Gemcitabine/Docetaxel Comparable to Capecitabine/ Docetaxel in Metastatic Breast Cancer

August 1, 2005

NOTTINGHAM, UNITEDK I N G D O M - G e m c i t a b i n e(Gemzar)/docetaxel (Taxotere) andcapecitabine (Xeloda)/docetaxelshowed similar efficacy against metastaticbreast cancer, according to

NOTTINGHAM, UNITEDK I N G D O M - G e m c i t a b i n e(Gemzar)/docetaxel (Taxotere) andcapecitabine (Xeloda)/docetaxelshowed similar efficacy against metastaticbreast cancer, according toStephen Chan, DM, MRCP, of NottinghamCity Hospital in the UnitedKingdom (abstract 581).Although efficacy was similar, however,the toxicity profiles were different.Patients receiving gemcitabine/docetaxel had significantly fewer nonhematologictoxicities, includinghand-foot syndrome, mucositis, anddiarrhea. Fewer patients taking gemcitabinediscontinued the study dueto adverse events. Capecitabine-treatedpatients had significantly less hematologictoxicity.Dr. Chan reported the results of aEuropean phase III study comparingthe two regimens as first-line or second-line treatment for patients withanthracycline-pretreated metastaticbreast cancer. The median age was 56years for the gemcita-bine/docetaxelarm and 53 years for the capecitabine/docetaxel arm, and patients were wellbalanced for other characteristics.More than 60% of patients in each armhad liver metastases, and more than40% had lung metastases.

Patients were randomized to receivedocetaxel (75 mg/m2) on day 1and either gemcitabine (1,000 mg/m2)on days 1 and 8 or capecitabine (1,250mg/m2 twice daily) on days 1 to 14.Each cycle was 21 days long. The gemcitabinearm received more total cycles(875) than did the capecitabinearm (758), Dr. Chan reported. Therelative mean dose intensity was 73%for the gemcitabine arm vs 60% forthe capecitabine arm.Responses SimilarEfficacy data are based on 305 patientsrandomized and evaluable: 153in the gemcitabine group and 152 inthe capecitabine group (Table 1). Medianprogression-free survival, whichwas the primary objective of the study,was 35 weeks for both treatmentgroups. Overall response rates were32% in both treatment arms (P =.9332). Time to treatment failure was19 weeks in the gemcitabine group vs18 weeks in the capecitabine group (P= .5056).Nonhematologic ToxicitiesSafety data were based on 302 patientswho were randomized and receivedtreatment. Grade 3/4 hematologictoxicities were similar, withneutropenia and leukopenia being themost common for both regimens. Fornonhematologic toxicities, however,although there were no incidences ofgrade 3/4 hand-foot syndrome in thegemcitabine group, there were 39 cases(26%) in the capecitabine group.Grade 3/4 diarrhea was also more pronouncedin the capecitabine group,occurring in 25 patients (17%) vs 11patients (7%) in the gemcitabinegroup. Mucositis was experienced by20 patients (13%) in the capecitabinegroup vs 6 patients (4%) in the gemcitabinegroup.More serious adverse events occurringin the capecitabine group led todrug-related discontinuation oftherapy in 42 patients (28%) in thecapecitabine group vs 20 patients(13%) in the gemcitabine group."Gemcitabine, capecitabine, anddocetaxel are all highly active agents inanthracycline-pretreated metastaticbreast cancer. We believed that acomparison of gemcitabine andcapecitabine, each combined withdocetaxel, would provide valuableinformation for clinicians in choosingan optimal treatment," Dr. Chan said.The principal investigator for the studywas Pierre Fumoleau, MD, of the CentreRene Gauducheau, nantes-SaintHerblain, Herblain, France.More Clinically AcceptableCapecitabine Dose TestedIn a discussion of Dr. Chan's presentation,Andrew D. Seidman, MD,of the Breast Cancer Medicine Serviceat Memorial Sloan-Kettering CancerCenter, acknowledged that the gemcitabine/docetaxel doublet was associatedwith less toxicity, whereas theregimens were "indistinguishable"with respect to efficacy.Dr. Seidman pointed out that thecapecitabine dose in this study is theestablished dose and the dose for whichefficacy has been demonstrated, but itis not well tolerated by many patients,and therefore dose reductions are oftennecessary."Perhaps the more relevant and robustquestion addressing the optimalapplication of these agents in metastaticbreast cancer" is asked in anongoing international trial, Dr.Seidman said, "where patients withcancer progressing on gemcitabine/docetaxel cross over to capecitabineand patients with progression oncapecitabine/docetaxel cross over togemcitabine. Of note, this trial incorporateswhat many clinicians feel is amore clinically acceptable 20% lowerdose of capecitabine as a componentof this doublet, as compared with theChan trial." The dose of capecitabinein this international trial is 2,000mg/m2 in divided doses on 14 of the 21days in the cycle.