title: Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study.
abstract: PURPOSE The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance. PATIENTS AND METHODS A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A-preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR). Results On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period. CONCLUSION Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted.
authors.affiliation: Calle Profesor Beltran Báguena no 9.,Valencia, Spain 46009. cfmartos@fivo.org
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Martos
authors.forename: Carles
authors.initials: C
authors.lastname: Pericay
authors.forename: Jorge
authors.initials: J
authors.lastname: Aparicio
authors.forename: Antonieta
authors.initials: A
authors.lastname: Salud
authors.forename: Mariajose
authors.initials: M
authors.lastname: Safont
authors.forename: Bertomeu
authors.initials: B
authors.lastname: Massuti
authors.forename: Ruth
authors.initials: R
authors.lastname: Vera
authors.forename: Pilar
authors.initials: P
authors.lastname: Escudero
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
authors.forename: Eugenio
authors.initials: E
authors.lastname: Marcuello
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Mengual
authors.forename: Eugenio
authors.initials: E
authors.lastname: Saigi
authors.forename: Rafael
authors.initials: R
authors.lastname: Estevan
authors.forename: Moises
authors.initials: M
authors.lastname: Mira
authors.forename: Sonia
authors.initials: S
authors.lastname: Polo
authors.forename: Ana
authors.initials: A
authors.lastname: Hernandez
authors.forename: Manuel
authors.initials: M
authors.lastname: Gallen
authors.forename: Fernando
authors.initials: F
authors.lastname: Arias
authors.forename: Javier
authors.initials: J
authors.lastname: Serra
authors.forename: Vicente
authors.initials: V
authors.lastname: Alonso
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D013505:Digestive System Surgical Procedures; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000178:diet therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D018570:Risk Assessment; D013030:Spain / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil