Prevention Of Chemotherapy-induced Neuropathy Research Articles

Paclitaxel-induced hyposensitivity to nociceptive chemical stimulation in mice can be prevented by treatment with minocycline.

Development of peripheral neuropathy, which can present as painful neuropathy or loss of sensation, sometimes limit the use of paclitaxel in the treatment of solid tumors such as breast cancer. Previous studies reported development of thermal hyperalgesia in mice treated with paclitaxel. In this study an automated flinch detection system for the formalin test (20 μl of 5% formalin injected subcutaneously into the paw dorsum) was used to evaluate chemical nociception in BALB/c mice treated with paclitaxel 2 mg/kg alone or coadministered with minocycline 50 mg/kg, intraperitoneally for 5 consecutive days. Reaction latency to thermal stimuli (hot-plate) was also measured. Injection of formalin resulted in biphasic paw flinches; phase 1 (1–9 minutes) and phase 2 (10–40 minutes). Treatment with paclitaxel reduced cumulative flinches in both phases 1 and 2 by 28% and 43%, respectively at day 7. However, treatment with paclitaxel also induced thermal hyperalgesia. Co-administration of paclitaxel with minocycline prevented development of both paclitaxel-induced hyposensitivity to chemical nociception and thermal hyperalgesia. In conclusion, the results indicate paclitaxel induces chemical hyposensitivity and thermal hyperalgesia in mice. Minocycline protected against paclitaxel-induced chemical hyposensitivity and thermal hyperalgesia, thus, providing further support of the usefulness of the drug in prevention of chemotherapy-induced neuropathy.

A randomized, double-blinded, placebo-controlled trial of oral alpha lipoic acid to prevent platinum-induced polyneuropathy.

9010 Background: Platinum-induced peripheral neuropathy may cause pain, function loss, and can be a dose-limiting factor for cancer treatment. The neurotoxicity can be irreversible; therefore prevention of chemotherapy-induced neuropathy is necessary. Our aim is to determine if α-lipoic acid (ALA, thioctic acid) can prevent peripheral neuropathy for patients (pts) receiving platinum-containing chemotherapy. Methods: Adult cancer pts were randomized to receive either 600 mg ALA or placebo (2 large pills) three times a day for 24 weeks while receiving platinum-base chemotherapy. Neuropathy was measured by FACT/GOG-NTX score and NCI-CTC neurotoxicity grade. Results: Of 243 pts randomized, 121 pts (51%) completed treatment for 12 weeks and 84 pts (35%) for 24 weeks. Of these, 70 pts completed FACT/GOG-NTX assessments at baseline and at 24 weeks. At baseline, the ALA (n =122) and placebo (n =121) groups were comparable for age (55±11 vs. 57±12 years), gender (54% vs 52% male), prior platinum exposure, and FACT/GOG-NTX score. At 24 weeks, only 34 evaluable pts remained in the ALA group, and 36 in the placebo group (p= 0.75). Pill size and dose frequency were frequent concerns regarding adherence. No statistical difference was noted in dose intensity for the oxaliplatin arm of the ALA group and the placebo group (median of 765 mg/m2 vs. 1020 mg/m2, p=0.18). No significant differences were noted for either FACT/GOG-NTX scores (p=0.70), neurotoxicity (p=0.87), or best tumor responses between the 2 groups (p=0.85). Conclusions: Oral ALA 600 mg PO TID was ineffective at preventing neurotoxicity caused by oxaliplatin or cisplatin. Intense schedules of oral agents in the symptom/toxicity prevention setting created adherence challenges due to pill size and frequency of administration. Poor adherence might affect the power to detect ALA’s effectiveness in this trial. Innovative drug delivery and trial designs are needed to further explore alpha lipoic acid in the prevention and/or reduction of chemotherapy-induced neuropathy.

Prevention of Chemotherapy-Induced Neuropathy: Leukemia Inhibitory Factor

Peripheral neurotoxicity is a dose-limiting and disabling side effect of several important chemotherapeutic agents. In particular, vincristine, cisplatin, oxaliplatin, paclitaxel, and docetaxel are frequently used antineoplastic agents, which are known causes of a peripheral neuropathy. The recently