Table 1.
Characteristics of included studies describing pharmacological interventions to reduce the incidence of paclitaxel-induced peripheral neuropathy.
| Author | Year | Total sample size | Median age | Population statistics: Percentage of (%) | Intervention | Type of control | Primary outcomes | Outcome Measures | |
|---|---|---|---|---|---|---|---|---|---|
| Female patients | Patients with breast cancer | ||||||||
| Aghili (19) | 2019 | 40 | 45.1 | 40 (100) | 40 (100) | Gabapentin dose (intervention group) or placebo capsules, orally prescribed—300 mg for the 1st day, 600 mg for the 2nd day, and 900 mg divided into three doses for the 3rd up to the 14th day of each cycle. | Placebo | Incidence of both subjective and objective neuropathy. | 1. Relative frequency of neuropathy (subjective) 2. Change in Nerve Conduction Velocity in electrophysiological nerve studies (objective) |
| Anoushirvani (20) | 2018 | 63 | 51.5 | 46 (73) | 36 (57) | Omega-3 capsules of 640 mg three times a day while receiving taxol, or vitamin E supplements at a dose 300 mg twice daily, or placebo capsules for the same period. | Placebo | To assess the efficacy of omega-3 and vitamin E on preventing PIPN via electrophysiological nerve studies and clinical evaluation. | 1. Clinical and electrophysiological evaluation before the onset of chemotherapy and at months 1 and 3; presence of neuropathy and its progression was recorded by the neurologist |
| Argyriou (27) | 2006 | 37 | 57 | 23 (62.2) | 19 (51.4) | Oral supplementation of synthetic DL-alfa-tocopheryl acetate (Eviol soft gelatin capsules) at a dose of 300 mg/day twice daily during chemotherapy and up to 3 months after its suspension. | Standard of care | To estimate the efficacy of vitamin E supplementation in preventing PIPN by determining significant differences in PIPN occurrence between study arms. | 1. Peripheral Neuropathy score 2. Neurological Symptom Score 2. Neurological Disability Score 2. Hughes’ Functional Grading Scale |
| Davis (22) | 2005 | 117 | 58 | 53 (45.3) | Not reported | Study drug was given subcutaneous daily for 7 days starting the day before chemotherapy. Patients were randomized to receive low-dose rhuLIF (2 mg/kg), high-dose rhuLIF (4 mg/kg), or placebo. | Placebo | To observe a change in neurologic assessments, measured using standardized composite peripheral nerve electrophysiology score, from baseline to the end of cycle 4. | 1. Standardized composite peripheral nerve electrophysiology score; based on nerve velocities and amplitudes 2. Vibration perception threshold 3. H-reflex latency 4. Symptom scores 5. Quantitative assessment of neurologic signs 6. NCI CTC 7. Production of rhuLIF antibodies (For toxicity) |
| Ghoreishi (21) | 2012 | 69 | 45.9 | 69 (100) | 69 (100) | Omega-3 fatty acid oral supplements as soft gelatin capsules at a dose of 640 mg three times a day during chemotherapy with paclitaxel and one month after the end of therapy or placebo of Sunflower soft gelatin capsules. | Placebo | To evaluate Reduced Total Neuropathy Score as a measure of the existence and severity of PIPN in patients. | 1. Reduced Total Neuropathy Score (subjective sensory symptoms, pin sensibility, deep tendon reflexes, and nerve conduction studies of sural and peroneal nerves) 2. Nerve conduction study unilaterally using Nicolet/VIASYS Viking Quest electromyography Machine based on standard methods, Serum levels of omega-3 fatty acids - Motor conduction assessment: Distal motor latency, peak to baseline amplitude of compound muscle action potential and motor conduction velocity for tibial, peroneal, and ulnar nerves - Sensory nerve conduction of sural and ulnar nerves: peak-to-peak amplitude measurement of sensory action potentials and sensory conduction velocity (antidromic technique) |
| Hershman (12) | 2018 | 409 | 53 | 409 (100) | 409 (100) | Six active capsules, each containing 590 mg of Acetyl-L-carnitine hydrochloride (provides 500 mg of Acetyl-L-carnitine) and 10 mg of cellulose, were given to the intervention arm, while the control arm received six capsules containing 600 mg of cellulose. | Placebo | To determine the FACT-NTX score at each time point (1 and 2 years). | 11-item FACT-NTX symptom module as a continuous measure (range = 0–44); a lowering in the FACT-NTX score (worse CIPN) of more than 10% or five points is considered clinically significant |
