Long-Term Prevalence of Sensory Chemotherapy-Induced Peripheral Neuropathy for 5 Years after Adjuvant FOLFOX Chemotherapy to Treat Colorectal Cancer: A Multicenter Cross-Sectional Study

Abstract

(1) Background: Oxaliplatin is among the most neurotoxic anticancer drugs. Little data are available on the long-term prevalence and consequences of chemotherapy-induced peripheral neuropathy (CIPN), even though the third largest population of cancer survivors is made up of survivors of colorectal cancer. (2) Methods: A multicenter, cross-sectional study was conducted in 16 French centers to assess the prevalence of CIPN, as well as its consequences (neuropathic pain, anxiety, depression, and quality of life) in cancer survivors during the 5 years after the end of adjuvant oxaliplatin chemotherapy. (3) Results: Out of 406 patients, the prevalence of CIPN was 31.3% (95% confidence interval: 26.8–36.0). Little improvement in CIPN was found over the 5 years, and 36.5% of patients with CIPN also had neuropathic pain. CIPN was associated with anxiety, depression, and deterioration of quality of life. None of the patients with CIPN were treated with duloxetine (recommendation from American Society of Clinical Oncology), and only 3.2%, 1.6%, and 1.6% were treated with pregabalin, gabapentin, and amitriptyline, respectively. (4) Conclusions: Five years after the end of chemotherapy, a quarter of patients suffered from CIPN. The present study showed marked psychological distress and uncovered a failure in management in these patients.

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms

“…Cold-induced neuropathy represents the most important difference between oxaliplatin and cisplatin-induced neuropathy [ 66 ] and its severity in the first phases of exposition has been associated to the chronic form of OIPN experienced one year later [ 67 ], observed in 50–70% of patients, depending on the intensity of symptoms assessed in its acute clinical presentation [ 68 , 69 , 70 ]. A systematic review by Beijers et al [ 71 ], in addition to the study by Briani et al has reported that OIPN may be present in 26–46% of patients at the 12-month follow-up, in 24% of patients at the 15–18-month follow-up and even in 84% of patients at the 24-month follow-up [ 71 , 72 , 73 ].…”

Flavonoids Alleviate Peripheral Neuropathy Induced by Anticancer Drugs

“…Unfortunately, recent in vivo and in vitro studies on CIPN states have yielded no major pharmacological advancements. Moreover, the majority of patients with CIPN receive no medical treatment for their symptoms [ 16 ]. These factors underscore the need for standardized, reliable treatments to improve cancer patients’ quality of life.…”

“…Oxaliplatin, paclitaxel, and bortezomib destabilize the nociceptor membrane by elevating the resting membrane potential toward the threshold; this increases the likelihood of an action potential. Oxaliplatin activates ion channels involved in action potential initiation and propagation [ 10 , 16 ]. Paclitaxel and bortezomib enhance the release of proinflammatory cytokines, which sensitize peripheral nociceptors [ 1 , 2 , 19 ] ( Figure 3 a).…”

“…Oxaliplatin upregulates the expression of transient receptor potential melastatin 8 (TRPM8) [ 10 , 16 ], causing cold allodynia. It also activates TTX-R Na + 1.8 (involved in action potential initiation), TTX-R Na +1.6 , and HCN (hyperpolarization-activated channels involved in action potential propagation) while inhibiting TREK1 and TRAAK (potassium channels which restore the membrane potential to the resting state) [ 11 ].…”

Repurposing approved drugs for cancer therapy

“…However, alternatives to oxaliplatin should be sought, as there are severe and long-term neurotoxic AEs associated with this combination. 87 Artemisinin (malaria treatment) derivatives may be an alternative to oxaliplatin, as they are cytotoxic against colon cancer cells lines at low concentrations when used in combination with leucovorin and 5-fluorouracil (FOLNSC combination). 88 …”