Cobrotoxin produces intense
analgesia but it has an onset of response of 1-3 h which hampers its clinical use in
cancer pain. Recently, a compound
analgesic formulation combining
cobrotoxin,
tramadol hydrochloride and
ibuprofen (Compound Keluoqu, CKLQ) has become available in China. The aim of this study was to evaluate the clinical efficacy of CKLQ for moderate to severe
cancer pain. A consecutive series of patients with chronic moderate to severe
cancer pain was enrolled into two multicenter trials. Of the 230 eligible patients, 119 were assigned to a randomized, double-blind, cross-over study, while 111 entered an open-label study. They were all of Han-China nationality and had a mean age of 52.0 and 55.4 years and a mean
body weight of 55.6 and 52.9 kg, respectively. A total of 11 patients discontinued the study, 6 (54.5%) because of insufficient
pain relief and 5 due to the occurrence of adverse events. In the cross-over study, 59 patients were randomized to receive a CKLQ package with 2 CKLQ
tablets (each containing 0.16 mg
cobrotoxin, 25 mg
tramadol hydrochloride and 50 mg
ibuprofen) and 2 placebo capsules, a placebo package with 2 placebo
tablets and 2 placebo capsules, and an active control package with 2
tramadol hydrochloride capsules (each containing 50 mg
tramadol hydrochloride) and 2 placebo
tablets (arm A), and 60 to receive a
tramadol hydrochloride package, a placebo package and a CKLQ package (arm B), sequentially and only once. Patients in the open-label study only received CKLQ and were given the option to continue for up to 7 days as long as they had satisfactory
pain relief.
Pain response was classified as CR, PR and NC. CR was defined as 100%
pain relief, with a
pain score of 0 on a 0-10 VAS. PR was defined as decreased to mild
pain, with a
pain score of no more than 4 on a 0-10 VAS. NC was defined as
pain that either remained unchanged or that was reduced from severe to moderate at baseline, with a VAS
pain score of more than 4
after treatment. One hundred and eight patients completed the cross-over study with all the three
drug units. The overall rate of
pain relief was 93/111 (83.7%) for CKLQ, 75/110 (68.2%) for
tramadol hydrochloride (P=0.011) and 39/111 (35.1%) for placebo (P<0.001). The mean duration of
pain relief with CKLQ was significantly longer than that of the other two agents (P<0.001). Of the 35 patients who did not respond to
tramadol hydrochloride, 27 (77.1%) responded to CKLQ, while of the 18 who did not respond to CKLQ, 8 (55.6%) achieved satisfactory
pain control with
tramadol hydrochloride. In the open-label study, the overall relief rate of a single-dose of CKLQ was 99/111 (89.2%). A reduction in the percentage of complete relief, an increase in that of PR and a significant decrease in duration of relief were observed after continuous treatment with at least 10 doses of CKLQ. The frequency of adverse events for CKLQ was similar to that of
tramadol hydrochloride. The results of the randomized, double-blind, cross-over study and the open-label study of CKLQ in
cancer patients with chronic moderate to severe
cancer pain suggest that the CKLQ may be valuable for the treatment of chronic moderate to severe
cancer pain. However, the tolerance of CKLQ remains to be further defined.