Lesson I

Pubmed
Topic

Total abstracts

Relevant abstracts

Full texts available

Landmark papers

Bosutinib and
pharmacodynamics

158

64

20

Bosutinib and
pharmacokinetics

28

11

Bosutinib and (meta

analysis or meta
network or systemic
review)

Bosutinib
randomized
controlled trial

14

Bosutinib and
adverse effect

Bosutinib and
quality of life

Bosutinib and (cost

utility or cost
effective)

Bosutinib and
health technology
assessment

1. What are the indications approved of your study drug based on the US or EU FDA?
ANS Bosutinib is a kinase inhibitor indicated for treatment of adult patients with chronic, accelerated, or
blast phase Ph+ chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy.
Reference: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203341lbl.pdf
2. What are the drugs in Thai essential drug list that have the same indications as your study drug?
ANS Other drugs In Thai Essential drug list, Imatinibmesilate (2) was indicated for Chronic
myelogenous leukemia (CML) in chronic stable phase.
3. What is the price of your study drug per one course as compare to the existing standard treatment?
1. ANS The cost of bosutinib is 3,437 (128,445 baht) for 1 pack of 28 500 mg tablets, with an average
cost of 122.74 (4,587 baht) for 500 mg/day (all costs exclude VAT)escalation of up to 600 mg is
permitted if; a complete haematological response has not occurred by week 8 (256,872 baht)
a complete cytogenetic response by week 12 (385,308 baht).Treatment should continue until disease
progression or until bosutinib is no longer tolerated. The trial cited in the manufacturers submission,
Study 200, indicated an average length of a course of treatment of 8.3 months; this gives an estimated
cost of treatment of 31,000 (1,158,509 baht) per patient assuming the recommended dose of
500mg/day.
Reference: http://www.nice.org.uk/guidance/ta299/resources/ta299-leukaemia-chronic-myeloidbosutinib-costing-statement2
The cost of imatinib mesilate (100mg) is 54,998.00 baht for 60 tablets/box and 109,996.00 baht
for 400mg of 30 tablets/box with the average cost of 3,667 baht for 400 mg/day. The recommended dose
is 400 mg/day.Treatment should be consider alternative choice when; patient did not complete
hematologic response within 6 months (659,976 baht); and patient did not complete cytogenetic
response within 18 months (1,979,928 baht).
Reference: durg.fda.moph.go.th:81/nlem.in.th/search?keyword=imatinib

4. What is the outstanding point of your study drug?

ANS Bosutinib acts as a dual inhibitor of Src and ABL kinases. BCR-ABL fusion gene product is a
constitutively activated tyrosine kinase which is important for the development of chronic myeloid
leukemia (CML), is highly sensitive to bosutinib. Moreover lower concentrations of bosutinib are required
to ablate BCR-ABL phosphorylation when compared to the first-generation tyrosine kinase inhibitor
imatinib. Remarkably, bosutinib has been found to be capable for imatinib-resistant BCR-ABL mutations.
It has the potency to induce deep and fast responses in second- and third-/fourth-line treatment, and the
drug has been use in who are not considered imatinib, nilotinib, and dasatinib as appropriate treatment
options. Adverts events with bosutinib were temporally and could be managed with dose modification
and not life-threatening. The most common side effect associated with gastrointestinal tract.

Study Endpoints
Safety profile
Tolerability
Pharmacokinetics of different dose
Complete cytogenic response (CCyR)
Major molecular response (MMR)
Major cytogenic response
Complete hematologic response (CHR)
Venous blood samples (pharmacokinetic parameters)
12-lead ECG
o rhythm
o heart rate (HR)
o PR interval

o QRS complex interval

o QT interval
- Population-specific QT correction (QTcN)
- Individual QT correction (QTcI)
QTcF
Standard Bazett QT correction (QTcB)
Adverse events
Safety
Tolerability
Pharmacokinetics
Primary endpoints

CCyR at 12 months

QTcN; to compare the baseline-adjusted QTc for bosutinib vs. placebo and bosutinib plus

ketoconazole vs. placebo plus ketoconazole

Tolerated dose under fed and fasted condition

Members
1. Tamakorn

Tiacharoen

ID: 533150092-1

2. Piyamaporn Uttaranakorn

ID: 533150096-3

3. Pornprapa

Panida Direkpok

ID: 533150100-8

4. Sarat

Kaewmulniem

ID: 533150134-1

5. Nudee

Chaleechiangpin

ID: 533150170-7

6. Kantisa

Boonserm

ID: 533150257-5

7. Sunisa

Klaichanthong

ID: 533150260-6

8. Hongkamon Sawangsiriwan

ID: 533150261-4