Safety of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection: a randomized, multicenter, prospective, phase III IOCCRC trial (IOCCRC)

Zhang, Rong Xin; Lin, Jun; Lei, Jian; Chen, Gong; Li, Li Ren; Lü, Zhen; Ding, Pei Rong; Jing, Huang; Kong, Ling Heng; Wang, Fu Long; Liu, Cong; Wu, Jiang; Ke, Chuan Feng; Zhou, Wei; Fan, Wen; Liu, Qing; Wan, De Sen; Wu, Xiao; Pan, Zhi Zhong

doi:10.1007/s00432-017-2489-0

Cited by 11 publications

(14 citation statements)

References 27 publications

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“…However, we observed that only 18% of our patients received this therapy, which might be a result of poor economic conditions and fear of side effects. Intraoperative chemotherapy has been gradually performed in rectal cancer patients in recent years, aimed at decreasing the rate of local recurrence and distant metastasis [25]. It is generally indicated for patients with T3/T4 or N+ rectal cancer.…”

Section: Gastroenterology Research and Practicementioning

confidence: 99%

A Retrospective Study of Risk Factors for Symptomatic Anastomotic Leakage after Laparoscopic Anterior Resection of the Rectal Cancer without a Diverting Stoma

Wang

Liu

2020

Gastroenterology Research and Practice

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Background. Anastomotic leakage (AL) is a common and devastating postoperative issue for patients who have undergone anterior resection of rectal carcinoma and can lead to increased short-term morbidity and mortality. Moreover, it might be associated with a worse oncological prognosis of tumors. This study is aimed at exploring the risk factors for symptomatic AL after laparoscopic anterior resection (LAR) for rectal tumors without a preventive diverting stoma. Materials and Methods. This case control study retrospectively reviewed the data of 496 consecutive patients who underwent LAR of the rectum without a preventive diverting stoma at the Cancer Hospital, Chinese Academy of Medical Sciences between September 2016 and September 2017. All patients were divided into an AL group and a control group based on the occurrence of postoperative symptomatic AL. Factors regarding patient-related variables, operation-related variables, and tumor-related variables were collected and assessed between the two groups through univariate and multivariate logistic regression analyses to identify independent risk factors for AL. Results. In total, 18 (3.6%) patients developed postoperative symptomatic AL. Univariate analysis showed that a synchronous primary malignancy of the left hemicolon (P=0.047), intraoperative chemotherapy (P=0.003), and level of anastomosis (P=0.033) were significantly related with AL. Multivariate analysis was subsequently performed to adjust for confounding biases and confirmed that a synchronous primary malignancy of the left hemicolon (odds ratio (OR), 12.225; 95% confidence interval (CI), 1.764-84.702; P=0.011), intraoperative chemotherapy (OR, 3.931; 95% CI, 1.334-11.583; P=0.013), and level of anastomosis (OR, 3.224; 95% CI, 1.124-9.249; P=0.030) were independent risk factors for symptomatic AL for patients who received LAR for rectal neoplasms without a preventive diverting stoma. Conclusions. Synchronous primary malignancy of the left hemicolon, intraoperative chemotherapy, and a low anastomotic level can increase the risks of postoperative symptomatic AL after LAR of the rectum without a protective diverting stoma.

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Section: Gastroenterology Research and Practicementioning

confidence: 99%

A Retrospective Study of Risk Factors for Symptomatic Anastomotic Leakage after Laparoscopic Anterior Resection of the Rectal Cancer without a Diverting Stoma

Wang

Liu

2020

Gastroenterology Research and Practice

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“…However, survival times was not evaluated. Safety of intraoperative chemotherapy with 5-FU for colorectal cancer patients was also performed 22, and showed that it can be safely performed during colorectal surgery. In our study, we used novel regimen of hydroxycamptothecin, tumor necrosis factor (TNF), 5-fluorouracil (5-FU), and calcium folinate (CF) for IOC, and follow up study indicated a prognostic benefit.…”

Section: Discussionmentioning

confidence: 99%

Intraoperative Chemotherapy with a Novel Regimen Improved the Therapeutic Outcomes of Colorectal Cancer

