointed out that the findings of longer summation TTP (first- and second-line therapy TTPs taken together for those patients who crossed over) suggested a benefit for the GD to C sequence over the CD to G sequence (five months gain in TTP through two lines of therapy). “We showed that the crossover populations were well-balanced for prognostic factors, and despite that only a third of patients crossed over, there were still more than 75 patients per arm,” he said.
Although the study results were positive, Daniel F. Hayes, MD, said that most patients do not need combination chemotherapy. Dr. Hayes is the Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Comprehensive Cancer Center in Ann Arbor.
“They will be equally well palliated by carefully applied, sequential single-agent therapy,” Dr Hayes told Oncology News International. “I don’t think most patients should be exposed to the toxicity of the two drugs at once.”