Won-Cheol Choi

Rhus verniciflua Stokes against Advanced Cancer: A Perspective from the Korean Integrative Cancer Center

Active anticancer molecules have been searched from natural products; many drugs were developed from either natural products or their derivatives following the conventional pharmaceutical paradigm of drug discovery. However, the advances in the knowledge of cancer biology have led to personalized medicine using molecular-targeted agents which create new paradigm. Clinical benefit is dependent on individual biomarker and overall survival is prolonged through cytostatic rather than cytotoxic effects to cancer cell. Therefore, a different approach is needed from the single lead compound screening model based on cytotoxicity. In our experience, the Rhus verniciflua stoke (RVS) extract traditionally used for cancer treatment is beneficial to some advanced cancer patients though it is herbal extract not single compound, and low cytotoxic in vitro. The standardized RVS extracts action mechanisms as well as clinical outcomes are reviewed here. We hope that these preliminary results would stimulate different investigation in natural products from conventional chemicals.

Impact of Standardized Rhus verniciflua Stokes Extract as Complementary Therapy on Metastatic Colorectal Cancer: A Korean Single-Center Experience

Background. To investigate the clinical feasibility of the standardized Rhus verniciflua Stokes (RVS) extract for the metastatic colorectal cancer (mCRC), experimentally proven to have anticancer activities. Patients and Methods. From July 2006 to November 2007, patients with conventional chemotherapy refractory mCRC were checked. After fulfilling inclusion/exclusion criteria, 36 patients were eligible for the final analysis. Overall survival and adverse events of patients treated with RVS in the aftercare period were determined. Results. On October 21, 2008, a total of 26 patients died while the remaining 10 patients were alive with evidence of disease. The median RVS administration period was 2.7 months (95% confidence interval, 1.9-3.5). The median overall survival for the entire population was 10.9 months (95% confidence interval, 5.6-16.1) and 1-year survival rate was 44.4%, which is compatible with external controls. By survival analysis using Cox proportional hazards model, the performance status and the prior chemotherapy regimen number significantly affected overall survival. Adverse reactions to the RVS treatment were mostly mild and self-limiting. Conclusion. Complementary treatment with the standardized RVS extract might be beneficial for patients with mCRC, since it positively affected overall survival without significant side effects. This study suggests that RVS could be a natural anticancer agent candidate for the treatment of colorectal adenocarcinoma.

Shrinkage of gastric cancer in an elderly patient who received Rhus verniciflua Stokes extract.

BACKGROUND Many studies have suggested that the flavonoids from Rhus verniciflua Stokes (RVS) are anticancer agents, but a few clinical studies have reported on this topic. PATIENT AND METHOD We present here the case of a female patient (82 years old) with an adenocarcinoma of the stomach that was first diagnosed via an abdomen computed tomography (CT) scan and endoscopic biopsy. Any conventional therapy such as surgical resection was not performed because of her advanced age. She wanted to receive alternative care, and so she was exclusively treated with standardized RVS extract. COURSE OF THERAPY AND RESULTS: Daily therapy with 900 mg of orally administered RVS extract was initiated on September 25, 2006. Five (5) months later, the gastroscopy and abdomen CT scan showed a marked decrease in the polypoid mass at the mid body and a slight decrease in the flat elevated lesion at the prepyloric antrum, as compared to tumor sizes on the first gastroscopy and abdomen CT scan. She is alive and doing well at the present time (April 2009). CONCLUSIONS We suggest that RVS extract could be a candidate for a natural agent that induces selective apoptosis and inhibits cell growth in gastric adenocarcinoma.

The efficacy and safety of standardized allergen-removed Rhus verniciflua extract as maintenance therapy after first-line chemotherapy in patients with advanced non-small cell lung cancer.

Chemotherapy improves the survival of patients with advanced non-small cell lung cancer (NSCLC), but tumor progression is often inevitable. Strategies are needed to improve the therapeutic efficacy of chemotherapy. Over recent years, there has been increasing interest in the role of maintenance therapy after first-line chemotherapy. We investigated the efficacy and safety of standardized allergen-removed Rhus verniciflua Stokes extract (aRVS) as maintenance therapy in patients with non-progressive disease following first-line chemotherapy. We reviewed the medical records of 33 patients with advanced NSCLC, who started treatment with aRVS in a state of tumor regression or stable disease after completion of four or six cycles of induction chemotherapy at the Integrative Cancer Center, Kyung Hee University Hospital at Gangdong from June 2006 to April 2012. The primary objective of this study was progression-free survival (PFS) of aRVS as maintenance therapy. Secondary objectives included assessments of disease control rate (DCR), overall survival (OS), and the safety of aRVS treatment. The median PFS was 5.2 months with a 6- and 12-month PFS rate of 40.6% and 12.9%, respectively. The DCR was 93.9% and the median OS was 34.8 months. The overall survival rates at 12, 24, and 36 months were 84.2%, 76.7% and 49.9%, respectively. We observed no hematologic toxicity, nephrotoxicity, or hepatotoxicity during aRVS treatment. In conclusion, maintenance therapy with aRVS for patients with advanced NSCLC is well-tolerated and offers encouraging improved PFS and OS compared with historical controls. Our data provide further evidence that aRVS may be used beyond disease progression in this clinical setting.

