Neoadjuvant FOLFOX Chemotherapy for Colon Cancer: Long-Term Chemotherapy-Induced Peripheral Neuropathy and Impact on Quality of Life (NEOCIPN-COLON)

February 19, 2025 updated by: Yulia Karagodina, P. Herzen Moscow Oncology Research Institute

Assessment of Long-Term Chemotherapy-Induced Peripheral Neuropathy and Its Impact on Quality of Life in Colon Cancer Patients After Neoadjuvant Platinum-Containing Chemotherapy

The goal of this observational study was to learn about the long-term effects of neoadjuvant (pre-surgery) chemotherapy on patients with locally advanced colon cancer. The main focus was to better understand the severity of long-lasting nerve damage, known as chemotherapy-induced peripheral neuropathy (CIPN), and its impact on patients' quality of life (QoL).

The key question the study aimed to answer was: What is the long-term severity of this common adverse event, and how much of an impact does it have on patients' quality of life?

Participants provided detailed responses about the severity of their CIPN symptoms and the overall impact on their well-being using the FACT-GOG-Ntx questionnaire.

Study Overview

Status

Completed

Conditions

Detailed Description

Introduction. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect experienced by many cancer patients receiving neurotoxic agents such as oxaliplatin. CIPN can manifest as numbness, tingling, and neuropathic pain, significantly impairing patients' quality of life (QoL). While the acute development of CIPN during chemotherapy treatment is well documented, the long-term persistence and severity of CIPN symptoms after completion of therapy is less understood.

The relatively new approach to treatment of patients with locally advanced colon cancer involves starting treatment with neoadjuvant (pre-operative) chemotherapy regimens containing oxaliplatin, such as FOLFOX, followed by definitive surgical resection and potentially additional adjuvant chemotherapy. This strategy has proven to be non-inferior to more established adjuvant (post-operative) chemotherapy, according to results of several clinical trials. However, the impact of this long-term CIPN on patient-reported outcomes and QoL in the setting of neoadjuvant chemotherapy has not been thoroughly investigated.

Additionally, there is interest in exploring whether modifying the sequence of neoadjuvant and adjuvant chemotherapy regimens could potentially mitigate the severity of CIPN. Specifically, a hypothesis can be made that delivering a reduced volume of oxaliplatin-containing chemotherapy (6 cycles of neoadjuvant FOLFOX) followed by a break for surgery, with only selective use of additional adjuvant chemotherapy based on response, may result in less cumulative neurotoxicity and improved long-term CIPN outcomes compared to the standard approach of administering the full course of chemotherapy after surgery.

The primary objective of this observational study was to characterize the long-term severity of CIPN symptoms and the associated impact on QoL in patients with locally advanced colon cancer who received neoadjuvant FOLFOX chemotherapy, followed by surgical resection and response-dependent adjuvant chemotherapy.

Study Design and Participants. This was a single-center, prospective observational study conducted at an academic medical center. Adult patients (≥18 years old) with histologically confirmed, locally advanced adenocarcinoma of the colon (clinical stage III or high-risk stage II) were eligible for enrollment. Key inclusion criteria included an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, adequate organ function, and no prior systemic chemotherapy or radiotherapy.

Eligible patients were enrolled and received 6 cycles of neoadjuvant FOLFOX chemotherapy. FOLFOX consisted of oxaliplatin 85 mg/m2 IV on day 1, leucovorin 400 mg/m2 IV on day 1, and 5-fluorouracil 400 mg/m2 IV bolus on day 1 followed by 2400 mg/m2 continuous IV infusion over 46 hours, every 2 weeks.

After completing six cycles of neoadjuvant FOLFOX chemotherapy, patients underwent definitive surgical resection of their primary tumor. For those who achieved a favorable pathologic response (defined as pT0-2N0M0 or pT3N0M0 without risk factors), no additional adjuvant chemotherapy was administered post-surgery. However, in cases of pT3N0M0 with the presence of risk factors, patients received 3 months of adjuvant capecitabine. Patients with a poor pathologic response were offered an additional six cycles of adjuvant FOLFOX chemotherapy.

Assessment of CIPN. Throughout the course of treatment, patients underwent clinical assessments for the development of CIPN. During treatment, a physician performed a neurological examination and graded the severity of CIPN using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. This standardized grading system classifies CIPN from grade 1 (mild) to grade 4 (life-threatening).

At a minimum of 3 months after the end of platinum-containing chemotherapy treatment, patients completed the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-Ntx) questionnaire. The FACT-GOG-Ntx is a validated, patient-reported outcome measure that evaluates the severity of CIPN symptoms and their impact on daily functioning and QoL.

The primary endpoint of this observational study was assessment of the long-term severity of CIPN and its impact on QoL, as measured by the FACT-GOG-Ntx questionnaire. The secondary target was assessment of correlation between various risk factors (older age (> 65 years), diabetes, Eastern Cooperative Oncology Group (ECOG) performance status, Body mass index (BMI) > 25, and higher cumulative oxaliplatin dose; cold temperatures during treatment) and severity of long-term CIPN.

