Abstract
Pancreatic cancer is a malignant neoplasm of the pancreas. Early detection is difficult, as patients seldom exhibit disease-specific symptoms at the early stages of pancreatic cancer, resulting in a late diagnosis. The majority of pancreatic cancers are, upon diagnosis, advanced and unresectable. Pancreatic cancer has the lowest survival rate amongst all malignancies, with a 5-year survival rate of less than 5%. The current treatment for pancreatic cancer is very limited and ineffective. Palliative chemotherapy is usually administered in an attempt to prolong survivability and to improve the quality of life. Gemcitabine and a combination of gemcitabine and erlotinib are the only FDA approved standard therapies for unresectable pancreatic cancer. Several gemcitabine-based combination therapies have been studied for the treatment of pancreatic cancer, none of which have shown any significant benefit over gemcitabine monotherapy. There is no established second-line treatment. In an effort to improve the efficacy and reduce the side-effects of chemotherapy, targeted therapy has become one of the main approaches. Erlotinib, a tyrosine kinase inhibitor, is the only FDA approved targeted therapy when used with gemcitabine for advanced pancreatic cancer with a limited increase in survival. Herbal medicine has been commonly used by cancer patients in Asia to ameliorate the disease. Several clinical studies have shown PHY906, an herbal formulation that has been used for centuries to treat gastrointestinal ailments, to have high potential in treating advanced stages of various cancers. PHY906 is an example of a polychemical that affects not just one, but many targets. This multi-pronged approach brings a new horizon for cancer therapy.
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References
Abe Y, Hashimoto S, Horie T (1999) Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacol Res 39:41–47
Adis R and D Profiles (2003) EGb 761: Ginkgo biloba extract, Ginkor. Drugs R D 4:188–193
Berlin JD, Catalano P, Thomas JP et al (2002) Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group trial E2297. J Clin Oncol 20:3270–3275
Burris HA III, Moore MJ, Andersen J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413
Carmichael J, Fink U, Russell RC et al (1996) Phase II study of gemcitabine in patients with advanced pancreatic cancer. Br J Cancer 73:101–105
Carter SK, Comis RL (1975) The integration of chemotherapy into a combined modality approach for cancer treatment. VI. Pancreatic adenocarcinoma. Cancer Treat Rev 2:193–214
Casper ES, Green MR, Kelsen DP et al (1994) Phase II trial of gemcitabine (2,2’-difluorodeoxycytidine) in patients with adenocarcinoma of the pancreas. Invest New Drugs 12:29–34
Chattopadhyay I, Biswas K, Bandyopadhyay U et al (2004) Turmeric and curcumin: biological actions and medicinal applications. Curr Sci 87:44–50
Chauffert B, Mornex F, Bonnetain F et al (2008) Phase III trial comparing intensive induction chemoradiotherapy (60Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Ann Oncol 19:1592–1599
Cheverton P, Friess H, Andras C et al (2004) Phase III results of exatecan (DX-8951f) versus gemcitabine (Gem) in chemotherapy-naïve patients with advanced pancreatic cancer (APC). J Clin Oncol 22:4005
Cohen SJ, Dobelbower R Jr, Lipsitz S et al (2005) A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282. Int J Radiat Oncol Biol Phys 62:1345–1350
Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825
Cullinan SA, Moertel CG, Fleming TR et al (1985) A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA 253:2061–2067
Cunningham D, Chau I, Stocken C et al (2005) Phase III randomized comparison of gemcitabine (GEM) versus gemcitabine plus capecitabine (GEM-CAP) in patients with advanced pancreatic cancer. Eur J Cancer Suppl 3:12. Abstract PS11
Dhillon N, Aggarwal BB, Newman RA et al (2008) Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 14:4491
Duvoix A, Blasius R, Delhalle S et al (2005) Chemopreventive and therapeutic effects of curcumin. Cancer Lett 223:181–190
Ebrahimi B, Tucker SL, Li D et al (2004) Cytokines in pancreatic carcinoma: correlation with phenotypic characteristics and prognosis. Cancer 101:2727–2736
