High Clinical Response Rate Achieved With Capecitabine/Radiotherapy in Locally Advanced Rectal Cancer

August 1, 2003

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.

HALLE, Germany-Oral capecitabine(Xeloda) plus radiation is a highlyeffective and well-tolerated neoadjuvanttreatment for locally advanced rectalcancer.The results of an interim analysis of aGerman multicenter, phase II study werereported by Juergen Dunst, MD, of Martin-Luther-Universitat Halle-Wittenberg,Halle, Germany (ASCO abstract 1113).In describing the basis for the phase IIstudy, Dr. Dunst explained, "As shown inour previous phase I dose-finding study(J Clin Oncol 20:3983-3991, 2002), theconcurrent administration of dailycapecitabine with radiotherapy appearsto be feasible and effective in advancedrectal cancer. The specific rationale forthis combination is based on experimentalfindings that thymidine phosphorylase,necessary for the final conversion ofcapecitabine and predominantly presentin tumor cells, is upregulated by radiotherapyin malignant but not in healthytissue."Study Objective"The objective of the present expandedphase II trial is to establish the use ofthis combined modality approach in amulticenter setting, focusing on its applicationas neoadjuvant treatment of cT3,cT4, fixed or primarily inoperable tumors,"Dr. Dunst continued."Oral capecitabine simplifies chemoradiationby avoiding the need for timeconsumingand complicated IV infusions,"Dr. Dunst noted. "Capecitabine isa highly effective, first-line treatment formetastatic colorectal cancer, and it has animproved safety profile compared withIV fluorouracil/leucovorin in both themetastatic and adjuvant settings."Capecitabine/RadiotherapyA total irradiation dose of 50.4 to 55.8Gy was administered in conventional dailydoses of 1.8 Gy over a period of approximately6 weeks. Capecitabine was givenat an oral dosage of 825 mg/m2 bid on eachday of the radiotherapy period, includingthe weekends, with the first daily dosegiven 2 hours before irradiation.So far, 46 patients (60% male, 40%female) have been recruited from six universityclinics in Germany since June 2001.The mean age was 65 years, with an EasternCooperative Oncology Group performancestatus of 0 or 1. Clinical stagingrevealed T3 tumors (48%) and T4 tumors(52%), and involved lymph nodes (cN+)in 53%.Data from 25 patients were availablefor the interim analysis. "Capecitabine/radiotherapy achieved a high clinical response rate," Dr. Dunst reported. "Therewas a clinical complete response or partialresponse in 72% of patients. Only 12%experienced disease progression duringneoadjuvant treatment. The high clinicalresponse rate with capecitabine/radiotherapywas accompanied by a high rate of R0resections and tumor downstaging."Dr. Dunst reported that the comparisonof initial diagnosis and pathologicfindings showed downstaging in 72% ofpatients, mainly from cT4 to pT3 to pT0.Only 8% of patients remained inoperableat the end of the irradiation period.Oral capecitabine was well-toleratedin combination with radiotherapy. Themost commonly reported adverse eventswere diarrhea, local erythema, neurologicpain, and nausea. The only grade 3 adverseevents were diarrhea in two patientsand local erythema in one patient. Therewere no grade 4 adverse events. "Oralcapecitabine/radiotherapy demonstrateda favorable and predictable safety profile,"Dr. Dunst said. "The majority ofadverse events were mild to moderate inintensity and there were no grade 4 adverseevents or laboratory abnormalities."Summarizing the interim results, Dr.Dunst said, "Oral capecitabine/radiotherapyachieved clinical responses in 72% ofpatients, enabling R0 resections in 89% ofpatients undergoing surgery. Seventy-ninepercent of patients undergoing resectionexperienced pathologically confirmed tumordownstaging. Oral capecitabine simplifieschemoradiation, avoiding the problemsand inconvenience associated withIV fluorouracil."