Pregabalin

Evaluate the effect on pregabalin given three days prior and three days after each oxaliplatin dose on oxaliplatin-induced peripheral neuropathy

Pregabalin versus placebo given three days prior to and three days after oxaliplatin infusion on weeks 1, 3, and 5 of an 8-week cycle.

• N = 199 enrolled, 143 in the final analysis (56 participants did not receive at least one full cycle of FOLFOX 
• AGE: Median = 57 years (mean = 57.13, SD = 10.51)
• MALES: 99 patients (49.7%)  
• FEMALES: 100 (50.3%)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: CRC, newly diagnosed stage III/IV
• OTHER KEY SAMPLE CHARACTERISTICS: Dose of pregabalin was 150-600 mg daily; placebo was also 150-600 mg daily with drug 1 and 150 mg  dose for drug 2.

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Multiple sites; Sao Paulo, Brazil

PHASE OF CARE: Active anti-tumor treatment

Randomized, placebo controlled trial

Main outcome was pain level based on the visual analog scale (rating 0-10) and the brief pain inventory (BPI). Secondary endpoints  were the presence of pain from neuropathy as well the severity of pain based on the Douleur Neuropathique–4 (DN-4), the short-form McGill Pain Questionnaire (MPQ), the Neuropathic Pain Symptom Inventory (NPSI), and any changes in the nerve conduction studies as well as subjective side effect profile.

The pain intensity level of the pregabalin group was 1.03 (95% CI [0.76, 1.26]) and was 0.85 in the placebo group (95% CI [0.64, 1.06]). Quality-of-life scores did not differ between the two groups (placebo QOL was 76.9 [SD = 23.1] and the pregabalin QOL was 79.4 [SD = 20.6]). There were no significant differences in any of the outcome measures.

The intervention was safe, but did not decrease the pain severity or incidence of oxaliplatin-induced peripheral neuropathy.

• Findings not generalizable
• Other limitations/explanation: Only relevant to oxaliplatin

Pregabalin may be safe to take, but does not prevent neuropathy in those receiving oxaliplatin.

To compare the efficacy of amitryptylline, gabapentin, and pregabalin in patients with cancer experiencing neuropathic pain

Patients were randomly assigned to amitryptyllin (AT), gabapentin (GB), pregabalin (PG), or placebo. AT was given at 50 mg/day for one week, then increased incrementally to 100 mg/day. GB was given at 900 mg/day for one week in divided doses, then increased to 1,800 mg/day by week 3. PG was given at 150 mg/day for one week, then increased to 600 mg/day by week 3. The control group received placebo capsules. Morphine was used as rescue pain medication as needed. Patients were evaluated weekly for four weeks.

• The study reported on 120 patients.
• Information on patient age and key disease characteristics was not provided.

• Single site    
• Setting not specified
• India

The study has clinical applicability for late effects and survivorship.

The study was a placebo-controlled, randomized trial.

• Visual analog scale (VAS) to measure pain globally as well as burning, lancinating pain and dysesthesia
• Eastern Cooperative Oncology Group (ECOG) score for functional capacity
• Global satisfaction rating on a five-point verbal scale

VAS scores decreased in all groups. In week 4, those on pregabalin had significantly lower VAS scores than other groups, and scores declined by 4–5 points (p < 0.03). By the third visit, the percentage of patients who required morphine rescue increased: 46.7% with AT, 23.3% with GB, 16.7% with PG, and 100% with placebo. Lancinating pain incidence was lowest in the PG group. There were significantly fewer patients with dysesthesia in the PG group (6.7%) compared to the GB and placebo groups after four weeks. The percentage of patients with allodynia declined in all groups. The PG group showed a statistically significant improvement in ECOG score compared to all other groups (p < 0.001). Satisfaction was similar in all groups, and there were no significant differences in adverse reactions, with a gradual increase in all groups over time. Adverse effects were somnolence, dizziness, nausea, constipation, and dry mouth.

All of the drugs tested here demonstrated some efficacy in improving neuropathic symptoms. In several areas, it appears that pregabalin was more effective than gabapentin, opioid monotherapy, and amitryptylline. All medications were given in combination with opioids for pain management.

• No information of opioid dosages in each group was provided for comparison.
• The follow-up period of four weeks was relatively short, given the usual duration of symptoms.
• No information was provided regarding the causes of peripheral symptoms (whether they were chemotherapy-induced or related to other causes).