Farrell MP, Kummar S (2003) Phase I/IIA randomized study of PHY906, a novel herbal agent, as a modulator of chemotherapy in patients with advanced colorectal cancer. Clin Colorectal Cancer 2:253–256
Hauns B, Häring B, Köhler S et al (1999) Phase II study with 5-fluorouracil and ginkgo biloba extract (GBE 761 ONC) in patients with pancreatic cancer. Arzneimittelforschung 49:1030–1034
Heinemann V, Quietzsch D, Gieseler F et al (2006) Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol 24:3946–3952
Herrmann R, Bodoky G, Ruhstaller T et al (2007) Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer: a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group. J Clin Oncol 25:2212–2217
Jemal A, Siegel R, Ward E (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249
Kalser MH, Ellenberg SS (1985) Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120:899–903
Kanai M, Yoshimura K, Asada M et al (2010) A phase I/II study of gemcitabine-based chemotherapy plus curcumin for patients with gemcitabine-resistant pancreatic cancer. Cancer Chemother Pharmacol. Published by Springer
Kindler HL, Niedzwiecki D, Hollis D et al (2007) A double-blind, placebo-controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients (pts) with advanced pancreatic cancer (PC): a preliminary analysis od Cancer and Leukemia Group B (CALGB) 80303. ASCO gastrointestinal cancers symposium. Abstract no: 108
Klinkenbijl JH, Jeekel J, Sahmoud T et al (1999) Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230:776–782
Koshy MC, Landry JC, Cavanaugh SX et al (2005) A challenge to the therapeutic nihilism of ESPAC-1. Int J Radiat Oncol Biol Phys 61:965–966
Kummar S, Copur MS, Rose M et al (2011) A phase I study of the Chinese herbal medicine PHY906 as a modulator of irinotecan-based chemotherapy in patients with advanced colorectal cancer. Clin Colorectal Cancer 10:85–96
Lam W, Bussom S, Guan F et al (2010) The four-herb Chinese medicine PHY906 reduces chemotherapy-induced gastrointestinal toxicity. Sci Transl Med 2:45ra59
Le Bars PL, Katz MM, Berman N et al (1997) A placebo-controlled double-blind, randomized trial of an extract of Gingo biloba for dementia. JAMA 278:1327–1332, 22–29
Lersch C, van Cutsem E, Amado R et al (2001) Randomized phase II study of SCH 66336 and gemcitabine in the treatment of metastatic adenocarcinoma of the pancreas. Proc Am Soc Clin Oncol 20. Abstract no: 608
Li J, Merl MY, Saif MW (2010) Any second-line therapy for advanced pancreatic cancer? Highlights from the “2010 ASCO Gastrointestinal Cancers Symposium”. JOP 11:151–153
Liu LM (2008) On pathological mechanism and disease-based treatment of pancreatic cancer in traditional Chinese medicine. Zhong Xi Yi Jie He Xue Bao 6:1297–1299
Liu LM, Wu LC, Lin SY et al (2003) Therapeutic evaluation on advanced pancreatic cancer treated by integrative Chinese and Western medicine: clinical analysis of 56 cases. Chin J Integr Med 9:39–43
Liu SH, Jiang Z, Liddil J, Hu K, Gullen EA, Cheng YC (2000) Prevention of CPT-11 induced toxicity by a Chinese medicinal formulation, PHY-906. Proc Am Assoc Cancer Res 41:410, 2608
Loehrer PJ, Powell ME, Cardenes HR et al (2008) A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer: E4201. J Clin Oncol 26(15 Suppl). Abstract 4506
Louvet C, Labianca R, Hammel P et al (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23:3509–3516
Moertel CG, Frytak S, Hahn RG et al (1981) Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48:1705–1710
Moore MJ, Hamm J, Dancey J et al (2003) Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12–9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 21:3296–3302
Moore MJ, Goldstein D, Hamm J et al (2005) Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). J Clin Oncol 23(16S part I). Abstract no: 1
Mu DQ, Peng SY, Wang GF (2004) Risk factors influencing recurrence following resection of pancreatic head cancer. World J Gastroenterol 10:906–909
Neoptolemos JP, Stocken DD, Friess H et al (2004) A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350:1200–1210
