Oncology in Emerging Markets

Oncology in Emerging Markets W H I T E P A P E R Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 1 www.makrocare.com/mcsmo

C W H I T E P A P E R ancer has been the leading cause of death in economically developed countries and stands second in developing countries. The global burden of cancer continues to thrive mostly due to aging and growth of world population with increasing adoption of behavioral patterns mainly smoking, physical inactivity and adoption of westernized diets, in economically developing countries. According to GLOBOCAN 2008 estimation, there had been 12.7 million cancer cases and 7.6 million deaths from cancer in 2008 only; of which 56% of cases and 64% deaths have occurred in economically developing world. In females, breast cancer remains predominant in diagnosis and death majoring to 23% of total cancer cases and 14% of cancer deaths, whereas lung cancer is in males amounting to 17% of total new cancer cases and 23% of total cancer deaths. In economically developing regions cervical cancer once thought to be prime cause in female cancer deaths has now been overtaken by breast cancer. In addition, in developing countries mortality burden in females is high for lung cancer as is for burden from cervical cancer, with each accounting to 11% of total female cancer deaths. In spite of incidence rates in developing world are half to that of developed world for both sexes; overall cancer mortality is by and large same. The survival rate tends to be poorer in developing countries due to combination of late stage at diagnosis and limited accessibility to timely and standard treatment. 1.0 Risk Factors It has been seen that the associated risk of developing cancer increases with age. In economically developed countries, about 78% of newly diagnosed cancer cases occur at 55 years of age or older, in comparison to 58% in developing countries. This difference can be attributed to age structure of populations. The population of developing countries is younger and has smaller percentage of older people in whom cancer can occur most frequently. Furthermore, increased adoption on use of alcohol, tobacco (for lung cancer), rising incidences of infectious agents including hepatitis B and C virus (liver cancer), human papilloma viruses (cervical and ano-genital cancers), and Helicobacter pylori (stomach cancer), exposure to occupational carcinogens, and the Western nutrition and lifestyle. Figure 1 shows cancer causes in terms of [1, 2] major risk factors and economic development in both developed and developing countries. Fig.1: Proportion of cancer causes by major risk factors and level of Economic Development [2] Source: Cancer Atlas 2006 Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 2

2.0 Epidemiology In 2008, the incidence rate (per 100,000) for all cancers combined was higher in more developed countries as compared to less developed countries for both sexes (Men: 300.1 vs. 160.3 ; Women: 225.5 vs. 138.0). However, mortality rate for all cancers combined was usually same between more and less developed countries, especially among women (87.3 vs. 85.4, respectively). These differences was related to disparity in both type of major cancers and accessibility to early detection and treatment services in more and less developed countries. In developed countries prostate, colorectal and lung cancer rates are 2-5 times elevated than in developing countries, these variations are due to disparate set of risk factors and diagnostic practices implemented. It is similarly true for cancers due to infections (stomach, liver and cervical). In 2008, there were about 12.7 million new cancer cases and 7.6 million deaths (21,000 deaths/day), Among the total death cases it was 2.8 million in economically developed countries and 4.8 million in economically developing regions of the world and this global burden is expected to grow to 21.4 million new cases and 13.2 million deaths by 2030, mainly due to aging population as well as depreciation in childhood mortality and deaths from infectious disease in developing countries. In Eastern Asia number of new cancer cases ranged from 3.7 million to about 1800 in Micronesia/Polynesia. In men, the incidence of the disease is high in North America (Age-Standardized Incidence Rate (ASR), 334 per 100,000), Northern and Western Europe (ASRs 288.9 and 335.3 respectively) and Australia/New Zealand (ASR 356.8) due to high rates of Prostate Cancer in these regions (ASR > 80 per 100,000 in all). Due to high rates of breast cancer (ASRs greater than 75 per 100,000), highest incidence of cancer is found in America (ASR 274.4 per 100,000), Australia/New Zealand (ASR 276.4) and Northern and Western Europe (ASRs 257.8 and 250.5 respectively). The lowest cancer incidence rates is found in Middle and Western Africa and in South-Central Asia for men and in women it s in Middle and Northern Africa for women (ASRs less than 100 per 100,000). The ratio of ASRs in incidence for developed and developing regions are 1.8 in men and 1.6 in women, whereas ratios for mortality is much lower 1.2 and 1.0 in men and women respectively. Women in sub- Saharan Africa have same risk of dying from the disease as in women living in Central and Eastern Europe (ASRs > 90 per 100,000 in all). In developed countries a number of common cancers (prostate, breast and colorectal cancers) are associated with high survival rates, whereas in less developed regions there are several common cancers (liver, stomach and [2, 3] esophageal cancers) associated with poor prognosis. 2.1 Latin America and Caribbean In Americas cancer is second leading cause of deaths with estimated 2.5 million new cases and 1.2 million deaths annually in 2008 as per Pan American Health Organization. About half of cancer cases were observed in Latin America and the Caribbean. In Latin America, most of the countries are facing an epidemiological transition where the disease burden is drifting from infectious to chronic conditions with an increase in cáncer rates. More than 70% of cancers are actually diagnosed when it is incurable. In less developed countries cervical cancer continues to be a major threat, whereas breast and prostate cáncer rates are escalating in industrializad Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 3

countries, primarily due to dietary changes and improved standards of living. The tobacco industry flourishes across the entire region, thus anticipating that rise in smoking rates leading to lung cancer thereby emerging as a major killer in the región. In addition, weak public health programs with posible exceptions of Chile and Uruguay further hampers the cancer control across the area. As per Globocan 2008 report, the risk of getting cancer before age 75 was 18.3 % for men and 15.6 % for women. The risk of dying from cancer before age 75 was more for men (11.2%) then women (9.0%). The most common type of cancer cases and deaths are from Prostate, Lung& Bronchus and Stomach (Table 2). In Men, the age standardized incidence rate (ASR) per 100,000 was 48.4 for Prostate followed by Lung (19.0), Stomach (15.7) and then Colorectal (12.1). The mortality rate was highest for Lung cancer (17.7), followed by Prostate (16.3), Stomach (12.8), Colorectal (7.1). As in table 2, Caribbean recorded highest of newly diagnosed cancer cases for Prostate (37.3%), whereas North America showed highest for Lung & Bronchus (15.1%). In women Incidence ASR per 100,000 was highest for Breast cancer (39.7), followed by Cervix Uteri (23.5), Colorectal (7.5). The mortality ASR rate was also highest from Breast cancer (12.4), then Cervix Uteri (10.8) and Colorectal (6.1). Lowest incidence and mortality rates for men and women were from Other Pharynx and Kidney cancers respectively. Five most frequent diagnosed cancers for both sexes combined was Prostate, Breast, Lung, Cervix Uteri and Stomach. In Argentina, after cardiovascular diseases, cancer is second leading cause of death. In 2008, number of newly cancer cases diagnosed was 104,900 and age-world standardized incidence rate was 206.3/100,000 and this excluded Non-Melanoma Skin cancer. In males, mortality rate was higher for Lung, Prostate and Colorectal cancers, whereas for female s mortality rates were highest in Breast, Colorectal and Lung types of cancers. In 2008 alone, there were 18,712 Breast cancer cases diagnosed. Brazil has cancer as third leading cause of death after circulatory diseases and external causes. In 2008, number of newly cancer cases diagnosed was 321,000 and age-world standardized incidence rate was 100.4/100,000 and this excluded Non-Melanoma Skin cancer. Lung, Prostate and Stomach cancers showed higher cancer mortality rates for males, whereas for females Breast, Cervical and Lung cancer had higher mortality rates in women. In Mexico, too cancer is second leading cause of death after cardiovascular diseases. In 2008, age-world-standardized incidence rate was 128.4/100,000, excluding Non-Melanoma Skin cancer. In 2008, alone 127,600 total new cancer cases were diagnosed. Mexican men had highest mortality rates from Lung, Prostate and Stomach cancers. Breast, Cervical and Liver cancers dominated for mortality rates in Mexican [2, 4, 5, 6, 7, 8] women. Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 4

Fig. 2:- Most Common Cancer Sites Worldwide by Sex, 2008 [2] Table 1:- Estimated Number of New cancer cases and deaths Asia, America and Europe; 2008* [2] Regions Cases Deaths Male Female Overall Male Female Overall Eastern Asia 2,135,300 1,585,400 3,720,700 1,511,800 928,600 2,440,400 South Central Asia 651,100 772,000 1,423,100 496,800 483,200 979,900 South Eastern Asia 336,700 388,800 725,600 258,600 242,400 501,000 Western Asia 118,500 104,800 223,300 86,700 64,400 151,200 Caribbean 42,800 36,500 79,300 26,300 21,500 47,800 Central America 84,000 92,600 176,600 52,500 55,800 108,300 North America 831,800 772,100 1,603,900 332,500 305,900 638,300 South America 318,000 332,100 650,100 200,600 185,300 385,900 Central & Eastern Europe 494,600 490,600 985,200 351,700 283,000 634,800 Northern Europe 248,400 231,800 480,200 126,400 116,300 242,700 Southern Europe 398,800 315,000 713,900 225,000 155,500 380,500 Western Europe 569,600 464,700 1,034,300 258,900 204,900 463,800 *Excludes Non-Melanoma Skin Cancer Source: GLOBOCAN 2008 Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 5

Table2: The Two Most Common Types of New Cancer Cases and Deaths Asia, America and Europe; [2] 2008 Cancer Cases Males Females Regions First Second First Second Caribbean Prostate 37.30% Lung & Bronchus 13.00% Breast 24.60% Cervix Uteri 13.00% Central America Prostate 24.40% Stomach 9.10% Breast 18.90% Cervix Uteri 16.90% South America Prostate 26.40% Lung & Bronchus 10.60% Breast 26.60% Cervix Uteri 14.40% North America Prostate 25.70% Lung & Bronchus 15.10% Breast 26.60% Lung & Bronchus 14.30% Eastern Asia Lung & Bronchus 20.40% Stomach 19.10% Breast 15.20% Lung & Bronchus 13.20% South-Eastern Asia Lung & Bronchus 19.80% Liver 15.10% Breast 22.40% Cervix Uteri 11.40% South-Central Asia Lung & Bronchus 12.30% Oral Cavity 9.40% Cervix Uteri 22.50% Breast 22.40% Western Asia Lung & Bronchus 19.00% Colon & Rectum 8.40% Breast 27.20% Colon & Rectum 8.20% Central & Eastern Europe Lung & Bronchus 22.20% Colon & Rectum 13.00% Breast 23.40% Colon & Rectum 13.30% Northern Europe Prostate 27.30% Lung & Bronchus 14.30% Breast 30.00% Colon & Rectum 12.10% Southern Europe Prostate 20.00% Lung & Bronchus 17.00% Breast 29.00% Colon & Rectum 14.20% Western Europe Prostate 29.80% Lung & Bronchus 13.40% Breast 32.10% Colon & Rectum 13.80% Source: GLOBOCAN 2008 2.2 Central and Eastern Europe There is a significant difference in risk of different cancers and varies by geographic area. Also, there were wide variation in quality of cancer care observed especially when compared between old and new EU Members or between developed and developing countries. In Central & Eastern Europe, there is > 25% risk of dying from cancer before age 75 to that in Western Europe. This is chiefly due to access to quality and varied treatment. In Europe, people suffering from the disease are one in three and those dying from it are one in four. Each day there are more than 6,000 new cases of breast cancer (most common cancer types among women) amounting to 30.9% cases and 16.7% deaths. In men, prostate cancer is most common cancer diagnosed exhibiting 21.4% of cases and 10.4% deaths. Survival rates is considerably lower in Eastern European countries, that includes new Member states that in the 15 EU. There were 360,000 newly diagnosed cancer cases from the analysis of total population of 98 million people in all participating countries. Based on size of population, the greatest number of cases (both male and female) was found from Poland (n = 126,019) and Croatia (n=20,186) (Table 3). The highest cancer incidence was found in children (0-19 years) in Central Serbia (boys=21.7/100,000; girls=17.1/100,000); Croatia (19.1/100,000 and 16.3/100,000 respectively). The lowest incidence was seen in Hungary and Romania (11.5/100,000 and 9.1/100,000; 12.3/100,000 and Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 6

9.9/100,000) respectively. In this age group cancer was more frequently diagnosed in boys than in girls (approximately 20%) (Table3). In the age group of 20-44 years cancer incidence was much higher in women than men. In Poland incidence rates in women was 76.6/100,000 and 170.4/100,000 in Czech Republic, which is significantly higher than between rates in men in that age group. The incidence rates were highest in Central Serbia (84.3/100,000) and lowest in Poland (46.0/100,000) (Table 3) in middle aged population (45-64 years), incidence was 30% higher in men than in women. The lowest incidence was found in Poland (553.3/100,000) and Romania (544.9/100,000) and highest was in Hungary (916.1/100,000). In the age group of 45-64 years for women highest cancer incidence was found in Czech Republic, Central Serbia and Slovakia ( 627.5/100,000) whereas, lowest incidence was for Romania (397.3/100,000) (Table 3). In elderly population 65 years, the disease was diagnosed almost twice as often in men than in women. The highest incidence was seen in older men from Czech Republic (2676.7/100,000) and Slovakia (2662.5/100 000) and lowest in Romanian men (1226.1/100,000). The pattern was same in older women; highest in Slovakia (1443.1/100,000) and Czech Republic (1439.1/100,000) and lowest in Poland (923.1/100,000) and Romania (696.2/100,000) (Table 3). Sites of cancer also varied as per the countries (Table 4), Lung cancer was most common cancer in men in all selected countries, exception being Czech Republic where Prostate and Colorectal cancer were more common. The prostate cancer was third common cause of morbidity in most countries after colorectal cancer, which ranked second. The prostate cancer was recorded highest in Czech Republic and lowest in Central Serbia. The incidence of kidney cancer ranged from ~ 2% in many countries to 6.3% in Czech Republic. The kidney cancer incidence was 2-4 times higher in Czech Republic than in other countries in the region. The breast cancer incidence was highest in Romanian women with lowest in Slovakia women. The second most common tumor in women was Colorectal Cancer with exception of Romania here cervical cancer was more prevalent. The third type of cancer in women was lung cancer (Croatia, Hungary, Poland, and Central Serbia), uterine cancer (Czech Republic, Slovakia), or colorectal cancer (Romania). The kidney cancer was responsible for 2-4% of incidence of disease with highest in Czech Republic. More number cancer deaths was seen in Poland (91,632), that had highest population studied and fewest cancer deaths occurred in Slovakia (n=11,794) and Croatia (n=12,639), that had smallest of population studied. (Table 5). The proportion of deaths from cancer for men was highest for Croatia and Czech Republic (29%), while Poland and Hungary had quarter of deaths from cancer. In women, higher proportion of deaths was seen in Poland and Czech Republic (23%), whereas in other countries deaths from cancer recorded 1/5 th of all deaths except Romania, and Serbia and Montenegro (Table 5). For mortality (Table 6), in 0-19 years age bracket greatest cancer mortality were in boys from Romania (6.5/100,000) and Serbia and Montenegro (5.6/100, 000) and girls from Romania (4.8/100,000). The lowest mortality from cancer was seen in Czech Republic and Hungary (2.2-3.4/100 000). In 20-44 years age group in men highest cancer mortality was in Hungary (30.8/100,000) and Romania (28.1/100,000). In women, cancer mortality was highest in Romania (30.9/100,000), Serbia and Montenegro (29.2/100,000), and Hungary (28.9/100,000). However, in other countries cancer mortality was similar and about 50% lower. This age group showed cancer mortality rates in women that were equal to or higher than in men. Hungary showed 30-50% higher mortality rates in men and women (563.8/100,000; 275.0/100,000) in age group of 45-64 years and lowest in Romania and Croatia (210.7/100,000, 197.6/100,000) Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 7

respectively. Mortality from cancer in elderly men 65 years was same in Croatia, Czech Republic, Poland and Slovakia (1550-1675/100,000). Cancer mortality was 30-35% lower in Romania and Serbia and Montenegro, same pattern was also seen in women belonging to these countries. The highest mortality in women was found in Hungary and Czech Republic (118.1/100,000; 109.8/100,000) and lowest in Romania and Croatia (91.6/100,000; 98/100,000) (Table 6). The lung cancer has been the predominant cancer site in men in most countries then followed by colorectal cancer and prostate cancer. However, in Romania stomach cancer was in second place. Esophageal cancer was among first ten cancers in Czech Republic, Slovakia and Hungary, whereas kidney cancer was among first ten in Croatia, Czech Republic, Poland, and Slovakia. In women, breast cancer had dominated in most countries. The proportion of deaths from breast cancer was 13.1% and 17.7% in Poland and Croatia respectively. Other cancers that caused more deaths in women were lung cancer and colorectal cancer (Hungary) and colorectal cancer (Slovakia). In second place Colorectal and lung cancer caused a similar proportion in cancer mortality. In Romania Cervical cancer was third most common cause of deaths. This occurrence was not observed in other countries. In Romania, Serbia and Montenegro an increasing trend of cancer mortality was seen, but in other countries after many years of increasing mortality rates were decreasing. The most significant decrease in cancer mortality was in Czech Republic and Slovakia. In females improving trend was seen in Czech Republic, Hungary and Slovakia, with a steady reduction in mortality over many years. In other countries no change was observed in cancer mortality in women. The risk in cancer incidence is due to increase in tobacco and alcohol consumption in which Eastern Part experiences highest tobacco utilization and greatest alcohol expenditure in central part, especially Czech Republic (average [9, 10, 11] daily usage 56.9g/L in men and 14.6g/L in women). Table 3: Age Standardized incidence rates for all cancers by sex and country-croatia, Czech Republic, Hungary, Poland and Romania, Central Slovakia (last available year) [11] Male Female Country Year of data Collection n 0-19 20-44 45-64 65+ all ages n 0-19 20-44 45-64 65+ all ages Croatia 2005 11030 19.1 71.1 655.4 2255.2 314.2 9156 16.3 94.2 506.4 1078.8 210.3 Czech Republic 2005 28147 12.7 64.4 761.5 2676.7 359 26627 12 170.4 647 1439.1 286.4 Hungary 2002 26278 11.5 78.7 916.1 2504.9 386.8 22924 9.1 93.8 582.9 1381.7 250.6 Poland 2006 64092 13.8 46 553.3 1818.5 253.6 61927 12.1 76.6 506.5 923.1 191.8 Romania 2002 32244 12.3 53.9 544.9 1226.1 216.4 27655 9.9 84 397.3 696.2 163.4 Central Serbia 2004 12801 21.7 84.3 692.8 1674.7 286.2 11954 17.1 134.4 640.4 1036.5 246.7 Slovakia 2003 12159 16.9 73.2 807.4 2662.5 371.4 11841 12.5 95.9 627.5 1443.4 257.9 Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 8

Table 4: Age Standardized incidence rates for all cancers by country-croatia, Czech Republic, Hungary, Poland Romania, Serbia and Montenegro and Slovakia [11] Country Year of data Collecti on Lung Stomac h Larg e Bow el Male Prostat e Kidney Urinary Bladder Croatia 2005 64 17.7 43.5 38.7 11.1 18.4 Czech Republic 2005 58 11.2 58.7 59.5 22.6 22.3 Lung 13. 6 15. 5 Stomac h Large Bowel Breas t Female Cervix Ovary Kidne y Urinar y Bladde r 6.9 23.4 55.8 9.2 11.7 4.7 4.1 5.8 28.8 61.7 13.3 12.4 9.8 6 Hungary 2002 95 20.5 56.6 34 14.7 19.6 25 9.5 33.7 63 15.7 11.1 6.6 5.1 Poland 2006 60 12.8 29.3 27.3 9.1 15.9 15 4.9 17.2 44.5 11.5 11.1 4.7 3 Romania 2002 50 17.6 22 16.8 5.5 15.4 9 6.8 14.4 44.3 23.9 9.4 2.8 3.3 Central Serbia 2004 64 12.9 33.7 20.1 6.5 17.4 18 7.2 20.9 57.9 24.3 10.9 3.8 4.2 Slovakia 2004 56 16.1 55.5 33.9 14.9 15.9 10 7 27.7 49.7 15.2 11.5 6.6 4.1 Table 5: Cancer Mortality compared to selected mortality by country - Croatia, Czech Republic, Hungary, Poland Romania, Serbia and Montenegro and Slovakia [11] Country Year of data Collection Population (in thousands) Number of total deaths All cancer deaths Frequency of cancer deaths (%) Male Female Total Male Female Total Male Female Total Male Female Total Croatia 2005 2138.6 2303.3 4441.9 26058 25720 51778 7430 5209 12639 29 20 24 Czech Republic 2005 4991.4 5242.7 10234 54072 53866 107938 15567 12466 28033 29 23 26 Hungary 2002 4788.8 5298.2 10087 69773 65950 135723 17134 13481 30615 25 20 23 Poland 2006 18436.1 19696.2 38132 198298 171388 369686 51777 39855 91632 26 23 25 Romania 2002 10571.6 11101.7 21673 138440 120450 258890 25641 18037 43678 19 15 17 Serbia and Montenegro 2004 3947.1 4161.5 8108.7 111108 105350 216458 11216 8330 19546 10 8 9 Slovakia 2003 2615.9 2773.3 5389.2 28151 25324 53475 6906 4888 11794 25 19 22 Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 9

Table 6: Standardized Mortality rates for all cancers in selected countries - Croatia, Czech Republic, Hungary, Poland Romania, Serbia and Montenegro and Slovakia by age group and sex. [11] Male Female Country 0-19 20-44 45-64 65+ all ages 0-19 20-44 45-64 65+ all ages Croatia 3.9 22.5 410.6 1674.7 204.4 3.8 19.6 197.6 746.4 98.0 Czech Republic 2.6 17.7 375.1 1643.5 193.4 2.2 19.3 223.3 856.4 109.8 Hungary 3.4 30.8 563.8 1530.3 226.1 2.7 28.9 275.0 785.7 118.1 Poland 4.3 19.3 396.1 1602.9 195.7 3.5 20.2 243.8 725.9 105.4 Romania 6.5 28.1 404.6 1082.7 164.8 4.8 30.9 210.7 560.1 91.6 Serbia and Montenegro 5.6 25.9 388.3 1148.3 165.2 4.0 29.2 249.9 624.0 102.7 Slovakia 4.1 20.7 428.1 1594.1 201.6 4.0 18.9 218.3 707.9 99.1 2.3 Asia Demographic characteristics vary widely in different countries in Asia. Median ages in India, China and Japan are 25, 34, and 44 years respectively, yet they have exhibited inconsistent burden of cancer. About 3/4 th of new cases in Liver cancer in males and 2/3 rd in females occur in Asian countries. Furthermore, >50% of world s new Stomach cancer cases and >70% of newly diagnosed esophageal cases occurs in Asian countries. China alone contributes >1/2 of newly diagnosed liver and Esophageal cancer cases and Stomach cancer cases (42%). In 7 Asian countries, age standardized incidence rate and even mortality rate is high for lung cancer in males and breast cancer for females. In Asia population living with cancer are 3.6 million (males) and 4.0 million (females) of which China alone has 1.6 million males and 1.5 million female cancer survivors. In most of the Asian countries, Colorectal cancer for males and breast cancer for females are among most common type s survivors for cancer. As per GLOBOCAN 2008 statistics in Asia, risk of getting cancer before age 75 was 18% for males and 14.1 % for females and risk of dying from cancer before age 75 was 13.2 % for males and 8.7% for females. Five most frequent cancers for both sexes were Lung, Stomach, Liver, Breast and Colorectal in that order (ranked as per total number of cases). The cancer incidence rates in both sexes for all cancer sites tend to be highest in northeastern and lowest in southern Asian countries. Taiwan and Korea have highest of all age standardized cancer incidence rate for males in Asia (299 new cases/100,000 and 286 new cases /100,000 respectively). Total cancer incidence rate for males is 205/100,000, but due to its population size it accounts to 1.3 million estimated new male cancer cases annually, which is exceeding than that of any other Asian country. India has lowest cancer incidence rates for males in Asia (about 99/100,000males), but majors to 404,000 new male cases annually due to size of population. In US all cancer incidence rate for males is 407/100,000, which is higher than rate in any Asian country and accounts for 762,000 annual new cases. In females, all cancer incidence cases are highest in Taiwan, Singapore and Philippines, when compared to US having higher incidence than that of any Asian countries. In China, female all cancer incidence rate is 130/100,000 accounting to 867,000 annual new cancer Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 10

cases. In India, total cancer incidence rate is little higher in females (104/100,000) than in males and accounts to 448,000 new annual cases. [12] Taiwan has the highest incidence rates of Breast cancer cases (49/100,000) followed by Singapore (47/100,000) and Philippines (46/100,000). Incidence rate for breast cancer is same for China and India, 19/100,000, whereas estimated number of new cases is 126,000 (China) and 83,000 (India). Incidence rates for Breast cancer for other nations include Korea (21/100,000) and Malaysia (31/100,000). Incidence of Colorectal cancer was also highest in Taiwan and Japan; the rates were higher for males in all countries than in females. Esophageal cancer was highest in China in males (27 cases /100,000) and females (12 cases /100,000) than other Asian countries. Annually 174,000 new male cases and 80,000 new female cases on Esophageal cancer are diagnosed in China. Also, rate of Liver cancer in males was 38 per 100,000 males and females 14 per 100,000 females, thereby accounting to 251,000 and 95,000 male and female cases diagnosed annually. In males, incidence rate for Lung cancer is highest for Korea, Philippines, Singapore, and China and lowest for India and Sri Lanka; however in females its highest for China, Singapore and Taiwan and lowest again for India and Sri Lanka. Adequate screening measures have led to higher incidence rates in cancer types, which can be seen for Prostate cancer in US than any of the Asian countries. In Asia, however Taiwan shows higher incidence of prostate cancer incidence followed by Philippines as compared to other Asian nations. Stomach cancer predominates other types of cancers in Korea in both sexes (70 and 27 per 100,000 males and females, respectively), followed by Japan, Mongolia and China. India and Cambodia have highest incidence rates of uterine cervix cancer, whereas China and Japan have lowest rates. In males for all new cancer cases diagnosed China occupies 23% and India 7%. China alone provides 57% of new male liver cases, esophageal (55% of new male cases) and Stomach (44% new male cases). About 1/3 rd (28%) of world s new male lung cancer cases is in China and Japan (5%), together contributing also more than a quarter of new male Colorectal cancers worldwide. Also, 17% (1 in 6) of world s new female cancer cases occurs in China. Similar to male cases, China also gives 52% of new female Liver cases, esophageal (55%), Stomach (39%of new cases). Japan (11% for new female Stomach cancer cases). The Asian countries accounts for almost half of all new Uterine Cervix cases with India alone diagnosing 27% of the cases. [12] 4BFemales in Asian countries are more likely than men to survive from cancer. Korea, Taiwan, Singapore, China and Japan have rates ranging from 180-154 deaths/100,000 in males. Thailand and Vietnam males have mortality to incidence ratio of 0.81 and are least likely to survive from cancer. Highest rates of survival in males are seen in Japan (0.59), Taiwan (0.60) and Korea (0.63). But, when compared to US (0.38), these Asian nations males have a very low survival rate. In females, all cancer mortality rate is highest in Mongolia (136 per 100,000 population), followed by Philippines and Singapore (124 and 109 per 100,000 population, respectively). Survival is highest in Taiwan with mortality to incidence ratio 0.44 but less when compared to US females where ratio is 0.36. Mortality rate from breast cancer is highest in Philippines (27/100,000) and lowest survival rate (mortality to incidence ratio: 0.58) among other Asian countries. Survival rates are highest in Korea (0.22), Taiwan (0.22) and Japan (0.25), but Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 11

less likely than US (mortality to incidence ratio: 0.19). Singapore (20 deaths /100,000), Taiwan (18 deaths /100,000), and Japan (17 deaths /100,000), have higher mortality rates for colorectal cancer for males and also for females in same type of cancer. Survival rates for this type of cancer are highest for Taiwan (0.40), Japan (0.42) and Korea (0.42). Having mortality to incidence ratio of 0.35 males in Japan are more likely to survive from colorectal cancer than females. Esophageal cancer is highest in males in China (22/100,000). China is the third highest in mortality rate among females for Esophageal cancer (10/100,000). Survival is lower across all other countries for cancer of Esophagus. Mongolia has highest liver cancer mortality rates in males (93/100,000) and females (47/100,000). Other countries with high mortality rates in males are Taiwan (40/100,000), Thailand, Korea and China (35/100,000) and for females it s in Thailand (17/100,000), Taiwan (14/100,000) and China (13/100,000). Survival from Liver cancer is however generally poor in these countries. Lung cancer mortality rates are higher for males than females in all countries. Philippines, Singapore and Korea surpass 40/100,000 and nearing to US (49/100,000). China and Taiwan have same mortality rate from Lung cancer (37/100,000). In females, Lung cancer mortality rate is highest in Singapore (18/100,000), and then followed by Taiwan (16/100,000) and China (16/100,000). Philippines shows highest mortality rate for Prostate cancer (13/100,000) than any other Asian countries. Survival from Prostate cancer is greatest in Taiwan and Korea with mortality to incidence ratios 0.33 & 0.37 respectively. Stomach cancer deaths in men are more in Korea (37/100,000), and then followed by China & Mongolia (33/100,000). In females, stomach cancer mortality rates are higher for Mongolia (19/100,000), followed by China (15/100,000) and Korea (15/100,000). In Japan, mortality rates are (29 males/100,000 and 13 females/100,000). Japan has highest survival rates for cancer of stomach. Uterine Cervix mortality in India is 18/100,000. Whereas, Korea has highest survival rate bearing a mortality to incidence ratio of 0.26. [12] 3.0 Prevalence In Latin America and Caribbean, as in 2008 in Men, five year prevalence rate was 37.1% for Prostate cancer, then Colorectal (8%) and Stomach (7.0%). In women, 5 year prevalence recorded for Breast Cancer was 34.7%, which was then followed by Cervix Uteri (18.8%) and Colorectal (6.9%). The 5 year prevalent cases were 950/100,000 for men and 1196/100,000 for women. Males had higher risk of getting cancer before 75 years of age than women (18.3% vs. 15.6%). Also, mortality from disease before 75 years was higher for men (11.2%) than women (9%). Based on number of cases received, top five cancers for both sexes combined in the region were Prostate, Breast, Lung, Cervix Uteri, Stomach. [8] In Europe, incidence of cancer in men is greater in North-Western Europe, but death rate is higher in Central and Eastern Europe. In females, incidence of having a cancer is also higher in North Western Europe, however mortality is similar in both (North Western and Central Eastern) regions. A decline in mortality has been seen since mid 1980 s, but started to decline in Central & Eastern Europe recently. In Central & Eastern Europe, in 2008, top five most frequent cancers (ranked defined by total number of cases were Lung, Colorectal, Breast, Stomach and Prostate for both sexes combined. The risk of getting cancer before age was 75 was 27% for men, 18.9% Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 12

for women and 22.1 % for both sexes. Mortality before age 75 was also higher for men (19.4%) than in women (10.1%) and 13.9% for both sexes. 5 year prevalence rate was higher for women than in men. In men, in Central and Eastern European region, 5 year prevalent cases were higher for Prostate (18.5%) followed by Colorectal (15.5%) and Lung Cancers (11.4%). In women, breast cancer showed higher prevalent cases (33.1%) than any other types of cancer, which was then subsequently seen for Colorectal (11.8%), Corpus uteri (11.1%), Cervix uteri(8.1%) and Ovarian cancer (5%). [13] In Asia, in 2008, top 5 cancers combined in both sexes based on total number of cases got were Lung, stomach, Liver, Breast and Colorectal, in that order. China alone had 1.6 million males and 1.5 million female cancer survivors. Colorectal cancer was found to be most common cancer in male cancer survivors and also ranked among top 5 cancers in the region. Stomach cancer was found to be more prevalent in male cancer patients in China (365,000 survivors). In India, Oral cancer was seen to be more prevalent. Except Mongolia, Breast cancer ranked first or second most prevalent form of female cancer survivors. In India, in females Uterine Cervix (370,000 survivors) were noticed. Also, in female s Uterine Cervix cancer ranked among top 5 prevalent forms of cancer in the region. Before age 75, risk of getting cancer and dying from it was higher in males (18% & 13.2 %) than in females (14.1% & 8.7%). In India, Oral cavity (23.8/100,000) in males and Uterine Cervix cancer (73.6/100, 000) in females was seen to be more prevalent, whereas Breast cancer (53.5/100,000) ranked behind. In Korea Stomach (82.8/100,000) cancer in males and Breast cancer in females (75.9/100,000) were seen more prevalent. In Korea and Malaysia both sexes had Lung and Bronchus and Colorectal cancer as common type; however their prevalent rates varied differently. In Malaysia, Colorectal cancer (31.5/100,000) and Breast cancer (94.9/100,000) in females were at top in prevalent forms of cancer. In Philippines and Singaporean males Colon and rectum cancer had higher prevalent rates 23.5/100,000 and 84.8/100,000 respectively, whereas in females of these countries Breast cancer had more survivors with 10.35/100,000 for Philippines and 202.5/100,000 for Singapore. Thailand had higher 5 year prevalent rate for Colon and Rectum cancer (20.9/100,000) than any other form of cancer for males and females had Uterine Cervix (62.6/100,000) to be prevalent. Tables 7 (a & b), shows number of males and females living with cancer and diagnosed from it in past 5 years, [12, 14] by country. Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 13

Table 7a: Number of males living with cancer and diagnosed within past 5 years, by country [12] Table 7b: Number of females living with cancer and diagnosed within past 5 years, by country [12] Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 14

4.0 Oncology Clinical Trials in Emerging Markets Fig. 3: Phase wise distribution of oncology clinical trials in emerging markets (n=6380). [15] Fig. 4: Percentage Contributions by emerging markets on oncology clinical trials (n=6380). [15] Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 15

References: 1. Ahmedin, J, et al.; Global Cancer Statistics; Volume 61, Issue 2, pages 69 90, March/April 2011. 2. Global Cancer Facts & Figures - 2nd Edition; www.cancer.org/acs/groups/content/.../document/acspc-027766.pdf 3. All Cancers (excluding non-melanoma skin cancer) Incidence and Mortality Worldwide in 2008; Globocan 2008; http://globocan.iarc.fr/factsheets/cancers/all.asp 4. 5. 6. 7. 8. TheCancerBurdeninLatinAmerica;AmericanCancerSociety; http://www.cancer.org/aboutus/globalhealth/globalinitiativesbyregion/latin-america CancerBurdeninArgentina,NationalCancerInstitute; http://www.cancer.gov/aboutnci/organization/olacpd/crn/argentina CancerBurdeninBrazil,NationalCancerInstitute; http://www.cancer.gov/aboutnci/organization/olacpd/crn/brazil CancerBurdeninMexico,NationalCancerInstitute; http://www.cancer.gov/aboutnci/organization/olacpd/crn/mexico Latin America And Caribbean; Globocan 2008; http://globocan.iarc.fr/factsheet.asp 9. Compared to Western Europe, Central and Eastern Europeans are 25% more likely to die of cancer before the age of 75 ; European Cancer Patient Coalition; Press Release dated 27 November 2010; http://www.ecpc-online.org/press-room/376-central-eastern-europeans-more-likely-to-die-ofcancer.html 10. Zatoński, W, Didkowska, J, Closing the gap: Cancer in Central and Eastern Europe (CEE); Eur J Cancer; July 2008; 44 (10); 1425-1437 11. Vrdoljak, E, et.al; Cancer Epidemiology in Central and South Eastern European Countries; Croat Med J. 2011; 52:478-87 12. Burden of Cancer in Asia, Pfizer, 2008 13. Central and Eastern Europe; Globocan 2008; http://globocan.iarc.fr/factsheet.asp 14. Asia; Globocan 2008; http://globocan.iarc.fr/factsheet.asp 15. Clinical Trials.gov. Accessed, 1/30/2012. This information does not constitute a written advisory opinion of the Author, but rather is official information available through up to date literature survey. This information does not necessarily represent the formal position of MC SMO, and does not bind or otherwise obligate or commit the MC SMO to the information presented. Toll Free : (888) 987-2691 www.makrocare.com/mcsmo 16