Skip to main content

CLINICAL TRIAL article

Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1468279
This article is part of the Research Topic Recent Advances and New Challenges in Minimally Invasive Surgery and Chemotherapy for Colorectal Cancer-volume 2 View all articles

A Randomized Phase 3 Trial of Total Neoadjuvant Therapy (induction chemotherapy, neoadjuvant chemoradiation, neoadjuvant chemotherapy and surgery) vs Standard Long-term Chemoradiation Therapy (neoadjuvant chemoradiation, surgery and adjuvant chemotherapy) in Locally Advanced Rectal Cancer

Provisionally accepted
Freshte Foroughi Freshte Foroughi 1*Seyed Alireza Javadinia Seyed Alireza Javadinia 2*Roham Salek Roham Salek 1*
  • 1 Mashhad University of Medical Sciences, Mashhad, Razavi Khorasan, Iran
  • 2 Sabzevar University of Medical Sciences, Sabzawār, Iran

The final, formatted version of the article will be published soon.

    Purpose: We aimed to assess whether administering neoadjuvant chemotherapy before and after preoperative chemoradiotherapy could increase the pathological complete response rates. Methods: We did a phase 3, multicenter, randomized trial at four hospitals in Iran. Adult patients with a newly diagnosed, biopsy-proven, locally advanced non-metastatic rectal adenocarcinoma with an ECOG performance status of 0-2 were randomly assigned (2:2) to either the total neoadjuvant treatment (TNT) group or standard-of-care group, using a block randomized design. Investigators and participants were not masked to treatment allocation and treatment groups. The TNT group received neoadjuvant chemotherapy with FOLFOX6 (intravenous oxaliplatin 85 mg/m2 and leucovorin 400 mg/m2, followed by intravenous 400 mg/m2 fluorouracil bolus and then continuous infusion at a dose of 2400 mg/m2 over 46 h every 14 days for 4 cycles before and 4 cycles after chemoradiotherapy), chemoradiotherapy (50.4 Gy during 28 fractions and 800 mg/m2 concurrent oral capecitabine twice daily for 5 days per week), and total mesorectal excision. The standard-of-care group received neoadjuvant chemoradiotherapy, total mesorectal excision, and adjuvant chemotherapy (8 cycles). The primary endpoint was the pathological complete response (pCR). Safety analyses were done on treated patients. Results: Overall, 25 patients and 27 patients were enrolled in the TNT and the standard-of-care groups. Both groups were similar in term of gender, age, and tumor differentiation. Tumors in the standard-of-care group were significantly located closer to the anal verge comparing to TNT group (TNT: 9.4 ± 3.7 cm vs standard: 6.8 ± 4 cm, p=0.02). A pathologic complete response was reached in 48% (12/25) and 25.9% (7/27) of patients in the TNT group and the standard-of-care group, respectively (p=0.4). R0 resection rates was also identical between two groups (92% vs 88.9%, p=0.3). The toxicity rates were similar between two groups. Conclusion: Our results showed that TNT is a safe and feasible treatment approach in patients with rectal cancer and it may improve the overall pCR rate compared with standard treatment.

    Keywords: rectal cancer, Total neoadjuvant therapy, Neoadjuvant chemotherapy, Adjuvant chemotherapy, Neoadjuvant chemoradiotherapy, randomized controlled trial

    Received: 21 Jul 2024; Accepted: 31 Oct 2024.

    Copyright: © 2024 Foroughi, Javadinia and Salek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Freshte Foroughi, Mashhad University of Medical Sciences, Mashhad, 91778 9919, Razavi Khorasan, Iran
    Seyed Alireza Javadinia, Sabzevar University of Medical Sciences, Sabzawār, Iran
    Roham Salek, Mashhad University of Medical Sciences, Mashhad, 91778 9919, Razavi Khorasan, Iran

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.