| Reference (year, country) | Study Design | N | Treatment | CIPN assessment | Cancer and ChT regimen | Primary Efficacy Measures | Outcomes (effectiveness) | Side effects and interactions | Study quality | Quality criteria items |
| Yang Y. (2012, China) [19] | Unicentric trial, single-arm. | 39 | Duloxetine 60 mg/day (30 mg/day in first week, and 60 mg/day in subsequent 11 weeks) | Symptomatic CIPN, with NCI-CTCAE v3.0 grade 1 - 3 | Colon cancer, in stage III or IV, submit to oxaliplatin-based ChT | VAS and NCI-CTCAE v3.0, on baseline and at 12 weeks | >30% VAS score reduction in 63,3% and NCI-CTCAE v3.0 grade improvement in 47.4% of pts | Discontinuation in 23% by adverse effects (dizziness/nausea: 10%, somnolence: 5%, insomnia: 5%) | 13 | 1, 2, 4, 5, 6, 9, 13, 14, 15, 16, 17, 18, 19 |
| Smith E. (2013, USA) [20] | Multicentric, phase III randomized, double-blind, placebo-controlled, crossover trial | 231 | Duloxetine 60 mg/day (30 mg/day in 1st week, and 60 mg/day in subsequent 4 weeks) | CIPN with NCI-CTCAE v3.0 grade ≥1; and an average pain score ≥4, for ≥3 months beyond ChT completion | Any cancer and stage. Pts submitted to ChT with paclitaxel, oxaliplatin, docetaxel, nab-paclitaxel, or cisplatin. | BPI-SF “average pain” (based to NRS), weekly | Any decrease pain in 59% of pts treated with duloxetine vs. 38% of pts on placebo arm, with a mean decrease in average pain of 1.06 and 0.34, respectively | Duloxetine discontinuation in 11% by adverse effects (fatigue: 7%, insomnia: 5%, nausea: 5%) | 16 | 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 13, 16, 17, 18, 19 |
| Hirayama Y. (2015, Japan) [21] | Unicentric, phase II randomized, open-label, crossover trial (duloxetine vs. vitamin B12) | 34 | Duloxetine 40 mg/day (20 mg/day in first week, and 40 mg/day in subsequent 3 weeks) | Descriptors of neuropathic numbness or pain | Any cancer and stage. Pts submitted to ChT with paclitaxel, oxaliplatin, vincristine, or bortezomib. | VAS, on baseline and weekly | >30% VAS score reduction in numbness and pain in 80% and 73% of pts, respectively (compared to 24 and 18% related to vitamin B12) | Duloxetine discontinuation in 15% by adverse effects (fatigue: 18%) | 11 | 1, 2, 3, 4, 5, 6, 7, 13, 16, 17, 18 |
| Kautio A. L. (2008, Finland) [29] | Unicentric, randomized, double-blind, placebo-controlled trial | 44 | Amitriptyline (10 - 50 mg/day) for 8 weeks | Severity of CIPN (pain, numbness, and tingling) ≥ 3 out of 10 | Any cancer and stage. Pts treated with neurotoxic ChT during ≥2 months | Neuropathic symptoms, assessed by numeric scales (0 - 10), twice a week | Nonsignificant trend toward better global improvement with amitriptyline | 15 of the 17 pts were on the target dose (50 mg/day). | 10 | 1, 2, 4, 5, 6, 7, 9, 13, 16, 19 |
| Rao R. (2007, USA) [25] | Multicentric, phase III randomized, double-blind, placebo-controlled, crossover trial | 115 | Gabapentin (300 mg/day with dose incremented in 3 weeks, up to 2700 mg/day) for 6 weeks | >1 month symptomatic CIPN, with pain NRS ≥4 or ENS ≥1 | Any cancer and stage. Active or previous treatment with neurotoxic ChT | NRS and ENS (weekly) | No significant differences in primary endpoints | Adverse events occurred at relatively equivalent rates in both groups. | 13 | 1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 16, 18, 19 |
| Saif M. (2010, USA) [26] | Unicentric trial, single-arm | 23 | Pregabalin 50 mg tid 150 mg tid | CIPN with NCI-CTCAE v3.0 grade 2 - 3 | Gastrointestinal cancer pts treated with oxaliplatin-based ChT | NCI-CTCAE v3.0, every 2 weeks | NCI-CTCAE v3.0 grade improvement in 48% of pts | Discontinuation in 3 pts. The 3 more frequent side effects are: dizziness (57%), headache (26%), somnolence (22%). | 11 | 1, 2, 4, 5, 6, 9, 13, 14, 16, 17, 18 |