Neoadjuvant capecitabine combined with standard radiotherapy in patients with locally advanced rectal cancer: mature results of a phase II trial.
OBJECTIVE
The objective of this expanded phase II trial was to confirm the safety results of the preceding phase I study and establish the efficacy of neoadjuvant radiochemotherapy with capecitabine in rectal cancer in a multicenter setting.


METHODS
96 patients (63% male, age 34-81 years) with advanced rectal cancer (cT3-4 or cN+) from seven university centers in Germany were recruited. All were to receive a total irradiation dose of 50.4-55.8 Gy with conventional fractions. Capecitabine was given at an oral dosage of 825 mg/m(2)bid on each day of the radiotherapy period with the first daily dose applied 2 h before irradiation, followed by surgery 6 weeks later.


RESULTS
Most of the patients suffered from an advanced primary tumor (cT3: 57%, cT4: 40%) with lymph node involvement in 60%. After neoadjuvant treatment, with a mean of 99% of the scheduled radiation dose actually delivered, a clinical response rate of 68% (95% confidence interval: 57-78%) was observed. Out of 87 evaluable patients undergoing surgery, a sphincter-preserving procedure could be performed in 51% and R0 resection in 94%. A pathologically complete response was achieved in six patients (7%, 95% confidence interval: 3-14%). The comparison of initial diagnosis and pathologic findings showed a downstaging in 61%. Acute toxicity with > 5% incidence of NCI (National Cancer Institute) grade >/= 3 included lymphopenia (12%), leukopenia (6%), and diarrhea (7%). Mild to moderate hand-foot syndrome occurred in 12% only. After a median follow-up of 48 months, the 5-year overall survival and tumor control data were, with regard to patient selection, in the expected range with an overall survival of 65%, a relapse-free survival of 47%, and a local recurrence rate after 5 years of 17%.


CONCLUSIONS
The data clearly confirm that capecitabine is an adequate substitute for 5-fluorouracil in preoperative chemoradiation of rectal cancer with a favorable safety profile.
Dunst
Juergen
J
Department of Radiotherapy, University of Lübeck, Lübeck, Germany. juergen.dunst@uk-sh.de
Debus
Juergen
J
Rudat
Volker
V
Wulf
Joern
J
Budach
Wilfried
W
Hoelscher
Tobias
T
Reese
Thomas
T
Mose
Stephan
S
Roedel
Claus
C
Zuehlke
Helmut
H
Hinke
Axel
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016737:Proctocolectomy, Restorative; D011880:Radiotherapy Planning, Computer-Assisted; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D012007:Rectum / Q000473:pathology / Q000601:surgery
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil