BACKGROUND:Chemotherapy-induced oral thermal hyperalgesia (OTH) is a common and debilitating side effect of platinum-based anticancer agents. This study evaluated the efficacy of oral cryotherapy in preventing OTH during oxaliplatin chemotherapy infusion.

METHODS:Patients with gastrointestinal cancer treated with biweekly oxaliplatin (85 mg/m2 over 120 minutes) at Abramson Cancer Center at the University of Pennsylvania were randomized to receive oral cryotherapy (ice chips) during oxaliplatin infusion or standard-of-care treatment. All patients completed baseline questionnaires regarding oral and peripheral symptoms and on-treatment questionnaires on day 1 of each subsequent chemotherapy cycle. Those in the treatment arm were asked to document how long they kept the ice chips in their mouths (0,<30, 30, 60, 90, or 120 minutes) and to report their discomfort associated with oral cryotherapy. Evaluable patients were those who had completed at least 2 cycles of oxaliplatin therapy.

RESULTS:Of 62 randomized patients with a variety of gastrointestinal malignancies, 50 (25 per treatment arm) were evaluable for efficacy. The rate of patients with oral symptoms after the first treatment cycle was significantly lower in the intervention arm (n=8; 32%) than in the control arm (n=18; 72%), meeting the primary study objective (P=.01). The magnitude of difference in symptom scores before versus after the first treatment cycle was significantly less in the intervention versus control arm (P=.001). No difference in oral symptoms over time was seen between the intervention and control groups (P=.20), although a high attrition rate was noted. Duration of ice chip exposure was associated with improved oral symptoms over time (P=.02).

CONCLUSIONS:Oral cryotherapy is a tolerable and cost-effective method of diminishing OTH in patients receiving oxaliplatin chemotherapy, and seems to be most effective in the early stages of treatment.

Oxaliplatin, a platinum-based anti-cancer drug, induces peripheral neuropathy as a side effect and causes cold hyperalgesia in cancer patients receiving anti-cancer chemotherapy. In oxaliplatin-treated mice, aluminum was accumulated in the dorsal root ganglia (DRG), and accumulated aluminum in DRG or other organs aggravated oxaliplatin-induced neuropathic pain. To investigate whether aluminum oxalate, which is the compound of aluminum and oxaliplatin, might be the peripheral neuropathy inducer, the withdrawal responses of mice to coldness, the expression of transient receptor potential ankyrin 1 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays in DRG were analyzed in mice administered with aluminum oxalate. In addition, the concentrations of aluminum in aluminum oxalate-treated mice were significantly increased compared to those of mice treated with aluminum chloride. To alleviate neuropathic pain, glutathione (GSH), known as an antioxidant and a metal chelator, was injected into oxaliplatin-treated mice. The concentrations of aluminum in the DRG were decreased by the chelation action of GSH. Taken together, behavioral and molecular analyses also supported that aluminum accumulation on the DRG might be a factor for neuropathic pain. This result also suggested that the aluminum chelation by GSH can provide an alleviatory remedy of neuropathic pain for cancer patients with oxaliplatin-induced neuropathic pain.

BACKGROUND:Oxaliplatin is frequently used in the treatment of metastatic colorectal cancer. However, peripheral neuropathy is a severe adverse effect of oxaliplatin that may persist and impact quality of life.

OBJECTIVE:To assess the potential effects of ultrasound acupuncture for the alleviation of symptoms related to oxaliplatin-induced peripheral neuropathy (OIPN) among metastatic colorectal cancer patients.

DESIGN:A prospective cohort pilot study.

SETTING:Education and research hospital.

PARTICIPANTS:Patients with a diagnosis of stages II-IV colorectal cancer treated with oxaliplatin-based treatment regimens and with the presence of OIPN symptoms (n = 17).

INTERVENTIONS:Pulsed therapeutic ultrasound (1 MHz) at bilateral acupuncture points of PC6, PC7, BL60 and KI1 were administered for 5 min/point daily for 12 d.

MAIN OUTCOME MEASURES:Pain Quality Assessment Scale (PQAS), Chemotherapy-induced Neurotoxicity Questionnaire (CINQ), quantitative touch-detection threshold, cold-trigger pain withdrawal latency and quality of life (EORTC QLQ-C30) were measured at baseline (day 0), pre-intervention (day 12, post wash-out period), post-intervention (day 24) and final follow-up (day 54). A P values of less than 0.05 was considered statistically significant.

RESULTS:Scores of PQAS and CINQ significantly improved post ultrasound acupuncture at post-intervention and follow up compare to both base-line and pre-intervention. Similar trends were also observed for the Quantitative Sensory Testing where touch-detection threshold significantly decreased and cold-trigger pain withdrawal latency significantly increased post ultrasound acupuncture. Patients also showed an improvement on Quality of Life outcomes as measured by QLQ-C30 post-intervention and at follow up.

CONCLUSIONS:Ultrasound acupuncture could potentially be an effective intervention for OIPN symptoms for colorectal cancer patients. However, larger and randomized clinical trials with placebo controls are needed to confirm such effect. This article is protected by copyright. All rights reserved.