All of the medications examined in this study were effective and had a morphine-sparing effect in the treatment of neuropathic pain and other symptoms. Pregabalin was more effective than other alternatives tested in some areas. As all patients in this study received opioids for pain rescue, it should be noted that essentially all medications compared were given in combination with opioids.

The study goal was to assess the efficacy of pregabalin in the treatment of oxaliplatin-induced neurotoxicity.

Patients receiving oxaliplatin with grade 2 and 3 sensory neuropathy were treated with pregabalin up to a target dose of 150 mg orally three times a day. Neurologic symptoms were serially evaluated before treatment initiation with pregabalin and every two weeks thereafter, recording intensity and duration of the symptom. Interference with activities of daily living (ADLs) were evaluated. Patients started pregabalin at 50 mg three times per day. If tolerated, the dose was increased by 50 mg increments until symptoms improved to a max of 150 mg three times per day.

• The sample consisted of 23 patients (14 men, 9 women) with gastrointestinal cancer.
• Age range of the participants was 50–71 years.
• Patients had grade 2 or 3 oxaliplatin-induced sensory neuropathy based on National Cancer Institute common toxicity criteria.
• Patients were excluded if they had preexisting neuropathy from diabetes, alcoholism, CNS disease, or neurotoxic chemotherapy.

The study was conducted at an outpatient university setting in the United States.

The study had a prospective trial design.

National Cancer Institute common toxicity criteria

Five of the 23 participants were escalated to 150 mg of pregabalin with benefit and tolerance. Seven of the 23 escalated to 100 mg with benefit and tolerance. Four stopped due to no benefit, five could not be increased above 50 mg three times daily, two continued at this dose, and three stopped because of CNS side effects. Onset of benefit observed in 2–6 weeks. Three patients' neuropathy improved from grade 3 to grade 2, two patients improved from grade 3 to grade 1, and six patients improved from grade 2 to grade 1. No patients remained at grade 3 and five remained stable at grade 2. The five most common toxicities of pregabalin were dizziness, headache, somnolence, dry mouth, ataxia, and tremor.

Pregabalin at a dose of 100 mg–150 mg three times daily appears to decrease sensory neuropathy in some patients receiving oxaliplatin. Pregabalin was associated with side effects that limited the ability to tolerate the medication or dose escalation.

• The study had a small sample size (less than 30).
• The study also lacked a comparison or control group.
• The NCI toxicity criteria may not be valid to measure neuropathy.
• Results may be difficult to generalize to other groups of patients with cancer.

Pregabalin may be another alternative in treating chemotherapy-induced neuropathy for some patients. Findings suggest that pregabalin is not effective for everyone. In addition, the drug is expensive and is a controlled substance, which can limit the use. Pregabalin has side effects that need to be considered, including CNS side effects that required drug discontinuation. Patients receiving this agent need to be monitored appropriately for both effectiveness and potential side effects.

To investigate the potential role of pregabalin in the prevention of chemotherapy-induced neuropathy

Patients were randomized to receive placebo or pregabalin 75 mg twice daily starting on the first night of chemotherapy and throughout 12 weeks of chemotherapy. In week 13, the dose was reduced to once daily at bedtime. Patients were instructed to use acetaminophen or oxycodone as needed for breakthrough pain. For the first six days, pain severity and analgesic use were obtained daily; on day 8, they were obtained prior to each subsequent paclitaxel treatment; and they were obtained for six months 30 days after the completion of paclitaxel treatment.

• N = 41 
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer receiving adjuvant or neoadjuvant paclitaxel 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients with a history of peripheral neuropathy, prior exposure to neurotoxic chemotherapy, or diabetes were excluded.

• SITE: Multi-site  
• SETTING TYPE: Outpatient
• LOCATION: New York

PHASE OF CARE: Active antitumor treatment

Double-blind, placebo-controlled trial

• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QLC)-CIPN20 
• Common Terminology Criteria for Adverse Events (CTCAE), version 4.0

No differences existed between groups in worst, average, or least pain scores, or in analgesic use. No differences existed in the motor neuropathy or autonomic neuropathy subscale scores of the EORTC instrument. No significant differences were observed in adverse events.

The findings did not support any effect of pregabalin for the prevention of chemotherapy-induced neuropathic symptoms.

