Randomized Clinical Investigation of Photobiomodulation (PBM) for the Management of Early Peripheral Neuropathy Related to Medical Oncologic Therapy

Chemotherapy-induced peripheral neuropathy (PN) is a common side-effect of many anti-neoplastic agents; its prevalence is estimated to 20-50% but varies considerably according to many factors and might actually be underreported. PN is increasingly reported as a complication of cancer immunotherapy and various targeted therapies currently used for the treatment of cancer.

PN typically causes disabling, sensitive (paresthesia, dysesthesia, allodynia, loss of sensation), but can also cause motor dysfunction (muscle weakness, fatigue) and autonomic dysfunction (digestive disorders, orthostatic hypotension); once established, regression of symptoms is slow. The pathobiology of chemotherapy-induced PN is mainly unknown despite the documented involvement of neuroinflammatory, mitochondrial, and vascular mechanisms.

PN often compromises quality of life and is a frequent reason for dose reduction, treatment delay, or premature discontinuation of anticancer therapy.

So far, no standard therapy has been recommended, with the possible exception of duloxetine, which has been associated with a modest symptom improvement in cisplatin-treated patients.

In this context, innovative, non-pharmacological, and well-tolerated strategies are needed. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), uses specific wavelengths (red or near-infrared) to modulate cellular activity, promote nerve regeneration, reduce inflammation, and regulate pain. Already included in international recommendations for the management of oral mucositis induced by chemotherapy or radiotherapy, PBM is emerging as a potentially effective alternative for other cancer-related toxicities.

A beneficial effect of PBM on diabetic PN and oxaliplatin-induced PN has been reported.

Argenta et al. published a small randomized sham-controlled trial of PBM on chemotherapy-induced PN that indicated a significant reduction in neuropathy symptoms. They found a significant benefit already after 4 weeks of therapy and patients who crossed over from sham laser experienced similar benefits. In a pilot trial, Lodewijckx et al. found a considerable decrease in symptoms of chemotherapy-induced PN with PBM. The same group reported " promising " results with PBM for the prevention of chemotherapy-induced PN in breast cancer patients.

Therefore, the investigator plan to evaluate the role of PBM administered to patients with " de novo " early signs of PN that are supposed to be related to ongoing neurotoxic anti-cancer therapy (Bortezomib, Cisplatin, Docetaxel, Enfortumag, Halaven, Oxaliplatin, Paclitaxel, Vinblastine, Vincritsine, Vinorelbine).

The project is therefore part of a proactive approach to supportive care aimed at reducing the early symptoms of PN, improving patients' quality of life, and avoiding the interruption or reduction of cancer therapy doses, using a simple, non-invasive device that has the potential for widespread application.

Inclusion criteria

• All the patients admitted for medical oncological therapy to the day care facility (Hôpital de Jour) are eligible for the protocol.
• Age 18 years or above
• Have no documented or observable psychiatric or neurological disorders that might interfere with study participation (e.g., dementia or psychosis)
• Be able to understand the ICF and study-related questionnaires
• Signed informed consent

Exclusion criteria

• severe or unstable cardio-respiratory or musculoskeletal disease
• Peripheral neuropathy previous to chemotherapy
• Receiving potentially neurotoxic therapies other than given for cancer treatment
• Interruption of more than two consecutive laser treatments