et al. 2019

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Background: This study sought to evaluate the efficacy of a novel intraoperative chemotherapy (IOC) regimen that consists of hydroxycamptothecin, tumor necrosis factor (TNF), 5-fluorouracil (5-FU), and calcium folinate (CF) on the outcomes of colorectal cancer (CRC). Methods: In total, 551 CRC patients who had undergone surgical resection were evaluated. Among these patients, 247 were treated with postoperative adjuvant chemotherapy, and 193 were treated with intraoperative chemotherapy. Of the CRC patients who underwent chemotherapy, 52 were treated with both postoperative adjuvant chemotherapy and intraoperative chemotherapy. Patients' characteristics, including age, sex, stage, differentiation, lymph node metastasis, surgical-pathological staging, tumor location, tumor size, and relapse-free survival, were collected. Results: IOC for CRC therapy was associated with a more favorable survival prognosis (HR, 0.30, 95%CI, 0.19-0.48, P<0.001) independent of other clinical covariates. CRC patients treated with IOC survived longer than patients who were not treated with IOC did during surgery (P<0.0001, Kaplan-Meier log rank). Meanwhile, a Kaplan-Meier analysis demonstrated that individuals who received both IOC and POC survived longer than patients who received only POC: for stage II and stage III patients (P=0.0001, Kaplan-Meier log rank), stage II patients alone (P=0.02, Kaplan-Meier log rank), and stage III patients alone (P=0.046, Kaplan-Meier log rank). Conclusions: The therapeutic effects of colorectal cancer by intraoperative chemotherapy with a novel regimen were enhanced, which improved the prognosis of patients with CRC.

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“…This enzyme is necessary for DNA replication, cells survival and proliferation, and then administration of 5‐Fluorouracil (5‐FU) disrupts cancer cells division and induces cell deaths via thymineless death. Consequently, it is used broadly for treatment of various cancers, such as rectal, colorectal and breast cancers (Bendell et al, ; Cameron et al, ; Zhang, Lin, et al, ). Also, co‐treatment of non‐small lung cancer cells with 5‐FU and TRAIL induced cell death remarkably through, firstly, survivin down‐regulation, and secondly, DR5 up‐regulation (Wang, Yang, & Wu, ).…”

Section: Intracellular Anti‐apoptotic Proteins As Targeted Therapymentioning

confidence: 99%

Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL

Hassanzadeh

Hagh

Alivand

et al. 2018

Journal Cellular Physiology

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis in different types of cancer cells via activation of caspase cascade. TRAIL interacts with its cognate receptors that placed on cancer cells surface, including TRAIL-R1 (death receptor 4, DR4), TRAIL-R2 (death receptor 5, DR5), TRAIL-R3 (decoy receptor 1, DcR1), TRAIL-R4 (decoy receptor 2, DcR2), and osteoprotegerin (OPG). Despite high apoptosis-inducing ability of TRAIL, various cancerous cells gain resistance to TRAIL gradually, and consequently TRAIL potential for apoptosis stimulation in these cells diminishes intensely. According to diverse ranges of examinations, intracellular anti-apoptotic proteins, such as cellular-FLICE inhibitory protein (c-FLIP), apoptosis inhibitors (IAPs), myeloid cell leukemia sequence 1 (MCL-1), BCL-2, BCL-XL, and survivin play key role in cancer cells resistance to TRAIL. These proteins attenuate cancer cells sensitivity to TRAIL via various functions, importantly through caspase cascade suppression. The c-FLIP avoids from caspase 8 activation by FADD via binding to caspase 8 cleavage of FADD. Moreover, it activates signaling pathways that involved in cancer cells survival and proliferation. Intriguingly, it appears that the down-regulation of intracellular anti-apoptotic proteins, particularly c-FLIP is effectiveness goal for TRAIL-resistant cancers therapy, because their up-regulation in association with poor prognosis has been observed in various types of TRAIL-resistant cancers. In this review, we tried to collect and examine investigations that researchers have been able to sensitize cancer cells to TRAIL through targeting of c-FLIP alone or with other intracellular anti-apoptotic proteins directly or indirectly. It seems that co-treatment of resistant cells by TRAIL with other therapeutic agents with the aim of intracellular anti-apoptotic proteins inhibition is hopeful and attractive approach to overcome various TRAIL-resistant cancers.

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Safety of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection: a randomized, multicenter, prospective, phase III IOCCRC trial (IOCCRC)

Abstract: Intraoperative chemotherapy can be safely performed during colorectal surgery; however, follow-up is necessary for a better assessment of its efficacy. ClinicalTrial.gov Register Number: NCT01465451.

Cited by 11 publications

References 27 publications

A Retrospective Study of Risk Factors for Symptomatic Anastomotic Leakage after Laparoscopic Anterior Resection of the Rectal Cancer without a Diverting Stoma

A Retrospective Study of Risk Factors for Symptomatic Anastomotic Leakage after Laparoscopic Anterior Resection of the Rectal Cancer without a Diverting Stoma

Intraoperative Chemotherapy with a Novel Regimen Improved the Therapeutic Outcomes of Colorectal Cancer

Down‐regulation of intracellular anti‐apoptotic proteins, particularly c‐FLIP by therapeutic agents; the novel view to overcome resistance to TRAIL

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