| 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 |