Efficacy of goshajinkigan for peripheral neurotoxicity of oxaliplatin in patients with advanced or recurrent colorectal cancer.

Peripheral neurotoxicity is the major limiting factor for oxaliplatin therapy. Goshajinkigan (GJG), a traditional Japanese herbal medicine, was recently shown to be effective in protecting against the neurotoxicity of taxanes in Japan. We retrospectively investigated the effect of GJG on peripheral neurotoxicity associated with oxaliplatin therapy. Ninety patients with metastatic colorectal cancer that received FOLFOX4 or modified FOLFOX6 therapy were assigned to receive one of the following adjuncts: oral GJG at 7.5 g day(-1) (Group A, n = 11), intravenous supplementation of calcium gluconate and magnesium sulfate (1 g each before and after FOLFOX) (Group B, n = 14), combined GJG and calcium gluconate and magnesium sulfate therapies (Group C, n = 21), or no concomitant therapy (Group D, n = 44). The incidence of peripheral neurotoxicity was investigated when the cumulative dose of oxaliplatin exceeded 500 mg m(-2). When the cumulative dose of oxaliplatin exceeded 500 mg m(-2), the incidence of neuropathy (all grades) in Groups A-D was 50.0%, 100%, 78.9%, and 91.7%, respectively. It was lowest in the group that received GJG alone. Concomitant administration of GJG reduced the neurotoxicity of oxaliplatin in patients that received chemotherapy for colorectal cancer.

[Survey of oxaliplatin-associated peripheral sensory neuropathy using an interview-based questionnaire in patients with advanced colorectal cancer].

In performing FOLFOX chemotherapy (infusional 5-FU/LV with oxaliplatin) for advanced colorectal cancer, the neurotoxicity of oxaliplatin (L-OHP) is the dose-limiting factor. A retrospective study of 25 consecutive patients, receiving modified FOLFOX6 (mFOLFOX6) for advanced colorectal cancer, was conducted. From March 2006 to February 2008, we investigated the process of development of sensory neuropathy by adverse effect grading and our original interview-based intake about the afflicted regions. Neurotoxicity developed in 21 cases (84%) after 6 courses and the cumulative L-OHP dose was 410 mg/m(2) in median. In 11 cases (52%), it developed from the fingers, while in 8 cases (38%), it occurred from the fingers and toes simultaneously. It developed from the toes or tongue only in one case each. In 6 cases (55%), in which it occurred from the fingers, the symptom aggravated to grade 2 (G2) according to the Neurotoxicity Criteria of DEBIOPHARM (DEBNTC). On the other hand, in cases of coexpression of the fingers and toes, 7 cases (88%) developed G2 neuropathy, among one of whom suffered from grade 3 (G3). The coexistence of diabetes mellitus without neuropathy had no influence on the development of the neurotoxicity in the grading of DEB-NTC. One month after the last mFOLFOX6 therapy, neurotoxicity newly developed in one case, and was aggravated in two cases two months after cessation of the chemotherapy. Therefore, careful observation of the course should be continued even after the end of mFOLFOX6 therapy. Our results suggest that L-OHP neurotoxicity develops on fingers or fingers and toes simultaneously in most cases. And when it occurred on fingers and toes simultaneously, it would aggravate to G2 or G3 during the chemotherapy. The interviewed-based intake about the afflicted region, such as ours, can be used to predict the deterioration of the neurotoxicity.

[A case of neurotoxicity reduced with goshajinkigan in modified FOLFOX6 chemotherapy for advanced colon cancer].

In performing FOLFOX (infusional 5-FU/LV with oxaliplatin) for advanced colorectal cancer, neurotoxicity of oxaliplatin (L-OHP) is the serious dose limiting factor. On the other hand, goshajinkigan is recently considered as an effective agent for the neurotoxicity of taxanes in Japan. We have applied goshajinkigan (TJ 107) for a case of advanced colon cancer with mFOLFOX 6, and experienced a reduction in numbness, the adverse effect of LOHP. A 57-year-old woman with descending colon cancer (H 1, P 3, Stage IV) underwent hemicolectomy D 2, rt.colectomy, bilateral oophorectomy, cholecystectomy and transverse colonostomy. After operation, mFOLFOX 6 was applied. In order to reduce the neurotoxicity of L-OHP, TJ 107 was used together from the third course. The severities of neurotoxicity before and after administration of TJ 107 were grade 2 and 1,respectively. TJ 107 could reduce or prevent the neurotoxicity of L-OHP.

Modulation of the sleep state-dependent P50 midlatency auditory-evoked potential by electric stimulation of acupuncture points.

OBJECTIVE: To determine if the P50 midlatency auditory evoked potential, a sleep state-dependent waveform thought to be generated by the reticular activating system, is modulated after surface stimulation of acupuncture points (ie, electroacupuncture). DESIGN: P50 potential recordings were carried out before, during, and after electroacupuncture. SETTING: A clinical research center. PARTICIPANTS: Eighty healthy subjects ages 25 to 55 were recorded in 7 investigations. INTERVENTIONS: Stimulation of 3 specific acupuncture points (Pericardium 6, Heart 3, Liver 3) was compared with no stimulation or with stimulation of control points (Gall Bladder 34, Large Intestine 11, Small Intestine 3). We compared different frequencies of stimulation (5, 60, 100 Hz), unilateral versus bilateral stimulation, and the effects of repeated episodes of stimulation. MAIN OUTCOME MEASURES: P50 auditory evoked potential latency, amplitude (measure of level of arousal), and habituation (measure of sensory gait) at interstimulus interval of 250 ms. RESULTS: Electroacupuncture at specific points decreased P50 potential amplitude versus electroacupuncture at control points (P=.006) or versus no stimulation (P<.001). The optimal effective frequency was 5 Hz (P<.05 at 5 Hz, P>.05 at 60 and 100 Hz), and unilateral electroacupuncture was not as effective as bilateral electroacupuncture (P=.007). Repeated episodes of bilateral electroacupuncture showed additive effects (P<.05). There were no differences in responsiveness across sexes (P=.79), and electroacupuncture did not affect P50 potential habituation (P>.05). CONCLUSIONS: Electroacupuncture may be effectively used to decrease arousal levels, perhaps as adjunct therapy for disorders of hypervigilance.

Protective effect of pretreatment with low-dose lipopolysaccharide on D-galactosamine-induced acute liver failure.

BACKGROUND AND AIMS: The effect of low-dose lipopolysaccharide (LPS) induced nitric oxide (NO) on liver damage and survival in rats with acute liver failure caused by a lethal dose of D-galactosamine (D-gal) was studied. RESULTS: Ninety percent of control animals died within 4 days after D-gal injection, but pretreatment with low-dose LPS significantly decreased mortality to 5%. There was marked elevation in serum aspartate aminotransferase and alanine aminotransferase levels 24 h after D-gal injection. These aminotransferases were significantly improved in low-dose LPS pretreated rats 24 h after the administration of D-gal. NG-Nitro-L-arginine-methyl ester, but not NG-nitro-D-arginine-methyl ester, reversed this cytoprotection. CONCLUSION: Pretreatment with low-dose LPS prevents experimental liver failure induced by D-gal through activation of endogenous NO synthesis.