Table 2.
The therapeutic drugs for paclitaxel-induced peripheral neuropathy in clinical experiments.
| Investigational Drug | Dose (Preventive or Curative) |
Chemotherapy | Study Design | Patient Number | Summary | References |
|---|---|---|---|---|---|---|
| Acetyl-L-carnitine | 3000 mg daily, p.o. (preventive) |
Taxanes | Randomized, double-blind, placebo-controlled, multicenter study | 409 | Significant reduction in NTX scores (worsening of peripheral neuropathy) >2 years | [111] |
| Amifostine | 910 mg/m2, i.v., before the paclitaxel administration (preventive) |
Carboplatin/paclitaxel | Randomized, controlled study | 38 | Significant improvements in paresthesia and sensory motor impairment. | [112] |
| 910 mg/m2, i.v., before the paclitaxel administration (preventive) |
Paclitaxel | Randomized, controlled study | 37 | No significant difference in any of the measures of neurotoxicity. | [113] | |
| Duloxetine | 40 mg daily, p.o. (20 mg/day for the first week) (curative) |
Oxaliplatin, paclitaxel, vincristine, or bortezomib | Randomized, open-label, crossover study (vs vitamin B12) | 34 | Significant improvements in numbness and pain | [114] |
| 60 mg/day, p.o., (30 mg/day for the first week) (curative) |
Taxane or platinum | Randomized, double-blind, placebo-controlled, crossover study | 231 | In all patients, RRs (95% CI) of experiencing 30% and 50% pain reduction were 1.96 (1.15–3.35) and 2.43 (1.11–5.30), respectively In taxane-treated patients, RRs (95% CI) of experiencing 30% and 50% pain reduction were 0.97 (0.41–2.32) and 1.22 (0.35–4.18), respectively (not significant) |
[115] | |
| Gabapentin | 900 mg daily, p.o., (preventive) |
Paclitaxel | Randomized, double-blind, placebo-controlled study | 40 | Significant improvements in the incidence of grades 2–3 neuropathy and NCV changes | [116] |
| Glutamate | 1500 mg daily, p.o., (preventive) |
Paclitaxel | Randomized, double-blind, placebo-controlled study | 43 | No significant difference in the frequency of signs or symptoms between the two groups | [117] |
| Glutathione | 1.5 g/m2, i.v., immediately before chemotherapy (preventive) |
Carboplatin/ paclitaxel |
Randomized, double-blind, placebo-controlled study | 185 | No significant differences in acute pain score and EORTC QLQ-CIPN20 scores compared to the placebo group | [118] |
| Minocycline | 200 mg daily, p.o., (preventive) |
Paclitaxel | Randomized, double-blind, placebo-controlled, multicenter study | 47 | Significant improvements in acute pain score No significant differences in sensory neuropathy score of the EORTC QLQ-CIPN20 compared to the placebo group |
[119] |
| N-acetyl cysteine | 1200 mg daily or twice daily, p.o., (preventive) |
Paclitaxel | Randomized, controlled, open label study | 75 | Significant improvements in incidence of grades 2–3 neuropathy, mTNS, and QOL scores Significant increase in serum NGF and decrease in serum MDA |
[120] |
| Omega-3 fatty acid | 1920 mg daily, p.o., (preventive) |
Paclitaxel or oxaliplatin | Meta-analysis | 116 (two trials) |
Significant improvements in the incidence of peripheral neuropathy and SNAP amplitudes | [121] |
| 1920 mg daily, p.o., (preventive) |
Paclitaxel | Randomized, double-blind, placebo-controlled study | 57 | Significant improvements in neuropathy incidence | [122] | |
| Oral nutritional supplement containing EPA | p.o., (preventive) |
Paclitaxel or cisplatin/carboplatin | Randomized, controlled study | 92 | Significant improvement in neuropathy | [123] |
| PARP inhibitors (olaparib or veliparib) | N.A. | Paclitaxel | Meta-analysis | 843 (five trials) |
Did not reduce the risk of chemotherapy-induced peripheral neuropathy | [124] |
| Pregabalin | 150 mg daily, p.o., (curative) |
Paclitaxel or docetaxel | Randomized, double-blind, controlled study (vs duloxetine group) | 82 | Improvements in NCI-CTCAE grade and PNQ scores were more significant with pregabalin in comparison to duloxetine | [125] |
| 150 mg daily, p.o., (preventive) |
Paclitaxel | Randomized, double-blind, placebo-controlled, multicenter study | 46 | No significant differences in acute pain score and EORTC QLQ-CIPN20 scores compared to the placebo group | [126] | |
| Recombinant human LIF | 2 or 4 µg/kg, s.c., (preventive) |
Carboplatin/ paclitaxel |
Randomized, double-blind, placebo-controlled study | 117 | No significant difference in CPNE or any of the individual neurologic testing variables | [127] |
| Vitamin E | 600 mg daily, p.o., (preventive) |
Paclitaxel | Randomized, controlled study | 32 | Significant improvements in the incidence of neuropathy and PNP scores | [128] |
| 600 mg daily, p.o., (preventive) |
Cisplatin or paclitaxel | Randomized, controlled study | 31 | Significant improvements in incidence and neuropathy scores | [129] |
Abbreviations: 95% CI, 95% confidence interval; CPNE, composite peripheral nerve electrophysiology; EORTC QLQ-CIPN20, European Organisation for Research and Treatment of Cancer, Quality of Life-Chemotherapy-Induced Peripheral Neuropathy 20; EPA, eicosapentaenoic acid; LIF, leukemia inhibitory factor; MDA, malondialdehyde; mTNS, modified total neuropathy score; NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events; NCV, nerve conduction velocity; NGF, nerve growth factor; NTX score, neurotoxicity score; PARP, poly ADP-ribose polymerase; PNP score, peripheral neuropathy score; PNQ, patient neurotoxicity questionnaire; QOL, quality of life; RR, relative risk; SNAP, sensory nerve action potential.