Neoptolemos J, Büchler M, Stocken DD et al (2009) A multicenter, international, open-label, randomized, controlled phase III trial of adjuvant 5-fluorouracil/folinic acid (5-FU/FA) versus gemcitabine (GEM) in patients with resected pancreatic ductal adenocarcinoma. J Clin Oncol 27(18 Suppl). Abstract LBA4505
Oettle H, Post S, Neuhaus P et al (2007) Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 297:267–277
Ouyang HQ, Liu LM, Chen Z et al (2010) Effects of Qingyi Huaji decoction on serum levels of interleukin-6, interleukin-8 and tumor necrosis factor-alpha in nude mice bearing pancreatic tumors. Zhong Xi Yi Jie He Xue Bao 8:655–661
Philip PA, Benedetti J, Fenoglio-Preiser C et al (2007) Phase III study of gemcitabine (G) plus cetuximab (C) versus gemcitabine in patients (pts) with locally advanced or metastatic pancreatic adenocarcinoma (PC): SWOG S0205 study. J Clin Oncol 25(18S). Abstract LBA4509
Pugazhenthi S, Akhov L, Selvaraj G et al (2007) Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells. Am J Physiol Endocrinol Metab 293:E645–E655
Ray B, Lahiri DK (2009) Neuroinflammation in Alzheimer’s disease: different molecular targets and potential therapeutic agents including curcumin. Curr Opin Pharmacol 4:434–444
Regine WF, Winter KA, Abrams RA et al (2008) Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA 299:1019–1026
Reiss H, Helm A, Niedergethmann M et al (2005) A randomized, prospective, multicenter, phase III trial of gemcitabine, 5-fluorouracil (5-FU), folinic acid vs. gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 23(16S). Abstract LBA4009
Rocha Lima CM, Green MR, Rotche R et al (2004) Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 22:3776–3783
Rubin J, Gallagher JG, Schroeder G et al (1996) Phase II trials of 5-fluorouracil and leucovorin in patients with metastatic gastric or pancreatic carcinoma. Cancer 78:1888–1891
Saif MW (2008) Is there a role for herbal medicine in the treatment of pancreatic cancer? Highlights from the “44th ASCO Annual Meeting”. JOP 9:403–407
Saif M, Li J, Lamb L et al (2009) A phase II study of capecitabine (CAP) plus PHY906 in patients (pts) with advanced pancreatic cancer (APC). J Clin Oncol 27:15S, e15508
Saif M, Li J, Lamb L et al (2010a) Phase II study of PHY906 plus capecitabine (CAP) in pts with gemcitabine-refractory pancreatic cancer (PC) and measurement of cytokines. J Clin Oncol 28(S). Abstract e14540
Saif MW, Lansigan F, Ruta S et al (2010b) Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies. Phytomedicine 17:161–169
Shen YH, Liu LM, Chen Z et al (2006) Study on Chinese medicine combined with chemotherapy for treatment of 32 cases of advanced pancreatic cancer[J]. Zhong Yi Za Zhi 47:115–117
Shen YH, Liu LM, Meng ZQ et al (2009) Survival analysis on 64 cases of advanced pancreatic cancer treated by integrated Western and traditional Chinese medicine mainly with Qingyi Huaji formula[J]. Zhong Yi Za Zhi 50:39–42
Shibata K, Matsumoto T, Yada K et al (2005) Factors predicting recurrence after resection of pancreatic ductal carcinoma. Pancreas 31:69–73
Shukla PK, Khanna VK, Khan MY et al (2003) Protective effect of curcumin against lead neurotoxicity in rat. Hum Exp Toxicol 22:653–658
Tilton R, Paiva AA, Guan JQ et al (2010) A comprehensive platform for quality control of botanical drugs (PhytomicsQC): a case study of Huangqin Tang (HQT) and PHY906. Chin Med 5:30
Wang Z, Zhang Y, Banerjee S et al (2006) Notch-1 down-regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells. Cancer 106:2503–2513
Yen Y, So S, Rose M et al (2009) Phase I/II study of PHY906/capecitabine in advanced hepatocellular carcinoma. Anticancer Res 29:4083–4092
Zhang Q, Wang XM, Chi HC (2007) Effects of Guben Yiliu II combined with arterial perfusion with chemotherapeutic agent in treating advanced pancreatic cancer. Zhongguo Zhong Xi Yi Jie He Za Zhi 27:400–403
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Liu, SH., Saif, M.W. (2012). Evidence-based Anticancer Materia Medica for Pancreatic Cancer. In: Cho, W. (eds) Materia Medica for Various Cancers. Evidence-based Anticancer Complementary and Alternative Medicine, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-1983-5_11
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DOI: https://doi.org/10.1007/978-94-007-1983-5_11
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