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].