| Hilpert (11) | 2005 | 72 | Not reported | 72 (100) | 0 (0) | I.V. premedication with amifostine (thiophosphate cytoprotectant) 740 mg/m2 or placebo. | Placebo | To assess whether amifostine reduces chemotherapy-induced neurotoxicity of a first-line therapy with standard carboplatin/paclitaxel or with additional epirubicin in advanced ovarian carcinoma in comparison with a placebo treatment, as determined by the measurement of vibration perception thresholds and vibration disappearance thresholds before cycle 4 and after the end of treatment. | 1. Vibration perception thresholds and Vibration disappearance thresholds before cycle 4 and after the end of treatment 2. Patella and Achilles tendon reflex activities 3. Two-point-discrimination [back of the hands, 10, 5, 3, and 1.5 cm separation; tibia (vertical), 10 and 4 cm separation] 4. Specific sensory symptoms and fine and global motor activities, surveyed via a patient questionnaire 5. EORTC QLQ-C30 questionnaire 6. Toxicity including sensory neuropathy and pain categories according to NCI-CTC |
| Khalefa (13) | 2020 | 65 | Not reported | 65 (100) | 65 (100) | For the intervention groups, the low-dose group received paclitaxel in addition to N−acetylcysteine 600 mg twice daily for 12 weeks while the high-dose group received N−acetylcysteine 1,200 mg twice daily for 12 weeks. The control group received paclitaxel only. | Standard of care | To determine the incidence of grade II or more PIPN at 12 weeks. | 1. CTCAE v4.0, assessed weekly for 12 weeks 2. Modified Total Neuropathy Score at baseline and after 6 and 12 weeks 3. FACT/Gynecologic Oncology Group-NTX subscale assessed at baseline and after 6 and 12 weeks 4. Blood samples withdrawn from patients at baseline and after 12 weeks to evaluate serum levels of malondialdehyde and nerve growth factor using commercial spectrophotometric and ELISA kits, respectively |
| Leal (10) | 2014 | 185 | 63 | 150 (81) | Not reported | Patients received glutathione 1.5 g/m2 or placebo (100 ml of 0.9% saline) intravenously over 15 min immediately before second dose of chemotherapy. | Placebo | To measure sensory chemotherapy-induced peripheral neuropathy as measured repeatedly by the sensory subscale of the EORTC QLQ-CIPN20 during the first 6 cycles of chemotherapy. | 1. EORTC QLQ-CIPN20 1. FACT for Patients with Ovarian Cancer assessments 3. CTCAE v4.0 |
| Loven (26) | 2009 | 43 | 59 | 43 (100) | 0 (0) | On the first day of chemotherapy, every participant received one batch containing eight bottles of either glutamate 500 mg or identical-looking placebo capsules: 6 bottles for 6 cycles of chemotherapy, and 2 bottles for supplementation when capsules of a previous bottle were not enough due to delay of chemotherapy. | Placebo | To achieve a 65% reduction in the rate of patients with CIPN in the Glutamate group as compared with Placebo group as defined either by the rate of patients with signs and symptoms corresponding to severity scores 2–3 or by the rate of appearance of impaired electrophysiological features. | 1. Rate of patients with signs and symptoms corresponding to severity scores 2–3 2. Rate of appearance of impaired electrophysiological features 3. Standard sensory–motor nerve conduction study using a Dantec Keypoint or Nicolet Voyager Electromyography 4. Specially designed questionnaire regarding the presence of tingling, numbness, pain, and muscle weakness |
| 1 capsule 3x daily, either half an hour before or 2 h after a meal, starting on that day. | |||||||||
| This supplementation treatment was continued throughout the period of 6 cycles of chemotherapy and until 3 weeks later. | |||||||||
| Pachman (8) | 2017 | 45 | 54.9 | 45 (100) | 45 (100) | 200 mg of minocycline (x2 100 mg capsules) on Day 1 followed by 100 mg twice daily or matching placebos until the 12 weeks of chemotherapy were completed. | Placebo | Obtain pilot data regarding the possible effect of minocycline on the prevention of PIPN and Paclitaxel acute pain syndrome. | 1. Daily average Area Under Curve pain score 1. Acute pain syndrome questionnaire daily during chemotherapy to measure Paclitaxel acute pain syndrome 1. EORTC QLQ-CIPN20 questionnaire |
| Shinde (9) | 2016 | 46 | 53.7 | 46 (100) | 46 (100) | Pregabalin 75 mg or placebo twice daily, starting on the first night of chemotherapy and continuing through the planned 12 weeks of chemotherapy. During the 13th week, the dose was decreased to once a day at bedtime, after which patients went off-study. | Placebo | To assess the effectiveness of pregabalin on the Paclitaxel acute pain syndrome via the maximum of the worst pain scores for the week following the first cycle of paclitaxel administration, as measured by a question on the daily post-paclitaxel questionnaire. | 1. EORTC QLQ-CIPN20 questionnaire 2. Patient-reported acute pain syndrome questionnaire 3. Maximum of the worst acute pain scores 4. Adverse events per CTCAE criteria |
CIPN, Chemotherapy-Induced Peripheral Neuropathy; NCI-CTC, National Cancer Institute Common Toxicity Criteria; CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; ELISA, Enzyme-linked immunosorbent assay; EORTC QLQ, European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire; FACT-NTX, Neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane; PIPN, Paclitaxel-Induced Peripheral Neuropathy; rhuLIF, recombinant human leukemia inhibitory factor.