TENS and Compression for Established Oxaliplatin-Induced Peripheral Neuropathy

Comparative Effects of Transcutaneous Electrical Nerve Stimulation, Compression, and Sequential TENS Plus Compression on Established Oxaliplatin-Induced Peripheral Neuropathy in Patients With Metastatic Gastrointestinal Cancer: A Four-Arm Randomized Controlled Trial

Chemotherapy-induced peripheral neuropathy is a clinically important adverse effect of oxaliplatin-based chemotherapy that may cause sensory symptoms, neuropathic pain, functional limitations, and reduced quality of life. This randomized, open-label, four-arm parallel study evaluated the comparative effects of transcutaneous electrical nerve stimulation (TENS), compression, sequential compression followed by TENS, and usual care in 140 adults with metastatic gastrointestinal cancer who developed Grade 2 or higher chemotherapy-induced peripheral neuropathy after the first cycle of oxaliplatin-based chemotherapy. Participants were allocated in a 1:1:1:1 ratio. The primary outcome was the change in the EORTC QLQ-CIPN20 total score from baseline before Cycle 2 to Cycle 6. Quality of life, neuropathy grade, and neuropathic pain were evaluated as secondary outcomes. A prespecified exploratory assessment was also conducted 6 months after Cycle 6.

This open-label, randomized, four-arm parallel study was conducted to evaluate supportive interventions for the management of established chemotherapy-induced peripheral neuropathy in patients receiving oxaliplatin-based chemotherapy. Eligible participants had metastatic gastrointestinal cancer, had received one cycle of FOLFOX or FOLFIRINOX, and had Grade 2 or higher chemotherapy-induced peripheral neuropathy according to NCI-CTCAE v5.0 before the Cycle 2 intervention.

A total of 140 participants were allocated in a 1:1:1:1 ratio to the TENS group, compression group, sequential compression followed by TENS group, or usual care control group, with 35 participants in each group. Participants remained in their assigned parallel groups throughout the study.

The TENS group received 120 minutes of transcutaneous electrical nerve stimulation at each scheduled intervention session. Stimulation was delivered at 40 Hz with a pulse width of 100 microseconds, and intensity was individually adjusted to produce a strong but comfortable sensory sensation without visible muscle contraction.

The compression group received bilateral compression of the hands and feet for 120 minutes using surgical gloves one size smaller than the individually determined glove size and graduated compression stockings providing 23-32 mmHg of pressure.

The sequential compression followed by TENS group received 90 minutes of compression followed by 90 minutes of TENS, for a total intervention duration of 180 minutes. The usual care control group received no study-specific TENS or compression intervention.

Outcomes were assessed at baseline before Cycle 2 and before Cycles 3, 4, 5, and 6. The primary outcome was the change in the EORTC QLQ-CIPN20 total score from baseline before Cycle 2 to Cycle 6. Secondary outcomes included EORTC QLQ-C30 scale scores, NCI-CTCAE v5.0 peripheral sensory neuropathy grade, and DN4 total score and neuropathic pain positivity. All outcome measures were also reassessed at a prespecified exploratory follow-up 6 months after Cycle 6.

Inclusion Criteria:

• Aged 18 years or older
• Diagnosed with metastatic gastrointestinal cancer, including gastric, pancreatic, colon, or rectal cancer
• Scheduled to receive six cycles of oxaliplatin-based chemotherapy with FOLFOX or FOLFIRINOX
• Having received one cycle of oxaliplatin-based chemotherapy
• Having Grade 2 or higher chemotherapy-induced peripheral neuropathy according to NCI-CTCAE v5.0 before the Cycle 2 intervention
• Eastern Cooperative Oncology Group performance status of 0-2
• Having provided written informed consent to participate

Exclusion Criteria:

• Having a diagnosed psychiatric disorder that could interfere with informed consent, communication, or adherence to the study procedures
• Having a cardiac pacemaker or another implanted electronic device contraindicating TENS
• Having pre-existing peripheral neuropathy before the initiation of oxaliplatin-based chemotherapy or neuropathy attributable to another cause
• Having diabetes mellitus
• Having peripheral vascular disease or another clinically significant circulatory disorder affecting the hands or feet
• Having a skin lesion or other skin condition at the sites where TENS electrodes or compression garments would be applied