CTX

Question 1

Group in which cyclophosphamide belongs

Answer 1

Alkylating agents, nitrogen mustard analog

Question 2

Mechanism of action of ctx

Answer 2

Cell cycle non specific
Bifurcation all electrophiles
Attaches to N 7 position of guanine and causes inter stand DNA breakages

Question 3

Metabolism of ctx

Answer 3

Liver by microsomes oxidases
Cytochrome P450 enzymes
Ctx is a prodrug and forms 4 hydroxy ctx which is in equilibrium with aldophosphamide and it undergoes oxidation with aldehyde dehydrogenase to form inactive metabolites .
Aldophosphamide form active metabolite phospharamide mustard and acrolein (urotoxic)

Question 4

Route of ctx

Answer 4

Oral and Iv

Question 5

Distribution of ctx

Answer 5

20% of ctx protein bound , 60% of metabolites are protein bound
Distribution in brain and csf

Question 6

Elimination of ctx

Answer 6

20% urine
4% bile

Question 7

Dose reduction of ctx

Answer 7

In renal and hepatic impairment

Question 8

Indications of ctx

Answer 8

Breast
NHL
Cll
Ovarian
Sts
Neuroblastoma and wilms

Question 9

Dose of ctx

Answer 9

10-15 mg per kg for 10

Breast 600 mg per m2 every 3 weekly in ac regimen

NHL : 400 to 600 mg per m2 every 21 days

Oral 1 to 5 mg per kg per day every day for initial and maintence dosing

Question 10

Toxicity of ctx

Answer 10

Myelosuppression dose limiting
Bladder toxicity
Nause/ vomiiting
Amenorrhea/ sterility
Cardiotoxicityincreasing with doxorubicin, trastuzumab and chest rt
Immunosuppression requiring prophylactic antivirals, fungal and antibiotics
Second malignancy
Alopecia after 2-3 weeks and hyperpigmentation of skin and nails
Pregnancy cat d
Venocuulisive disease
Potent emetogenic after 1500 mg per m2
SIADH like syndrome causing hyponatremia

Question 11

Treatment for myelosuppression in ctx

Answer 11

Pancytopenia
Netutropenia specially
Stop treatment if neutrophils less than 1500 and platelets less than 50 thousand
Primary and secondary prophylaxis with g csf is needed

Question 12

Urotoxicity of ctx

Answer 12

Aggressive hydration
Mesna
Check rbc in urine
Discontinue treatment with ctx if severe hemorrhagic cystitis

Question 13

Can you give ctx with tamoxifen and y.?

Answer 13

Increased increased risk of thromboembolic events

Question 14

Storage

Answer 14

Below 25 degree celcisum , use immediately after reconstitution

Question 15

How to reconstitute ctx

Answer 15

With normal saline or distilled water
For dilution of reconstituted solution use 5 % dextrose

Question 16

How does metabolism occur and half life

Answer 16

Ctx is an enzyme inducer and induced it’s own metabolism
Half life is 2 to 8 hrs

Question 17

Emetogenic potential

Answer 17

Moderate risk at 1500 mg per m2
High risk after 1500 mg per m2

So combo of dexa odansetron and aprepitant is used

Question 18

When to administer ctx

Answer 18

Morning

Question 19

Other uses and doses

Answer 19

Multiple myeloma : 300 mg per m2 ORAL on day 1, 8,15, 22 of 28 day cycle

ALL : 1200 mg/ m2 IV on day 1 of 28 day cycle

HyperCVAD IN ALL : 300 mg per m2 IV Q12 HRS DAY 1 TO 3