The Role of Pharmacoethnicity in the Development of Cytotoxic and Molecular Targeted Drugs in Oncology

다국어 초록 (Multilingual Abstract)

The effective and toxic ranges of anticancer drugs are very narrow and, in some cases, inverted. Thus determination of the most appropriate dosage and schedule of administration is crucial for optimal chemotherapy. In common arm trials conducted in Japan and by Southwest Oncology Group (SWOG) that used the same doses and schedules for the administration of carboplatin plus paclitaxel, the frequency of hematological toxicity was significantly higher in the Japanese trials than in the SWOG trial, despite demonstrating similar response rates. The frequency of epidermal growth factor receptor (EGFR) mutations in tumors was significantly higher among East Asian populations, and these populations are also reported to demonstrate a higher response rates to epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs). The prevalence of interstitial lung disease induced by treatment with EGFR-TKIs has been shown to be quite high in the Japanese population. Clinical trials of cetuximab against non-small cell lung cancer and of bevacizumab against stomach cancer have shown that these agents are only active in Caucasians. In a trial examining the use of sorafenib after transarterial chemoembolization in Korean and Japanese patients with advanced hepatocellular carcinoma, the compliance and dose intensity of the drug were quite low compared with other trials. Although not only identified pharmacogenomics differences but also differences in social environment,and regional medical care, including pharmacoeconomics strongly influence ethnic differences in treatment response, further identification and understanding of the pharmacogenomics underlying ethnic differences will be essential to timely and reliable global development of new anticancer drugs.

참고문헌 (Reference)

1 Ranson M, "ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial" 20 : 2240-2250, 2002

2 Kubota K, "Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study" 9 : 1135-1142, 2008

3 Lecomte T, "Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy" 10 : 5880-5888, 2004

4 Nishina T, "The effect of CYP2C19 polymorphism on the tolerability of ARQ 197: results from phase I trial in Japanese patients with metastatic solid tumors" 29 : 2516-, 2011

5 Herbst RS, "TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer" 23 : 5892-5899, 2005

6 Llovet JM, "Sorafenib in advanced hepatocellular carcinoma" 359 : 378-390, 2008

7 Herbst RS, "Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial" 20 : 3815-3825, 2002

8 Schwab M, "Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group" 26 : 2131-2138, 2008

9 Takano T, "Risk factors for interstitial lung disease and predictive factors for tumor response in patients with advanced non-small cell lung cancer treated with gefitinib" 45 : 93-104, 2004

10 Ohe Y, "Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan" 18 : 317-323, 2007

11 Liu V, "Pulmonary toxicity associated with erlotinib" 132 : 1042-1044, 2007

12 Rossi SE, "Pulmonary drug toxicity: radiologic and pathologic manifestations" 20 : 1245-1259, 2000

13 Ando M, "Predictive factors for interstitial lung disease, antitumor response, and survival in non-small-cell lung cancer patients treated with gefitinib" 24 : 2549-2556, 2006

14 Williamson SK, "Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003" 23 : 9097-9104, 2005

15 Lara PN Jr, "Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124" 27 : 2530-2535, 2009

16 Kudo M, "Phase III study of sorafenib after transarterial chemoembolisation in Japanese and Korean patients with unresectable hepatocellular carcinoma" 47 : 2117-2127, 2011

17 Gatzemeier U, "Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial" 25 : 1545-1552, 2007

18 Takahashi T, "Phase II study of erlotinib in Japanese patients with advanced non-small cell lung cancer" 30 : 557-563, 2010

19 Baselga J, "Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types" 20 : 4292-4302, 2002

20 Nakagawa K, "Phase I pharmacokinetic trial of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (‘Iressa’, ZD1839) in Japanese patients with solid malignant tumors" 14 : 922-930, 2003

21 Huang RS, "Pharmacogenetics and pharmacogenomics of anticancer agents" 59 : 42-55, 2009

22 Lal S, "Novel SLC22A16 polymorphisms and influence on doxorubicin pharmacokinetics in Asian breast cancer patients" 8 : 567-575, 2007