Efficacy and Safety of Standardized Allergen-Removed Rhus verniciflua Stokes Extract in Patients with Advanced or Metastatic Pancreatic Cancer: A Korean Single-Center Experience

Background: Pancreatic cancer has the worst prognosis because of poor response to conventional therapy. We investigated the clinical feasibility of the standardized allergen-removed Rhus verniciflua Stokes (aRVS) extract as a potential therapeutic agent for advanced or metastatic pancreatic cancer. Patients and Methods: From July 2006 to June 2010, patients with advanced or metastatic pancreatic adenocarcinoma were checked in our institution. After applying inclusion/exclusion criteria, 42 patients were eligible for the final analysis. Overall survival, clinical benefit and adverse events of these patients treated with aRVS in the aftercare period were determined. Results: In May 2011, 39 patients had died and the remaining 3 patients were alive with evidence of disease. The mean RVS administration period was 3.86 months (95% confidence interval 2.52–5.20). The median overall survival for the entire population was 7.87 months (95% confidence interval 5.14–10.59), and the 1-year survival rate was 26.2%, which is compatible with external controls. Using univariate and multivariate analyses, aRVS treatment including performance status and prognostic index significantly affected overall survival. A clinical benefit response was also shown by aRVS treatment which was not dependent on concurrent chemotherapy. Adverse reactions to aRVS treatment were mostly mild and self-limiting. Conclusions: The standardized aRVS extract might be beneficial for patients with advanced or metastatic pancreatic cancer since it positively affected overall survival and clinical symptoms without significant adverse effects.

Carcinostatic effect of allergen removed Rhus Verniciflua stokes based Traditional Korean Medicine on a patient with lung adenocarcinoma; single case report

Lung cancer is one of the leading causes of cancer mortality and overall treatment outcomes for lung cancer are still to be considered disappointing despite of development of new medical therapeutics on cancer. Cytostatic agents are considered as novel medication in the treatment of cancer though its benefit is most appropriately assessed through survival end points rather than the objective-response end points. We present a case of a lung adenocarcinoma patient who showed tumor lesion in patients two different lung sites. From the day of diagnosis, the tumor lesion stayed with the almost same size with more than 1 year of Allergen-Removed Rhus Verniciflua Stokes (A-RVS) based Traditional Korean Medicine treatment without any western conventional treatment. No significant side effect was noted and the patient maintained good performance status throughout the treatment period. We assume A-RVS may have cytostatic effect on NSCLC patient and our observation justifies further investigation.

Impact of Standardized Allergen-Removed Rhus verniciflua Stokes Extract on Advanced Adenocarcinoma of the Ampulla of Vater: A Case Series

Background. Adenocarcinoma of the ampulla of Vater (AAV) is a rare malignancy that has a better prognosis than other periampullary cancers. However, the standard treatment for patients with relapsed or metastatic AAV has not been established. We investigated the clinical feasibility of standardized allergen-removed Rhus verniciflua stokes (aRVS) extract for advanced or metastatic AAV. Patients and Methods. From July 2006 to April 2011, we retrospectively reviewed all patients with advanced AAV treated with aRVS extract alone. After applying inclusion/exclusion criteria, 12 patients were eligible for the final analysis. We assessed the progression-free survival (PFS) and overall survival (OS) of these patients during the follow-up period. Results. The median aRVS administration period was 147.0 days (range: 72–601 days). The best tumor responses according to Response Evaluation Criteria in Solid Tumors were as follows: two with complete response, two with stable disease, and eight with progressive disease. The median OS was 15.1 months (range: 4.9–25.1 months), and the median PFS was 3.0 months (range: 1.6–11.4 months). Adverse reactions to the aRVS treatment were mostly mild and self-limiting. Conclusions. Prolonged survival was observed in patients with advanced AAV under the treatment of standardized aRVS extract without significant adverse effects.