L/O/G/O 癌症免疫療法 KRESTIN 杏昌醫藥科技股份有限公司
唯一醫藥級雲芝 Krestin (Polysaccharide K, PSK) 克速鎮 2
標竿臨床試驗參考期刊 : Gastric Cancer 臨床試驗 : 1. Efficacy of Immunochemotherapy as Adjuvant Treatment after Curative Resection of Gastric Cancer Lancet 343: 1122-1126, 1994 2. Effcacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer Cancer Immunol Immunother (2007) 56:905 911 Colorectal Cancer 臨床試驗 : 1. Adjuvant Immunochemotherapy with Oral Tegafur/Uracil Plus PSK in Patients with Stage II or III Colorectal Cancer: A Randomised Controlled Study British Journal of Cancer, 90: 1003-1010 (2004)
Krestin, PSK 標竿臨床試驗
Efficacy of Immunochemotherapy as Adjuvant Treatment after Curative Resection of Gastric Cancer Hiroaki Nakazato, Akihiko Koike, Shigetoyo Saji, Nobuya Ogawa, Junichi Sakamoto for the Study Group of Immunochemotherapy with PSK for Gastric Cancer Lancet 343: 1122-1126, 1994
Treatment Schedule PSK + 5-FU group (n=124) 1 2 3 4 5 6 10 (Course) MMC (i.v.) 6 mg/m 2 1 2 10 18 26 34 42 82 (Weeks) Op Randomization PSK 3 g/day 5-FU 150 mg/day 5-FU group (n=129) Rest MMC (i.v.) 6 mg/m 2 Op 1 2 10 18 26 34 42 82 Randomization (Weeks) Nakazato H et al Lancet 343: 1122-1126, 1994
Overall Survival 整體存活率提高 13% 100 90 80 73.0% Survival Rate (%) 70 60 50 40 30 20 10 0 5-FU 150mg/day(po)+PSK 3g/day(po) (n=124) 5-FU 150mg/day(po) (n=129) Follow-Up (Month) 60.0% Log-rank p=0.044 0 12 24 36 48 60 72 84 Nakazato H et al Lancet 343: 1122-1126, 1994
Disease-Free Survival 無疾病存活率提高 11% Disease-Free Survival Rate (%) 100 90 80 70 60 50 40 30 20 10 0 5-FU 150mg/day(po)+PSK 3g/day(po) (n=124) 5-FU 150mg/day(po) (n=129) 0 12 24 36 48 60 72 84 Follow-Up (Month) 70.7% 59.4% Log-rank p=0.047 Nakazato H et al Lancet 343: 1122-1126, 1994
Meta-analysis 結果顯示 : Krestin 能顯著改善接受根治性切除的胃癌病患的存活率 Survival HRs and 95% CIs based on the three trials with quality scores of A +++ and A ++. Cancer Immunol Immunother (2007) 56:905 911
Adjuvant Immunochemotherapy with Oral Tegafur/Uracil Plus PSK in Patients with Stage II or III Colorectal Cancer: A Randomised Controlled Study Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, Nakamura S, Kakinuma S, Iwazaki S, Ishikawa H, Kawate S, Nakajima T, Morishita Y Department of Surgery, Gunma University, Graduate School of Medicine Gunma Oncology Study Group (GOSG-C) British Journal of Cancer, 90: 1003-1010 (2004)
Disease-Free Survival (5-Year) of All Patients Disease-free survival (%) 100 90 80 70 60 50 40 30 20 10 0 73.0% 58.8% UFT 300mg/day(po) +PSK 3g/day(po) (n = 137) UFT 300mg/day(po) (n = 68) Log rank : P = 0.016 所有受試者無疾病存活率提高 14.2% 0 1 2 3 4 5 Years after surgery Ohwada S et al. Br J Cancer 90:1003-1010, 2004
100 Overall Survival (5-Year) of All Patients Survival (%) 90 80 70 60 50 40 30 20 10 81.8% 72.1% PSK Group Control Group Logrank; p=0.056 0 0 1 2 3 4 5 Years After Surgery Ohwada S et al Br J Cancer 90: 1003-1010 (2004)
100 Disease-Free Survival (ptnm stage III) Disease-free Survival (%) 90 80 70 60 50 40 30 20 第三期受試者無疾病存活率提高 27.9% 10 0 60.0% 32.1% PSK Group Control Group Log rank: p=0.002 0 1 2 3 4 5 Years After Surgery Ohwada S et al Br J Cancer 90: 1003-1010 (2004)
100 Overall Survival (ptnm stage III) 90 80 74.6% Survival (%) 70 60 50 40 30 20 10 第三期受試者整體存活率提高 28.2% 46.4% PSK Group Control Group Logrank; p=0.003 0 0 1 2 3 4 5 Years After Surgery Ohwada S et al Br J Cancer 90: 1003-1010 (2004)
16 14 12 Recurrence Hazard-Rate Control Group PSK Group Hazard rate (%) 10 8 6 4 2 PSK 可保護前兩年腫瘤復發的危險高峰期 0 0 1 2 3 4 5 Years After Surgery Ohwada S et al Br J Cancer 90: 1003-1010 (2004)
為何 Krestin 可降低化療副作用
PSK 可保護 T 細胞免於化療藥物 S-1 的作用而細胞凋亡 Effect of oral administration of PSK on apoptosis of circulating T cells induced by the anticancer drug S-1 in gastric cancer patients. Oncology. 2008;74:143 9.
PSK Decreased FOLFOX4 Induced Peripheral Neuropathy and Bone Marrow Suppression in Patients with Metastatic Colorectal Cancer Jpn J Cancer Chemother 38(5): 797-801, May 2011
PSK 可降低化療藥物 FOLFOX4 骨髓抑制及周邊神經病變的副作用 Hematology FOLFOX4+PSK FOLFOX4 (Goldberg,RM JCO2004) FOLFOX4 (De Gramont A JCO2000) G1~ G3~ G1~ G3~ G1~ G3~ Neutrophil 48% 24% 81% 53% 70% 42% Platelet 16% 0% 71% 5% 76% 2% Neuropathy FOLFOX4+PSK FOLFOX4 (Goldberg,RM JCO2004) FOLFOX4 (De Gramont A JCO2000) G1~ G3~ G1~ G3~ G1~ G3~ Perpheral neuropathy 56% 0% 82% 19% 68% 18%
The role of Immunotherapy in cancer treatment 10 12 Number of cancer cells 10 10 10 8 10 6 10 4 10 2 0 Surgery? Immune response Chemotherapy Immunotherapy Time after surgery Fujimoto S et al. Jpn J cancer Chemother 17:459,1990 (partially-modified)
Krestin (PSK) 的適應症 衛生署 消化器癌 ( 胃癌 食道癌 結腸 直腸癌 ) 日本厚生省 延長胃癌 ( 術後 ) 及結腸直腸癌 ( 治癒切除手術 ) 合併化學療法患者之存活期 對小細胞肺癌患者, 與化學療法等併用可延長有效期間
健保給付規定 1. 限胃癌病人經手術完全切除後, 且同時接受化學治療者, 並須經事前審查核准後使用 2. 每一個案每半年須重新評估, 用藥期間若有復發情形應即停止使用本品 3. 使用本品至多以一年為限