Optimizing treatment sequencing of chemotherapy for patients with rectal cancer: The KIR randomized phase II trial

• Published in: Radiotherapy and oncology Vol. 155; pp. 237 - 245
• Main Authors: Garant, Aurelie, Kavan, Petr, Martin, André-Guy, Azoulay, Laurent, Vendrely, Véronique, Lavoie, Caroline, Vasilevsky, Carol-Ann, Boutros, Marylise, Faria, Julio, Nguyen, Trung Nghia, Ferland, Emery, Des Groseilliers, Sylvain, Cloutier, Alexis-Simon, Diec, Hugo, Drolet, Sébastien, Richard, Carole, Batist, Gerald, Vuong, Té
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01-02-2021
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Brachytherapy; Chemotherapy, Adjuvant; Colorectal neoplasms; Disease-Free Survival; Fluorouracil - therapeutic use; Humans; Induction chemotherapy trial; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Oxaliplatin; Rectal Neoplasms - pathology; Rectum cancer; Induction chemotherapy trial; Brachytherapy; Oxaliplatin; Rectum cancer; Colorectal neoplasms
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2020.11.008

•This randomized trial explores induction oxaliplatin-based chemotherapy for rectal cancer.•It prospectively confirms improved compliance of oxaliplatin-based induction chemotherapy.•Outcomes appear highly favorable despite limited patient radiation exposure.
Randomized studies have shown low compliance to adjuvant chemotherapy in rectal cancer patients receiving preoperative chemotherapy and external beam radiation (CT/EBRT) with total mesorectal excision. We hypothesize that giving neoadjuvant CT before local treatment would improve CT compliance.
Between 2010–2017, 180 patients were randomized (2:1) to either Arm A (AA) with FOLFOX x6 cycles prior to high dose rate brachytherapy (HDRBT) and surgery plus adjuvant FOLFOX x6 cycles, or Arm B (AB), with neoadjuvant HDRBT with surgery and adjuvant FOLFOX x12 cycles. The primary endpoint was CT compliance to ≥85% of full-dose CT for the first six cycles. Secondary endpoints were ypT0N0, five-year disease free survival (DFS), local control and overall survival (OS).
Patients were randomized to either AA (n = 120, median age (MA) 62 years) or AB (n = 60, MA 63 years). 175/180 patients completed HDRBT as planned (97.2%). In AA, two patients expired during CT; three patients post-randomization received short course EBRT because of progression under CT (n = 2, AA) or personal preference (n = 1, AB). ypT0N0 was 31% in AA and 28% in AB (p = 0.7). CT Compliance was 80% in AA and 53% in AB (p = 0.0002). Acute G3/G4 toxicity was 35.8% in AA and 27.6% in AB (p = 0.23). With a median follow-up of 48.5 months (IQR 33–72), the five-year DFS was 72.3% with AA and 68.3% with AB (p = 0.74), the five-year OS 83.8% for AA and 82.2% for AB (p = 0.53), and the five-year local recurrence was 6.3% for AA and 5.8% for AB (p = 0.71).
We confirmed improved compliance to neoadjuvant CT in this study. Although there is no statistical difference in ypT0N0 rate, local recurrence, and DFS between the two arms, a trend towards favourable oncological outcomes is observed.