Phase II study of weekly intravenous oxaliplatin combined with oral daily capecitabine and radiotherapy with biologic correlates in neoadjuvant treatment of rectal adenocarcinoma.
OBJECTIVE
To evaluate the efficacy of a combination of capecitabine, oxaliplatin, and radiotherapy (RT) in the neoadjuvant treatment of Stage II and III rectal cancers.


METHODS
Capecitabine was given at 725 mg/m(2) orally twice daily Monday through Friday concurrently with RT. Oxaliplatin was given intravenously at 50 mg/m(2) once weekly five times starting the first day of RT. The radiation dose was 50.4 Gy in 28 fractions (1.8 Gy/fraction), five fractions weekly. Endorectal tumor biopsies were obtained before treatment and on the third day of treatment to explore the effects of treatment on thymidine phosphorylase, thymidylate synthase, excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1), and apoptosis.


RESULTS
A total of 25 patients were enrolled in this study; 6 patients (24%) had a complete pathologic response. T-downstaging occurred in 52% of patients, and N-downstaging occurred in 53%. Grade 3 diarrhea was the most common Grade 3-4 toxicity, occurring in 20% of patients. Only 2 patients experienced disease recurrence, with a median of 20 months of follow-up. Thymidylate synthase, thymidine phosphorylase, ERCC1, and apoptosis did not vary significantly between the pretreatment and Day 3 tumor biopsies, nor did they predict for T-downstaging or a complete pathologic response.


CONCLUSIONS
Capecitabine at 725 mg/m(2) orally twice daily, oxaliplatin 50 mg/m(2)/wk, and RT at 50.4 Gy is an effective neoadjuvant combination for Stage II and III rectal cancer and results in a greater rate of complete pathologic responses than historically shown in fluoropyrimidine plus RT controls.
Fakih
Marwan G
MG
Department of Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Bullarddunn
Kelli
K
Yang
Gary Y
GY
Pendyala
Lakshmi
L
Toth
Karoly
K
Andrews
Chris
C
Rustum
Youcef M
YM
Ross
Mary Ellen
ME
Levea
Charles
C
Puthillath
Ajithkumar
A
Park
Young-Mee
YM
Rajput
Ashwani
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D000069287:Capecitabine; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D004334:Drug Administration Schedule; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; C071447:ERCC1 protein, human; D004720:Endonucleases; D005472:Fluorouracil