Randomized phase II study comparing the efficacy and safety of SOX versus mFOLFOX6 as neoadjuvant chemotherapy without radiotherapy for locally advanced rectal cancer (KSCC1301).

Abstract

BACKGROUND:

Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT.

METHODS:

Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.

RESULTS:

From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9-83.6) and 73.4% (95% CI 58.7-83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414-1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable.

CONCLUSION:

We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.

TRIAL REGISTRATION:

Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J.

• Authors: Keisuke Miwa, Eiji Oki, Masanobu Enomoto, Keisuke Ihara, Koji Ando, Fumihiko Fujita, Masahiro Tominaga, Shinichiro Mori, Goro Nakayama, Mototsugu Shimokawa, Hiroshi Saeki, Hideo Baba, Masaki Mori, Yoshito Akagi
• Journal: BMC cancer (BMC Cancer) Vol. 21 Issue 1 Pg. 23 (Jan 05 2021) ISSN: 1471-2407 [Electronic] England
• PMID: 33402130 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Drug Combinations
• Oxaliplatin
• S 1 (combination)
• Tegafur
• Oxonic Acid
• Leucovorin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, pathology)
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemotherapy, Adjuvant (mortality)
• Drug Combinations
• Female
• Fluorouracil (administration & dosage)
• Follow-Up Studies
• Humans
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Neoadjuvant Therapy (mortality)
• Oxaliplatin (administration & dosage)
• Oxonic Acid (administration & dosage)
• Prognosis
• Rectal Neoplasms (drug therapy, pathology)
• Survival Rate
• Tegafur (administration & dosage)