2.2. Study Design:
This was a randomized, double-blind, placebo-controlled study. Patients treated with chemotherapy regimens consist of taxanes, platinum derivatives, vincristine or thalidomide and experienced symptoms of peripheral neuropathy were screened for enrollment. Block randomization with the size of four in each block was used to allocate patients in treatment or control arms. Each patient was assigned a computer-based unique five-digit randomization code. The codes was held by a third party and handed over for statistical analyses after the complement of data collection. Both Silymarin and placebo were manufactured by an authorized pharmaceutical company (Goldaru, Isfahan, Iran). The placebo and silymarin were indistinguishable in size, weight, and their appearance. The treatment regimens was carried out according to the following scheme: Intervention group received 140 mg of the silymarin in two daily doses with 300 mg/day Gabapentin as a usual treatment of peripheral neuropathy, while the comparison group received 300 mg/day of Gabapentin and placebo (filled by microcrystalline cellulose). The schedule of administration of placebo was equal to silymarin (twice daily). Duration of trial was 3 months. Patients were evaluated at baseline and 3 months after entering the study.
The primary objective was to evaluate the efficacy of the drug. Demographic and clinical characteristics of patients were recorded. Possible side effects of silymarin were recorded.
The CTCAE criterion (Common Terminology Criteria for Adverse Events) was used to assess the severity of neuropathy [17]. The grading of neuropathy was carried out based on the presence of paresthesia, peripheral motor neuropathy or peripheral sensory neuropathy and the level of limiting impact on activity of daily living (ADL) or self-care ADL. Improvement of neuropathy was defined as the reduction of at least one neuropathic score.
According to this criterion, a score of zero is equivalent to the absence of neuropathy, a score of 1 is equivalent to mild neuropathy, a score of 2 is equivalent to moderate neuropathy which limits instrumental ADL, a score of 3 is equivalent to severe neuropathy correspond which limits the self-care ADL, a score of 4 is equivalent to life-threatening neuropathy.
The visual analogue scale (VAS) was also used to assess the severity of patients’ pain. The visual analogue scale was rated from 0 (no pain) to 10 (the most severe pain the patient has ever experienced). The EORTC-QLQ-C30 (European Organization for Research and Treatment of Cancer - quality of life - questionnaires ) criterion was used to assess the improvement of patients’ quality of life [18].