RESUMEN

PURPOSE: Hangeshashinto (TJ-14), a Kampo medicine comprising seven types of herbs, has been used in Japan to alleviate the side effects associated with anticancer drug treatments. However, the pharmacological effects of this medicine currently remain unclear. The present study aimed to demonstrate the efficacy of TJ-14 against anticancer drug-induced stomatitis, the pain associated with which may have a negative impact on mastication and swallowing. METHODS: Mucositis was induced in Sprague-Dawley rats by cancer chemotherapy. Changes in body weight, stomatitis grades, histopathological scores, and oral bacterial counts were examined among TJ-14-treated, saline-treated, and Control (no treatment) rats. In vitro studies, including cell proliferation and wound healing assays, using epidermal keratinocyte and fibroblast cell lines were conducted. RESULTS: The local application of TJ-14 exerted strong antibacterial effects and attenuated oral chemotherapy-induced stomatitis in rats. TJ-14 also increased the viability and invasion of epidermal keratinocytes and fibroblasts. CONCLUSION: The present results demonstrated the potential of TJ-14 to attenuate chemotherapy-induced stomatitis.

RESUMEN

The purpose of this multi-institutional Phase II trial study was to prospectively investigate the efficacy of the herbal medicine TJ-14 for acute radiation-induced enteritis (ARE). TJ-14 was administered orally as a first-line treatment for ARE. The primary end point was efficacy at 1 week. The secondary end points were: (i) the efficacy of TJ-14 at 2 and 3 weeks after its administration, (ii) the quality of life score (FACT-G) at 1, 2 and 3 weeks after its administration, and (iii) adverse events. If the efficacy of TJ-14 was observed in eight patients or fewer, its efficacy was rejected. Results: Forty patients receiving pelvic radiotherapy were enrolled. Of these, 22 developed ARE and received TJ-14. Among these, 19 had cervical cancer and 9 received chemoradiotherapy. TJ-14 efficacy was shown in 19 out of the 22 patients (86%). Stool frequency per day at 1 week significantly decreased (mean ± SD: 4.9 ± 2.1 vs 3.7 ± 1.9, P = 0.02). This effect continued at 2 (2.2 ± 1.4, P = 0.004) and 3 weeks (2.1 ± 0.9, P = 0.05). Thirteen out of the 22 patients (59%) continued TJ-14 until the end of radiotherapy. FACT-G score deterioration was not observed after the administration of TJ-14. Grade 1 hypokalemia was observed in 4 patients, and Grade 1 constipation in 3. We concluded that TJ-14 is sufficiently promising to be examined in a Phase III trial. A randomized controlled trial is currently being planned.

Asunto(s)

Medicamentos Herbarios Chinos/uso terapéutico , Enteritis/tratamiento farmacológico , Enteritis/etiología , Traumatismos por Radiación/complicaciones , Traumatismos por Radiación/tratamiento farmacológico , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento

RESUMEN

Irinotecan hydrochloride (CPT-11) is used to treat a wide spectrum of malignant tumors. Hangeshashin-to (Japanese herbal medicine TJ-14) is reportedly effective in preventing and controlling diarrhea associated with CPT-11. However, the effect of TJ-14 on tolerability of chemotherapy with CPT-11 has not been fully investigated. We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify patients who had received CPT-11 on their first admission with and without TJ-14. Patients who did receive TJ-14 (N = 7092) received CPT-11 more often and in larger doses than those who did not receive TJ-14 (N = 82,019). The incidence rate ratio of CPT-11 administration was 1.34 for frequency (95% confidence interval [CI], 1.31⁻1.38; p < 0.001), and 1.16 for total dose (95% CI, 1.14⁻1.19; p < 0.001) according to stabilized inverse probability treatment weighting using propensity scores. Instrumental variable analysis showed similar trends. In-hospital mortality was significantly lower in patients who received TJ-14 than in those who did not. Odds ratios of in-hospital death in patients receiving TJ-14 was 0.81 (95% CI, 0.71⁻0.93; p = 0.002) according to stabilized inverse probability treatment weighting using propensity scores and 0.42 (95% CI, 0.22⁻0.81; p = 0.009) according to instrumental variable analysis. Our findings indicate that TJ-14 improve the tolerability of CPT-11.

RESUMEN

BACKGROUND: The optimal treatment of chemotherapy-induced oral mucositis is not well established. A recent study showed that hangeshashinto (TJ-14) might be useful for periodontal disease via downregulating pro-inflammatory prostaglandins in the cyclooxygenase pathway in human. Our study aimed to determine whether TJ-14 is effective in the management of chemotherapy-induced oral mucositis. METHODS: Fourteen patients afflicted with chemotherapy-induced oral mucositis during mFOLFOX6 or FOLFIRI treatment for metastasis of advanced colorectal cancer were randomly assigned to topical TJ-14 treatment thrice daily for 7 days. Patients prepared a 50 ml solution with 2.5 g of TJ-14 dissolved in tap water and rinsed their oral mucosa for more than 5 seconds and then expectorated it. TJ-14 was also topically applied with a cotton pellet on the mucosal lesions. The severity of oral mucositis was evaluated using the Common Terminology Criteria for Adverse Events version 4 before and after one-week TJ-14 treatment. RESULTS: After the one-week topical treatment with TJ-14, thirteen of the fourteen patients (92.8 %) showed improvements in oral mucositis, with significantly decreased mean CTCAE grades (P = 0.0012). Compared to baseline, none of the patients' CTCAE grades worsened. The compliance of TJ-14-treatment was good and side effects from TJ-14 were not observed. CONCLUSIONS: Topical application of TJ-14 may have therapeutic effects in patients with chemotherapy-induced oral mucositis via downregulation of pro-inflammatory prostaglandins. A prospective, randomized, controlled, double-blind studies are necessary to confirm the findings of this open-label, pilot study.