Statistical Considerations. Descriptive statistics were used to summarize characteristics of patients. Associations between risk factors and ACIPN severity were evaluated using chi-squared tests. Two-tailed Mann-Whitney U tests were used to show significant differences in long-term CIPN outcomes and QoL scores between patient groups. Pearson and Spearman correlations were used to evaluate associations between risk factors and CIPN severity. Statistical significance was set at p < 0.05. Statistical analyses were performed using JASP (Version 0.18.3), an open-source statistical software package (JASP Team, 2024) or GraphPad Prism (GraphPad Software, San Diego, CA, USA).

Results. Between March 2021 and February 2024, a total of 54 patients were included and assessed by clinicians for acute CIPN during treatment. 45 of these patients provided complete FACT-GOG-Ntx questionnaire data for the long-term CIPN assessment, and 40 were included in the QoL analysis.

Study Type

Observational

Enrollment (Actual)

54

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Moscow, Russian Federation, 125284
        • P. Hertsen Moscow Oncology Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

This study includes patients who were treated for locally advanced colon cancer in P. Hertsen Oncology Clinical Research Institute in Moscow, Russian Federation

Description

Inclusion Criteria:

  • Patients with newly diagnosed, histologically confirmed, resectable colon cancer stage IIA - IIIC (cT3N0M0 [depth of invasion > 5 mm], cT4a-T4bN0M0, T1-4N1-2M0).
  • Age < 75 years.
  • ECOG performance status 0-1.
  • Hemoglobin > 9 g/dL.
  • Absolute neutrophil count > 1500/µL.
  • Platelet count > 100,000/µL.
  • Bilirubin level < 1.5 times the upper limit of normal.
  • Creatinine clearance > 60 mL/min (calculated using the Cockcroft-Gault formula).
  • ALT and AST levels < 2.5 times the upper limit of normal.

Exclusion Criteria:

  • Presence of distant metastases.

  • History of other oncological diseases, except for:

    1. Cured non-melanoma skin cancer without known signs of recurrence or progression for > 5 years.
    2. Cured carcinoma in situ without signs of recurrence or progression for > 5 years.
  • Clinically significant concomitant cardiac pathology (chronic heart failure NYHA class > 1; hypertension with a risk of cardiovascular complications > 3; history of myocardial infarction, stroke, or transient ischemic attack; presence of other decompensated cardiovascular diseases).
  • ECOG performance status > 1.
  • Presence of viral or infectious diseases (human immunodeficiency virus, chronic viral hepatitis, other infectious diseases in the acute phase).
  • History of clinically significant central nervous system disorders.
  • Clinically significant peripheral polyneuropathy (> grade 2).
  • Pregnancy or lactation.
  • Individual intolerance to the components of the treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Patients with colon cancer (II-III stage) who received neoadjuvant FOLFOX chemotherapy
54 Patients with locally advanced colon cancer who received platinum-containing chemotherapy as the initial phase of their treatment, followed by surgical resection and, if indicated, adjuvant chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of long-term chemotherapy-induced peripheral neuropathy
Time Frame: At least 3 months after the end of platinum-containing treatment
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity-13 Version 4 (FACT/GOG-Ntx) questionnaire. The FACT/GOG-Ntx total score ranges from 0-160 with higher scores indicating better QoL and/or fewer symptoms.
At least 3 months after the end of platinum-containing treatment
Patients' quality of life
Time Frame: At least 3 months after the end of platinum-containing treatment
Assessment using the the Functional Assessment of Cancer Therapy-General (FACT-G) scores within the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity-13 Version 4 (FACT/GOG-Ntx) questionnaire. The FACT-G score ranges from 0-108 with higher scores indicating better QoL and/or fewer symptoms.
At least 3 months after the end of platinum-containing treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Severity of acute chemotherapy-induced peripheral neuropathy
Time Frame: Through platinum-containing chemotherapy treatment completion, an average of 3,5 months
Assessed by physicians using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Grading criteria for peripheral sensory neuropathy was used (grade 1-4). Higher grade indicates worse symptoms.
Through platinum-containing chemotherapy treatment completion, an average of 3,5 months
Correlation between risk factors and severity of chemotherapy-induced peripheral neuropathy
Time Frame: Through study completion, an average of 2 years
Correlation between previously descriped risk factors (older age [> 65 years], diabetes, Eastern Cooperative Oncology Group [ECOG] performance status, Body mass index [BMI] > 25 and higher cumulative oxaliplatin dose) and severity of acute and long-term chemotherapy-induced peripheral neuropathy severity
Through study completion, an average of 2 years
Correlation between severity of long-term chemotherapy induced neuropathy and quality of life
Time Frame: At least 3 months after the end of platinum-containing treatment
Correlation between severity of long-term chemotherapy-induced peripheral neuropathy and patients' quality of life, as assessed by Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity-13 Version 4 (FACT/GOG-Ntx) questionnaire. FACT/GOG-Ntx total score ranges from 0-160 with higher scores indicating better QoL and/or fewer symptoms.
At least 3 months after the end of platinum-containing treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

P. Herzen Moscow Oncology Research Institute

Collaborators

Jiaxing University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 19, 2021

Primary Completion (Actual)

May 20, 2024

Study Completion (Actual)

May 20, 2024

Study Registration Dates

First Submitted

February 7, 2025

First Submitted That Met QC Criteria

February 19, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 19, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 72-2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Time Frame

Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis

IPD Sharing Access Criteria

Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan and execution of a Data Sharing Agreement

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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