• Small sample (< 100)
• The doses of pregabalin used here may have been insufficient to show an effect.

Professional guidelines have suggested that gabapentinoids may be considered as an option to treat chemotherapy-induced neuropathy, although their effectiveness has not been established. This study provides limited evidence to suggest that pregabalin, a type of gabapentinoid, is effective for the prevention or reduction of paclitaxel-induced neuropathic symptoms. Given these results, it may not effectively treat established neuropathic symptoms. Currently, limited treatment options exist for the prevention or management of chemotherapy-induced peripheral neuropathy. Nurses need to be aware of chemotherapy agents that have neurotoxic effects, and monitor patients for early detection of such effects to identify the need for potential treatment dose modification.

The goal of the study was to determine utility of substitution of pregabalin for gabapentin therapy in relief of neuropathic pain.

All patients starting on gabapentin and all patients already using gabapentin as monotherapy were offered the choice of replacing their gabapentin with pregabalin. Comparison was made between the groups switched to pregabalin and a cohort group of patients with peripheral neuropathy and pain receiving only gabapentin without a switch to pregabalin.

• The total sample consisted of 40 participants (68% female, 32% male).
• The mean age of those classified as gabapentin responders was 57.3 years (SD = 9.2).
• The mean age of those classified as nonresponders was 54.5 years (SD = 9.8).
• The mean age of those in the gabapentin cohort was 58.4 years (SD = 11.1).
• 38 patients were diabetic, 11 had MGUS, 6 had vitamin B12 deficiency, 34 had idiopathic peripheral neuropathy, 2 had autoimmune conditions, and 2 had multiple myeloma.

The study was conducted at a single site in Canada.

Cohort study

• Toronto Clinical Scoring System (TCSS) was used to measure diabetic peripheral neuropathy.
• EQ-5D: European Quality of Life–5 domains
• EQ-5D VAS: European Quality of Life–Pain Visual Analog Scale

Both gabapentin responder and nonresponders groups had additional pain relief of about 25% following substitution of pregabalin after 6 and 12 months. The percentage of improvement on the EQ-5D VAS was significant (p < 0.025).

Findings show that pregabalin may provide pain relief in this patient population.

• These patients had diabetic and/or five other possible causes of peripheral neuropathy.
• No blinding in the study sample.
• Small sample.
• Few patients had cancer.

The findings support that notion that both pregabalin and gabapentin may provide pain relief in some patients with peripheral neuropathy. The majority of cases were patients with diabetes. Application to patients with cancer is unclear.

The aim of the study was to evaluate the safety and efficacy of pregabalin in the management of chemotherapy-induced neuropathic pain.

Children were medicated with pregabalin twice daily starting at 75 mg per day and titrated upwards by 75 mg daily with doses ranging from 150–300 mg for eight weeks. No patient was receiving chemotherapy at the time of pregabalin administration. Patients were evaluated prior to treatment and at weeks 2, 4, 6, and 8 of treatment using a visual analog scale. Patients were asked about side effects.

• The total sample size was 28 (19 females, 11 males).
• Age ranged from 10–17 years; mean age was 13.5 years.
• The participants had been diagnosed with childhood solid tumors and leukemia.
• The participants had been treated with platinum and/or vinca alkaloids and developed peripheral neuropathy.
• No other drug was used for neuropathic pain.

The study was conducted at a single outpatient setting in the Czech Republic.

The study had a prospective trial design.

Visual analog scale

The mean visual analog scale score decreased by 59% from baseline during eight weeks of pregabalin with statistically significant improvement in pain symptoms (p < 0.001). A marked pain relief was noted in 14, moderate pain relief in 10, mild pain relief in two, and no pain relief in two patients. Adverse effects were mild or moderate.

Pregabalin appears to be safe and effective in treating pediatric patients with cancer suffering from chemotherapy-induced peripheral neuropathy. Pregabalin has mild to moderate adverse effects.

• The sample size was small (less than 30).
• The study lacked a comparison or control group.
• Measurement of pain was conducted with one scale.
• The patient population age limits the ability to generalize findings to the adult cancer population.

Pregabalin has been shown to be effective in relieving pain from chemotherapy in pediatric patients; however, pregabalin is expensive and a controlled drug. Preagabalin has mild to moderate side effects and was tolerated without major complications.