23 Mitsudomi T, "Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence" 23 : 2513-2520, 2005

24 Fukuoka M, "Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial)" 21 : 2237-2246, 2003

25 Yang JCH, "LUX-Lung3: a randomized, open-label phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. ASCO 2012" 30 : 2012

26 Gandara DR, "Japanese-US common-arm analysis of paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a model for assessing population-related pharmacogenomics" 27 : 3540-3546, 2009

27 Huang SM, "Is this the drug or dose for you? Impact and consideration of ethnic factors in global drug development, regulatory review, and clinical practice" 84 : 287-294, 2008

28 Noda K, "Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer" 346 : 85-91, 2002

29 Minami H, "Irinotecan pharmacokinetics/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28" 17 : 497-504, 2007

30 Kudoh S, "Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study" 177 : 1348-1357, 2008

31 Jones SJ, "ILD during erlotinib and gefitinib treatment in Japanese patients with non-small cell lung cancer" 5 : 1877-1878, 2010

32 Mitsudomi T, "Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial" 11 : 121-128, 2010

33 Thatcher N, "Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)" 366 : 1527-1537, 2005

34 Maemondo M, "Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR" 362 : 2380-2388, 2010

35 Mok TS, "Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma" 361 : 947-957, 2009

36 Herbst RS, "Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2" 22 : 785-794, 2004

37 Giaccone G, "Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1" 22 : 777-784, 2004

38 Lind JS, "Fatal interstitial lung disease after erlotinib for non-small cell lung cancer" 3 : 1050-1053, 2008

39 Marsh S, "Ethnic variation in the thymidylate synthase enhancer region polymorphism among Caucasian and Asian populations" 58 : 310-312, 1999

40 Soo RA, "Ethnic differences in survival outcome in patients with advanced stage non-small cell lung cancer: results of a meta-analysis of randomized controlled trials" 6 : 1030-1038, 2011

41 Rosell R, "Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial" 13 : 239-246, 2012

42 Zhou C, "Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study" 12 : 735-742, 2011

43 Shepherd FA, "Erlotinib in previously treated non-small-cell lung cancer" 353 : 123-132, 2005

44 Takano T, "Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer" 23 : 6829-6837, 2005

45 Kris MG, "Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial" 290 : 2149-2158, 2003

46 Kishi K, "Efficacy of gefitinib in a patient with lung cancer associated with idiopathic pulmonary fibrosis" 1 : 733-734, 2006

47 Cheng AL, "Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial" 10 : 25-34, 2009

48 Renbarger JL, "Effect of race on vincristine-associated neurotoxicity in pediatric acute lymphoblastic leukemia patients" 50 : 769-771, 2008

49 Paez JG, "EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy" 304 : 1497-1500, 2004

50 Toyooka S, "EGFR mutation and response of lung cancer to gefitinib" 352 : 2136-, 2005

51 Innocenti F, "Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics" 2604-2614, 2009

52 Lara PN Jr, "Common arm comparative outcomes analysis of phase 3 trials of cisplatin + irinotecan versus cisplatin + etoposide in extensive stage small cell lung cancer: final patient-level results from Japan Clinical Oncology Group 9511 and Southwest Oncology Group 0124" 116 : 5710-5715, 2010

53 Pirker R, "Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial" 373 : 1525-1531, 2009

54 Weinstein IB, "Cancer. Addiction to oncogenes--the Achilles heal of cancer" 297 : 63-64, 2002

55 O’Donnell PH, "Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy" 15 : 4806-4814, 2009

56 Ohtsu A, "Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study" 29 : 3968-3976, 2011

57 Petros WP, "Associations between drug metabolism genotype, chemotherapy pharmacokinetics, and overall survival in patients with breast cancer" 23 : 6117-6125, 2005

58 Lynch TJ, "Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib" 350 : 2129-2139, 2004