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

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.