Capecitabine/Taxane Sequential Therapy May Benefit Social Functioning More Than Capecitabine/Taxane Simultaneous Therapy

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Oncology NEWS InternationalOncology NEWS International Vol 12 No 8
Volume 12
Issue 8

This special supplement to Oncology News International includes 28 reportswith updated information on clinical trials investigating capecitabine and other agents inthe treatment of advanced colorectal and breast cancers, and other solid tumors.The reports summarize selected presentations from the 39th Annual Meeting of theAmerican Society of Clinical Oncology (ASCO) and related educational symposiaheld in conjunction with ASCO.

MEXICO CITY-In patientswith metastatic breast cancer, capecitabine(Xeloda) monotherapy followed bytaxane monotherapy offers greater benefitsin social functioning than capecitabine/taxane concurrent therapy. In somepatients, sequential therapy with capecitabineadministered before taxanes maytherefore be a more appropriate treatmentstrategy than capecitabine/docetaxel(Taxotere) or capecitabine/paclitaxelcombination therapy after anthracyclinefailure.These early results from a quality oflife (QOL) study conducted by the MexicanOncology Study Group were reportedby Laura Torrecillas, MD, medical oncologistand head of the chemotherapy serviceat the 20 Noviembre ISSSTE MedicalCenter in Mexico (ASCO abstract 3011).At the interim analysis, the phase III ongoingtrial shows a similar disease controlrate and a slightly inferior toxicity profilewith capecitabine alone followed by taxane,compared with the combination ofcapecitabine and docetaxel or paclitaxel.This study looked at whether sequentialmonotherapy could improve QOL morethan a first-line combined approach.Preliminary Data Focuson Capecitabine Monotherapy"In these preliminary data, few of thepatients in the sequential arm have receivedtaxane therapy, and therefore theresults are more representative of capecitabinemonotherapy than sequentialcapecitabine monotherapy followed atprogression by taxane monotherapy.However, mature results will provide aclearer indication of any differences betweenthese two treatment strategies" Dr.Torrecillas noted.In describing the rationale for the phaseIII study, the investigators pointed outthat capecitabine monotherapy has demonstratedconsistently high efficacy and afavorable safety profile in patients withmetastatic breast cancer who have beenpretreated either with anthracyclines orwith a combination of anthracyclines andtaxanes. Capecitabine is an oral, fluoropyrimidinecarbamate that generates fluorouracil(5-FU) preferentially in tumortissue through exploitation of high intratumoralconcentrations of thymidinephosphorylase (TP).The oral administration and good tolerabilityof capecitabine offer improvedpatient convenience, which would potentially enhance patient QOL. From oneperspective, the high single-agent activityof capecitabine, and the lack of overlappingtoxicity profiles with taxanes, in additionto their synergistic activity due toTP upregulation in tumor tissue, suggestthat they are most effectively administeredin combination.However, sequential therapy withcapecitabine administered as monotherapyfollowed by taxanes at disease progressionhas the potential to provide additionalQOL benefits compared withcombination therapy from the outset, assumingthat efficacy for cancer control issatisfactory.Three Treatment ArmsThe study compared three treatmentarms:

  • capecitabine monotherapy 1,250mg/m2 twice daily, days 1 to 14, followedby docetaxel or paclitaxel after progression(58 patients) vs
  • capecitabine/paclitaxel combinationtherapy, with capecitabine 825mg/m2 twice daily, days 1 to 14, plus paclitaxel175 mg/m2 day 1 (66 patients) vs
  • capecitabine/docetaxel combinationtherapy, with capecitabine 825mg/m2 twice daily, days 1 to 14 plus docetaxel75 mg/m2 day 1 (69 patients).

The treatment is continued until diseaseprogression or unacceptable toxicity.Side effects are managed by treatmentinterruption or dose reduction.The investigators report that the baselinecharacteristics were generally wellbalanced in the three groups. To be eligiblefor the study, patients were requiredto have measurable metastatic breast cancer,be between 18 and 75 years old, havea Karnofsky performance status ≥ 50, havea life expectancy greater than 3 months,and one prior anthracycline-based chemotherapyregimen. Prior adjuvant therapywith cyclophosphamide, methotrexate,fluorouracil (CMF) was alsopermitted. Patients could not have hadhormonal therapy less than 30 days priorto enrollment.

Questionnaire Assesses Trends

QOL was assessed using the EuropeanOrganization for Research and Treatmentof Cancer QLQ-C30 v2.0. The questionnaireis completed at baseline and at 3-week intervals (always before each treatmentcycle) until week 48, and at the endof the study.More than 80% of patients completedat least one QOL questionnaire after thestart of the study and were therefore evaluablefor the QOL outcome. Substantiallymore questionnaires were completed atthe end of the study in the capecitabine/docetaxel arm compared with the othertwo study arms.The global health status was similar inall three treatment arms. "No consistentor sustained trends have been observed inglobal health status during the study period,"Dr. Torrecillas reported. "At cycle eight, global health status is significantlyimproved with capecitabine/paclitaxelcompared with the other two arms, butthere are no significant differences betweentreatment arms at the end of thestudy."Social functioning was significantlyimproved with capecitabine monotherapyfollowed by taxane monotherapy comparedwith the other two study arms."This is possibly due to the oral administrationroute and favorable tolerability(including lack of hair loss) associatedwith taxane monotherapy," Dr. Torrecillasexplained."Further data are required to improvethe robustness of the results," Dr. Torrecillasnoted. "In addition, inclusion ofdata after administration of taxanetherapy in the sequential arm will providea more accurate representation of sequentialtherapy rather than the currentlyavailable data for the single-agentcapecitabine."

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