Complete Neoadjuvant Treatment for Rectal Cancer: The Brown University Oncology Group CONTRE Study.
OBJECTIVE
Following preoperative chemoradiation and surgery, many patients with stage II to III rectal cancer are unable to tolerate full-dose adjuvant chemotherapy. BrUOG R-224 was designed to assess the impact of COmplete Neoadjuvant Treatment for REctal cancer (CONTRE), primary chemotherapy followed by chemoradiation and surgery, on treatment delivery, toxicities, and pathologic response at surgery.


METHODS
Patients with clinical stage II to III (T3 to T4 and/or N1 to N2) rectal cancer received 8 cycles of modified FOLFOX6 followed by capecitabine 825 mg/m bid concurrent with 50.4 Gy intensity-modulated radiation therapy. Surgery was performed 6 to 10 weeks after chemoradiation.


RESULTS
Thirty-nine patients were enrolled between August 2010 and June 2013. Median age was 61 years (30 to 79 y); 7 patients (18%) were clinical stage II and 32 (82%) stage III. Thirty-six patients (92%) received all 8 cycles of mFOLFOX6, of whom 35 completed subsequent chemoradiation; thus 89% of patients received CONTRE as planned. No unexpected toxicities were reported. All patients had resolution of bleeding and improvement of obstructive symptoms, with no complications requiring surgical intervention. Pathologic complete response (ypT0N0) was demonstrated in 13 patients (33%; 95% CI, 18.24%-47.76%).


CONCLUSIONS
CONTRE seems to be a well-tolerated alternative to the current standard treatment sequence. Evaluating its impact on long-term outcomes would require a large randomized trial, but using pathologic response as an endpoint, it could serve as a platform for assessing the addition of novel agents to preoperative treatment in stage II to III rectal cancer.
Brown University Oncology Research Group, Providence, RI.
Kimberly
K
Perez
Howard
H
Safran
William
W
Sikov
Matthew
M
Vrees
Adam
A
Klipfel
Nishit
N
Shah
Steven
S
Schechter
Nicklas
N
Oldenburg
Victor
V
Pricolo
Kayla
K
Rosati
Thomas
T
Dipetrillo
D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine / Q000008:administration & dosage; D059248:Chemoradiotherapy / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D013505:Digestive System Surgical Procedures; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D060828:Induction Chemotherapy; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D050397:Radiotherapy, Intensity-Modulated; D012004:Rectal Neoplasms / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil