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101
MALAYSIAN STATISTICS ON MEDICINES 2008
Chapter 16 | USE OF ANTINEOPLASTIC AGENTS, INCLUDING ENDOCRINE THERAPY AND IMMUNOSTIMULANTS
Azura D.1, Ibtisam M.N.1, Voon F.K.2, Nor Saleha I.T.3, Tajunisah M.E.4, Wan Nazuha W.R1
1. Kuala Lumpur Hospital, Kuala Lumpur, 2. UKM Medical Centre, Selangor, 3. Disease Control Division, Ministry of Health, 4. Pulau Pinang Hospital, Pulau Pinang.
Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths (around 13% of all deaths) in 2008. Deaths from cancer worldwide are projected to continue to rise, with an estimated 13.1 million deaths in 2030.1 Malignant neoplasm was among the top five principle cause of death in the Ministry of Health (MOH) hospitals in 2011.2 According to the National Cancer Registry 2007, 18,219 new cancer cases were reported in Malaysia. The estimated Age- Standardised Incidence Rate (ASR) was 85.1 per 100,000 in males and 94.4 per 100,000 in females.3
The Defined Daily Dose (DDD) is the measurement unit adopted primarily in other chapters in this Malaysian Statistics on Medicines report to reflect the average maintenance dose per day for a drug used in its main indication in adults.4 However, there is no assigned DDD for antineoplastics because of its highly individualised use and wide dosage ranges. Antineoplastics are also usually given as combination therapy for specific number of cycles per patient and not continuously.
In this report, the total utilisation of antineoplastics is described similarly to the previous report in 2007. For the purpose of comparing usage between the agents, an estimation of the number of cycles used were done using the standard dose for the main indication in adults,5,6 standardised Body Surface Area (BSA) of 1.72m2 and standardised weight of 60 kg.7 Agents that are prescribed daily were calculated as a monthly cycle comprising of 28 days.
Total Number of Treatment Cycles = T / Proposed DDD
where
The 10 antineoplastic agents with the highest overall usage were carboplatin, cyclophosphamide, 5-flurouracil, methotrexate, doxorubicin, cisplatin, hydroxycarbamide, mercaptopurine, epirubicin and dactinomycin.
Comparing the public and private, the top 10 antineoplastics used in the public sector were carboplatin, cyclophosphamide, fluorouracil, methotrexate, doxorubicin, cisplatin, hydroxycarbamide, mercaptopurine, epirubicin and dactinomycin. In the private sector, cyclophosphamide, fluorouracil, gemcitabine, carboplatin, doxorubicin, hydroxycarbamide, oxaliplatin, capecitabine, cisplatin and paclitaxel were the 10 most used agents.
According to the different drug classes, the most used alkylating agent was cyclophosphamide followed by ifosfamide and mephalan. Carmustine, melphalan and busulphan are part of conditioning regimens for transplant and the usage has increased due to increase in number of transplants.
For antimetabolites, fluorouracil was the most used agent followed by methotrexate and mercaptopurine. There was a marked increment of methotrexate due to an increase in incidence of CNS lymphoma and acute lymphoblastic leukemia (ALL). It is also used in salvage therapies for lymphoma, paediatric malignancies and ALL.
There was a decrease in usage of pemetrexed likely due to availability of targeted therapy for EGFR mutated lung cancer.
For vinca alkaloids, vincristine was most frequently used. Etoposide was the most common agent in the podophyllotoxin class but the usage has reduced. Paclitaxel was the most common agent in the taxane group but the usage has also reduced. In the anthracycline group, doxorubicin is the most used followed by epirubicin and dactinomycin.
In the platinum group, there is a drastic increase in usage for carboplatin surpassing cisplatin. This is surprising and may indicate a changing trend from cisplatin usage to carboplatin in the future. It will be compared with the future report.
The usage of tretinoin has increased due to the increase in incidence of acute promyelocytic leukemia (APML). However, the usage of arsenic trioxide which is the second line for relapse APML remained the same for both years.
T
T
D/1000pop
P
= (D/1000pop
*P*365)/1000
= an estimate of the total quantity of the drug utilised in the year (mg/mcg/iu)
= Dosage per 1000 population (mg/mcg/iu)
= mid-year population of Malaysia
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MALAYSIAN STATISTICS ON MEDICINES 2008
For targeted therapy, rituximab is still the most commonly prescribed monoclonal antibody followed by bevacizumab and trastuzumab. It was noted that the use of trastuzumab has increased in the public sector as it was made available in the MOH formulary in 2008. In terms of small molecules, gefitinib is ranked highest in usage, followed by imatinib and lapatinib. The increase in imatinib reflects its availablity through patient assistance program for chronic myeloid leukaemia and gastrointestinal stromal tumor. Dasatinib and nilotinib were introduced in 2008 as 2nd generation tyrosine kinase inhibitors. The use of Erlotinib has decreased significantly.
By using the above formula proposed in the 2007 report, we are able to compare and conclude these data and observe the changes in the trends of prescribing antineoplastic drugs. However, we propose to incorporate the cost and number of patients in future reports for international comparisons.
ENDOCRINE THERAPY
Hormonal therapy is commonly used for breast and prostate cancer. The use in prostate cancer is discussed in the urology section (Chapter 13).
In terms of the different agents, tamoxifen remains the most used antioestrogens in 2008. This was followed by letrozole and anastrazole. Letrozole is the most used aromatase inhibitor for year 2008. The total usage of tamoxifen had reduced in 2008 compared to 2007. We also noted that the use of anastrazole has reduced by half.
IMMUNOSTIMULANTS
Colony stimulating factors are used as prophylaxis or treatment of neutropenia. Filgrastim was the most used colony stimulating factor. Pegfilgrastim is still mainly used in the private sector.
Interferons may be used in the treatment of renal cancer, Kaposi’s sarcoma, haematological malignancies and non-malignant conditions. The most frequently used interferon is interferon alfa 2b followed by interferon alfa 2a. The use of interferon alfa 2a had reduced drastically possibly due to the availability of newer agents.
ATC Drug Class & Agents
Dose &Duration
AverageDose per treatment
cycle
Unit Sector
2007 2008
TotalDosage /1000
population
Total no. of
treatment cycle
TotalDosage /1000
population
Total no. of
treatment cycle
L01A A Nitrogen mustard analogues
L01A A01 Cyclophosphamide 750mg/m2 1300 mg
Public 2.1746 16591 2.4588 16976
Private 0.6602 5037 0.5840 5154
Total 2.8348 21628 3.0428 22130
L01A A02 Chlorambucil 10mg d1-14 140 mg
Public 0.0040 283 0.0040 289
Private 0.0009 61 0.0002 62
Total 0.0048 344 0.0043 352
L01A A03 Melphalan 30mg/m2 50 mg
Public 0.0012 234 0.0039 239
Private 0.0010 192 0.0005 196
Total 0.0021 426 0.0044 436
L01A A06 Ifosfamide1500mg/m2
x 5/712900 mg
Public 0.0016 1 0.0011 1
Private 0.0002 <1 0.0001 <1
Total 0.0018 1 0.0012 1
L01A B Alkyl sulfonates
L01A B01 Busulfan0.8mg/kg QID
x 4/7800 mg
Public 0.0051 64 0.0157 65
Private 0.0020 24 0.0001 25
Total 0.0071 88 0.0158 90
Table 16.1: Use of Anti-Neoplastic Agents by Drug Class and Agents, in DDD/1000 population/day 2007-2008
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MALAYSIAN STATISTICS ON MEDICINES 2008
ATC Drug Class & Agents
Dose &Duration
AverageDose per treatment
cycle
Unit Sector
2007 2008
TotalDosage /1000
population
Total no. of
treatment cycle
TotalDosage /1000
population
Total no. of
treatment cycle
L01A C Ethylene imines
L01A C01 Thiotepa45mg/m2
weekly80 mg
Public 0.0001 8 <0.0001 8
Private - - - -
Total 0.0001 8 <0.0001 8
L01A D Nitrosoureas
L01A D01 Carmustine300mg/m2
x1/7500 mg
Public 0.0006 11 0.0022 11
Private 0.0013 25 0.0015 26
Total 0.0018 36 0.0036 37
L01A D02 Lomustine 110mg/m2 d1 190 mg
Public 0.0006 31 0.0007 32
Private 0.0002 12 0.0001 13
Total 0.0008 43 0.0008 44
L01A X Other alkylating agents
L01A X03 Temozolomide75mg/m2
d1-5 x 6 weeks
3900 mg
Public 0.0046 12 0.0125 12
Private 0.0096 24 0.0103 25
Total 0.0142 36 0.0228 37
L01A X04 Dacarbazine375mg/m2
D1+151300 mg
Public 0.1002 765 0.0895 782
Private 0.0330 251 0.0131 257
Total 0.1332 1016 0.1026 1040
L01B A Folic acid analogues
L01B A01 Methotrexate 2000mg/m2 3500 mg
Public 0.7348 2082 4.0560 2131
Private 0.1913 542 0.1738 555
Total 0.9261 2624 4.2298 2685
L01B A04 Pemetrexed 500mg/m2 860 mg
Public 0 0 0.0004 0
Private 0.0092 106 0.0066 108
Total 0.0092 106 0.0070 108
L01B B Purine analogues
L01B B02 Mercaptopurine100mg/m2
d1-5860 mg
Public 0.8572 9886 0.6260 10115
Private 0.1464 1688 0.0181 1728
Total 1.0036 11574 0.644 11843
L01B B03 Tioguanine100mg/m2
d1-5860 mg
Public 0.0822 948 0.0695 970
Private 0.0048 55 0.0002 56
Total 0.0870 1003 0.0697 1026
L01B B04 Cladribine0.2mg/kg
d1-560 mg
Public <0.0001 3 <0.0001 3
Private <0.0001 3 <0.0001 3
Total <0.0001 5 <0.0001 5
L01B B05 Fludarabine25mg/m2
d1-5215 mg
Public 0.0073 337 0.0032 345
Private 0.0013 61 0.0002 62
Total 0.0086 397 0.0034 407
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ATC Drug Class & Agents
Dose &Duration
AverageDose per treatment
cycle
Unit Sector
2007 2008
TotalDosage /1000
population
Total no. of
treatment cycle
TotalDosage /1000
population
Total no. of
treatment cycle
L01B C Pyrimidine analogues
L01B C01 Cytarabine1500mg/m2 b
BD x 4/720640 mg
Public 1.4036 674 1.8288 690
Private 0.2533 122 0.8669 125
Total 1.6569 796 2.6957 815
L01B C02 Fluorouracil 1000mg/m2 2000 mg
Public 4.1618 20639 4.1341 21118
Private 1.3773 6830 0.8548 6989
Total 5.5391 27469 4.9889 28107
L01B C03 Tegafur300mg/m2
x 21days rest 7days
10836 mg
Public 0 0 0 0
Private 0 0 0.0116 0
Total 0 0 0.0116 0
L01B C05 Gemcitabine1000mg/m2
d1+ 83440 mg
Public 0.9037 2606 0.5806 2666
Private 0.4505 1299 1.0374 1329
Total 1.3542 3904 1.6179 3995
L01B C06 Capecitabine2500mg/d
d1- 1435000 mg
Public 11.2026 3175 7.1037 3248
Private 10.8932 3087 7.3898 3159
Total 22.0958 6262 14.4935 6407
L01B C08 Decitabine20mg/m2/d
x 5days172 mg
Public 0 0 0 0
Private 0 0 0.0001 0
Total 0 0 0.0001 0
L01B C53 Tegafur, combinations100mg tds x
28 days8400 mg
Public 0.0121 14 0.0002 15
Private 0.1773 209 0.1490 214
Total 0.1894 224 0.1492 229
L01C A Vinca alkaloids and analogues
L01C A01 Vinblastine 10mg d1+15 20 mg
Public 0.0014 671 0.0031 686
Private 0.0018 870 0.0004 891
Total 0.0031 1541 0.0035 1577
L01C A02 Vincristine 2mg d1+8 4 mg
Public 0.0019 4706 0.0018 4816
Private 0.0004 1007 0.0002 1030
Total 0.0023 5714 0.0019 5846
L01C A04 Vinorelbine30mg/m2
d1+8100 mg
Public 0.0027 264 0.0064 270
Private 0.0057 561 0.0070 574
Total 0.0083 825 0.0134 844
L01C B Podophyllotoxin derivatives
L01C B01 Etoposide100mg/m2
d1-5860 mg
Public 0.1796 2072 0.1175 2120
Private 0.0425 490 0.0318 502
Total 0.2221 2562 0.1493 2621
L01C B02 Teniposide 100mg/m2 860 mg
Public 0.0006 7 0.0011 7
Private 0.0014 17 0.0002 17
Total 0.0020 23 0.0014 24
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MALAYSIAN STATISTICS ON MEDICINES 2008
ATC Drug Class & Agents
Dose &Duration
AverageDose per treatment
cycle
Unit Sector
2007 2008
TotalDosage /1000
population
Total no. of
treatment cycle
TotalDosage /1000
population
Total no. of
treatment cycle
L01C D Taxanes
L01C D01 Paclitaxel 175mg/m2 300 mg
Public 0.1014 3351 0.0613 3429
Private 0.0464 1534 0.0462 1570
Total 0.1478 4885 0.1075 4998
L01C D02 Docetaxel 75mg/m2 130 mg
Public 0.0279 2126 0.0254 2175
Private 0.0212 1621 0.0185 1658
Total 0.0491 3746 0.0439 3833
L01D A Actinomycines
L01D A01 Dactinomycin 15mcg/kg 1 mcg
Public 0.0003 2661 0.0006 2722
Private <0.0001 70 <0.0001 71
Total 0.0003 2730 0.0006 2794
L01D B Anthracyclines and related substances
L01D B01 Doxorubicin 50mg/m2 90 mg
Public 0.0775 8536 0.0827 8734
Private 0.0253 2786 0.0202 2851
Total 0.1027 11322 0.1029 11585
L01D B02 Daunorubicin45mg/m2
d1-3230 mg
Public 0.0134 578 0.0076 592
Private 0.0016 70 0.0010 71
Total 0.0150 648 0.0086 663
L01D B03 Epirubicin 75mg/m2 130 mg
Public 0.0857 6539 0.0811 6691
Private 0.0165 1256 0.0142 1286
Total 0.1022 7796 0.0953 7977
L01D B06 Idarubicin12mg/m2
d1-3105 mg
Public 0.0009 81 0.0013 83
Private 0.0003 27 0.0003 28
Total 0.0011 108 0.0017 111
L01D B07 Mitoxantrone12mg/m2
d1-360 mg
Public 0.0009 146 0.0025 150
Private 0.0004 67 0.0014 69
Total 0.0013 213 0.0039 218
L01D C Other cytotoxic antibiotics
L01D C01 Bleomycin30mg/m2 d1, 8, 15
90 mg
Public 0.0062 685 0.0062 701
Private 0.0020 218 0.0016 223
Total 0.0082 903 0.0078 924
L01D C03 Mitomycin 12 mg
Public 0.0021 1754 0.0023 1795
Private 0.0011 875 0.0012 896
Total 0.0032 2629 0.0036 2690
L01X A Platinum compounds
L01X A01 Cisplatin 75mg/m2 130 mg
Public 0.0969 7396 0.1042 7567
Private 0.0397 3029 0.0240 3100
Total 0.1366 10425 0.1283 10667
L01X A02 Carboplatin 500 mg
Public 0.2276 4515 0.2457 4620
Private 0.1277 2534 0.1277 2593
Total 0.3554 7049 0.3734 7213
L01X A03 Oxaliplatin 85mg/m2 150 mg
Public 0.0370 2447 0.0257 2504
Private 0.0394 2603 0.0293 2663
Total 0.0764 5050 0.0551 5167
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MALAYSIAN STATISTICS ON MEDICINES 2008
ATC Drug Class & Agents
Dose &Duration
AverageDose per treatment
cycle
Unit Sector
2007 2008
TotalDosage /1000
population
Total no. of
treatment cycle
TotalDosage /1000
population
Total no. of
treatment cycle
L01X B Methylhydrazines
L01X B01 Procarbazine100mg/m2
d1-14 [max 150mg]
2100 mg
Public 0.0071 33 0.0253 34
Private 0.0185 87 0.0009 89
Total 0.0256 121 0.0263 123
L01X C Monoclonal antibodies
L01X C02 Rituximab 375mg/m2 500 mg
Public 0.0697 1383 0.0831 1415
Private 0.0512 1015 0.0466 1039
Total 0.1209 2399 0.1297 2454
L01X C03 Trastuzumab 6mg/kg 400 mg
Public 0.0004 11 0.0083 11
Private 0.0139 345 0.0361 353
Total 0.0143 356 0.0443 364
L01X C04 Alemtuzumab30mg
[3x/week]90 mg
Public - - 0.0004 -
Private 0.0004 45 <0.0001 46
Total 0.0004 45 0.0004 46
L01X C05 Gemtuzumab - 5 mg
Public <0.0001 20 <0.0001 21
Private <0.0001 40 <0.0001 41
Total <0.0001 60 <0.0001 62
L01X C06 Cetuximab250mg/m2
d1+15800 mg
Public - - 0.0035 0
Private 0.0229 284 0.0279 291
Total 0.0229 284 0.0314 291
L01X C07 Bevacizumab 5mg/kg 300 mg
Public - - <0.0001 -
Private 0.0281 928 0.0328 950
Total 0.0281 928 0.0329 950
L01X E Protein kinase inhibitors
L01X E01 Imatinib400mg od x 28 days
11200 mg
Public 0.1757 156 0.5571 159
Private 0.1389 123 0.1898 126
Total 0.3145 279 0.7469 285
L01X E02 Gefitinib250mg od x 28 days
7000 mg
Public - - 0.0450 -
Private 0.1896 269 0.4131 275
Total 0.1896 269 0.4581 275
L01X E03 Erlotinib100mg od x 28 days
2800 mg
Public 0.0046 16 0.0063 17
Private 0.0892 316 0.0165 323
Total 0.0938 332 0.0228 340
L01X E04 Sunitinib37.5mg x 4/52
rest 2/521050 mg
Public 0.0003 3 0.0036 3
Private 0.0048 45 0.0004 46
Total 0.0051 48 0.0040 49
L01X E05 Sorafenib400mg bd x 28 days
22400 mg
Public 0.0054 2 0.0001 2
Private 0.0859 38 0.0365 39
Total 0.0913 40 0.0366 41
L01X E06 Dasatinib70mg bd x 28 days
3920 mg
Public - - 0.0083 -
Private 0.0007 2 0.0035 2
Total 0.0007 2 0.0118 2
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ATC Drug Class & Agents
Dose &Duration
AverageDose per treatment
cycle
Unit Sector
2007 2008
TotalDosage /1000
population
Total no. of
treatment cycle
TotalDosage /1000
population
Total no. of
treatment cycle
L01X E Protein kinase inhibitors
L01X E07 Lapatinib1250mg od x 28 days
35000 mg
Public - - - -
Private 0.0418 12 0.2374 12
Total 0.0418 12 0.2374 12
L01X E08 Nilotinib400mg bd x 28 days
38528 mg
Public - - 0.0192 -
Private - - 0 -
Total - - 0.0192 -
L01X E09 Temsirolimus25 mg per week x 4
100 mg
Public - - - -
Private - - 0.0002 -
Total - - 0.0002 -
L01X X Other antineoplastic agents
L01X X02 Asparaginase 10000iu/m2 20000 iu
Public 4.7908 2376 4.0042 2431
Private 0.8304 412 0.4671 421
Total 5.6212 2788 4.4713 2852
L01X X05 Hydroxycarbamide500mg tds x 28 days
42000 mg
Public 28.3178 6687 32.2063 6843
Private 8.3229 1965 9.0130 2011
Total 36.6407 8653 41.2193 8854
L01X X11 Estramustine280mg tds
d1-54200 mg
Public - - - -
Private 0.1211 286 0.0106 293
Total 0.1211 286 0.0106 293
L01X X14 Tretinoin45mg/m2
d1- 15 q12 weeks
1160 mg
Public 0.0181 155 0.0262 159
Private 0.0122 104 0.0003 106
Total 0.0303 259 0.0265 265
L01X X17 Topotecan1.25mg/m2
d2-610 mg
Public - - <0.0001 -
Private <0.0001 5 <0.0001 5
Total <0.0001 5 <0.0001 5
L01X X19 Irinotecan 180mg/m2 310 mg
Public 0.0354 1133 0.0227 1159
Private 0.0118 376 0.0115 385
Total 0.0472 1509 0.0342 1544
L01X X23 Mitotane10 g per day
x 28280000 mg
Public - - 0.0029 -
Private - - - -
Total - - 0.0029 -
L01X X27 Arsenic trioxide10mg od x 42 days
420 mg
Public 0.0003 7 0.0004 7
Private - - 0.0001 -
Total 0.0003 7 0.0005 7
L01X X32 Bortezomib1.3mg/m2 d1, 4, 8, 11 q21 days
9 mg
Public <0.0001 33 0.0001 34
Private 0.0001 73 <0.0001 74
Total 0.0001 106 0.0001 109
L01X X35 Anagrelide0.5mg bd x 28 days
28 mg
Public 0.0042 1490 0.0045 1525
Private 0.0026 930 0.0002 951
Total 0.0068 2420 0.0047 2476
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MALAYSIAN STATISTICS ON MEDICINES 2008
ATC DRUG CLASS AND AGENTS UNIT SECTOR 2007 2008
L02A B Progestogens
L02A B01 Megestrol g
Public - <0.0001
Private 0.0057 0.0032
Total 0.0057 0.0032
L02A B02 Medroxyprogesterone g
Public 0.0001 0.0004
Private <0.0001 <0.0001
Total 0.0002 0.0004
L02A E Gonadotropin releasing hormone analogues
L02A E01 Buserelin mg
Public - -
Private 0.0002 0.0004
Total 0.0002 0.0004
L02A E02 Leuprorelin mg
Public 0.0114 0.0111
Private 0.0076 0.0122
Total 0.0190 0.0232
L02A E03 Goserelin mg
Public 0.0174 0.0179
Private 0.0129 0.0101
Total 0.0303 0.0279
L02A E04 Triptorelin mg
Public 0.0010 0.0016
Private 0.0003 0.0002
Total 0.0014 0.0017
L02B A Anti-estrogens
L02B A01 Tamoxifen mg
Public 0.1483 0.1444
Private 0.0565 0.0360
Total 0.2048 0.1804
L02B A03 Fulvestrant mg
Public - -
Private <0.0001 <0.0001
Total <0.0001 <0.0001
L02B B Anti-androgens
L02B B01 Flutamide g
Public 0.0023 0.0015
Private 0.0008 0.0004
Total 0.0031 0.0019
L02B B03 Bicalutamide mg
Public 0.0094 0.0093
Private 0.0037 0.0024
Total 0.013 0.0117
L02B G Enzyme inhibitors
L02B G03 Anastrozole mg
Public 0.0092 0.0043
Private 0.0044 0.0028
Total 0.0136 0.0071
L02B G04 Letrozole mg
Public 0.0112 0.0103
Private 0.0054 0.0041
Total 0.0167 0.0144
L02B G06 Exemestane mg
Public <0.0001 0.0001
Private 0.0005 0.0005
Total 0.0006 0.0006
Table 16.2: Use of Anti-Neoplastic Agents by Drug Class, in DDD/1000 population/day 2007-2008
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MALAYSIAN STATISTICS ON MEDICINES 2008
ATC DRUG CLASS AND AGENTS UNIT SECTOR 2007 2008
L03A A Colony stimulating factors
L03A A02 Filgrastim mg
Public 0.0028 0.0031
Private 0.0012 0.0010
Total 0.0040 0.0041
L03A A10 Lenograstim mg
Public 0.0001 0.0002
Private <0.0001 0.0002
Total 0.0002 0.0003
L03A A13 Pegfilgrastim mg
Public - <0.0001
Private 0.0001 0.0005
Total 0.0001 0.0005
L03A B Interferons
L03A B04 Interferon alfa-2a MU
Public 0.0004 0.0001
Private 0.0001 -
Total 0.0005 0.0001
L03A B05 Interferon alfa-2b MU
Public 0.0018 0.0015
Private 0.0002 0.0001
Total 0.0020 0.0016
L03A C Interleukins
L03A C01 Aldesleukin mg
Public - -
Private - <0.0001
Total - <0.0001
Table 16.3: Use of Anti-Neoplastic Agents by Drug Class, in DDD/1000 population/day 2007-2008
References:
1. World Health Organization (WHO), Fact Sheet – Cancer. Available at http://www.who.int/mediacentre/factsheets/fs297/en/index.html [viewed 30 August 2012.
2. Health Facts 2011. Health Informatics Centre Planning and Development Division, Ministry of Health Malaysia
3. National cancer Registry Malaysia Cancer Statistics Data and Figure 2007, Ministry of Health Malaysia
4. Australian Government Department of Health and Ageing. Australian Statistics on Medicines. 2007 13th Edition. Commonwealth of Australia 2009
5. Systemic Therapy of Cancer Protocol. Ministry of Health and Ministry of Higher Education Malaysia, 2nd Edition, 2011
6. Ampang Protocol of Haematology Department. Ampang Hospital 2010
7. Mosteller RD, Simplified Calculation of BSA, New England Journal Medicine 1987; 317:1098
8. WHO Collaborating Centre for Drug Statistics Methodology, Guidelines for ATC Classification and DDD Assignment 2011, Oslo 2010
