Effect of PRM1201 Combined With Adjuvant Chemotherapy on Preventing Recurrence and Metastasis of Stage III Colon Cancer: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Ru Jia,Ling Zhao,Lihong Zhou,Yanbo Zhang,Guoxiang Cai,Huaimin Liu,Youying Lai,Yuanyuan Feng,Haijuan Xiao,Ningning Liu,Jiege Huo,Hui Liu,Qi Li,Xiaoqiang Yue,Puhua Zeng,Yan Wang,Xiaoting Sun,Hongjie Liu,Yi Zhang,Yun Zhang,Qing Ji,Huan Gong ,Chao Wu ,Zhigang Han ,Gang Hou

doi:10.3389/fonc.2021.618793

Abstract

BackgroundChemotherapy is the standard adjuvant treatment for colon cancer. Chinese herbal formula PRM1201 improves the efficacy of chemotherapy when used in combination with Cetuximab or Bevacizumab in patients with metastatic colorectal cancer. This study aims to explore the benefits of treatment with chemotherapy plus PRM1201 in the postoperative adjuvant setting.MethodsIn this parallel-group study, patients who had undergone curative resection for stage III colon cancer were randomly assigned to receive adjuvant chemotherapy (FOLFOX q2w for 6 months, or CapeOx q3w for 6 months) plus PRM1201 (chemo+PRM1201 group) or adjuvant chemotherapy plus placebo (chemo+placebo group). The primary endpoint was disease-free survival (DFS), and the secondary endpoints were quality of life (QOL) and toxicity.ResultsA total of 370 patients were randomly assigned to chemotherapy plus PRM1201 group (n = 184) and chemotherapy plus placebo group (n = 186). Up to October 30, 2019, 96 events of recurrence, metastasis, or death had been reported, of which 38 events were in the group of chemotherapy plus PRM1201 and 58 events in the chemo+placebo group. The 3-year DFS rate was 77.1 and 68.6% in the chemo+PRM1201 and chemo+placebo group, respectively (hazard ratio [HR], 0.63; 95% CI, 0.42 to 0.94). The QOL of patients in the chemo+PRM1201 group were significantly improved in terms of global quality of life, physical functioning, role functioning, emotional functioning, fatigue, and appetite loss. The incidence of grade 3 or 4 treatment-related adverse event (TRAEs) were similar between the two arms.ConclusionsChemotherapy in combination with PRM1201 improved the adjuvant treatment of colon cancer. PRM1201 can be recommended as an effective option in clinical practice.Clinical Trial RegistrationChinese Clinical Trials Registry, identifier ChiCTR-IOR-16007719.

Highlights

Colon cancer (CRC) is a common type of gastrointestinal tumor which has a high rate of fatality, ranking as the second leading cause of cancer-related death worldwide [1]
This was a randomized, double-blinded, placebo-controlled clinical trial conducted in seven tertiary hospitals in China, including: Shuguang Hospital, Shanghai University of Traditional Chinese Medicine; Fudan University Shanghai Cancer Center; Hospital Affiliated to Shaanxi University of Chinese Medicine; Hunan University of Chinese Medicine Integrated Chinese and Western Medicine Affiliated Hospital; Henan Cancer Hospital; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine; and Shanghai Changzheng Hospital
Oxaliplatin [19] and capecitabine [20] are the most commonly used chemotherapeutic drugs, and FOLFOX and CapeOx regimens are the first-line chemotherapy for stage III colon cancer according to the National Comprehensive Cancer Network (NCCN) guidelines

Summary

Introduction

Colon cancer (CRC) is a common type of gastrointestinal tumor which has a high rate of fatality, ranking as the second leading cause of cancer-related death worldwide [1]. After receiving standard treatments, such as surgery, and chemotherapy, recurrence and metastasis are still the most important factors related to the survival of patients [2]. The International Duration Evaluation of Adjuvant Therapy (IDEA) study showed that more than 25% of patients with stage III colon cancer had recurrence or metastasis within 3 years after surgery even with standard adjuvant chemotherapy [3]. In addition to surgery and chemotherapeutic drugs, most Chinese patients seek help from traditional Chinese medicine during or after standard first-line therapy. Few studies have focused on the effects of CHM treatment on survival outcomes in stage III colon cancer, and its use remains controversial. Chinese herbal formula PRM1201 improves the efficacy of chemotherapy when used in combination with Cetuximab or Bevacizumab in patients with metastatic colorectal cancer. This study aims to explore the benefits of treatment with chemotherapy plus PRM1201 in the postoperative adjuvant setting

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Conclusion