Chemotherapy classes for more lectures please contact Dr. Salah Mabrouk Khallaf MD Medical Oncology & BMT South Egypt Cancer Institute Email: salahmab76@yahoo.com

1. By
Salah Mabruok Khalaf
South Egypt Cancer Institute
2013
Clinical Pharmacy
Medical Oncology course
ChemotherapyChemotherapy: TopoisomeraseTopoisomerase
inhibitorsinhibitors

2. Classification of Chemotherapeutic AgentsClassification of Chemotherapeutic Agents
• Alkylating AgentsAlkylating Agents AntimetabolitesAntimetabolites:
• Antitumor AntibioticsAntitumor Antibiotics Anti-microtubulesAnti-microtubules:
• Topoisomerase inhibitorsTopoisomerase inhibitors:
– Topoisomerase I inhibitorsTopoisomerase I inhibitors
• Camptothecin: Topotecan, Etoposide
– Topoisomerase II inhibitorsTopoisomerase II inhibitors
• Anthracyclines
• Epipodophyllotoxin: Irinotecan, topotecan
• Miscellaneous:

3. DNA topoisomerases
• These are enzymes that alter DNA topology by
causing and resealing DNA strand breaks.
Topoisomerases bind to DNA domains, forming
a “cleavable complex,” which allows DNA to
unwind in preparation for cell division.
• Topoisomerase I relaxes supercoiled single-
stranded DNA.
• Topoisomerase II catalyzes the double-
stranded breaking and resealing of DNA

4. Irinotecan
Indications
1. Colorectal cancer
2. Lung cancer
3. Pancreatic Cancer
4. Ovarian Cancer
Form
– 100-mg vials

5. Irinotecan
• Dose
– Start at 125 mg/m2 IV weekly for 4 weeks followed by
a 2-week rest.
• Dose modification.
– Use with caution for hepatic insufficiency

6. Irinotecan
Administration
• Administer as a 90-minute infusion.
– If diarrhea, abdominal cramps (mostly cholinergic in
nature) develops during the infusion of the drug,
administer atropine, 0.25 to 1.0 mg IV.
– For the first poorly formed stool preceding delayed
diarrhea, administer loperamide (Imodium), 4 mg PO,
then 2 mg every 2 hours (4 mg PO every 4 hours at
night) until the patient is free of diarrhea for 12 hours.

7. Irinotecan
Administration
• If administered in combination with fluorouracil &
leucovorin, administer leucovorin immediately
after irinotecan, & administer fluorouracil
immediately after leucovorin
– Irinotecan >>> leucovorin >>> fluorouraci
• Premedication with antiemetics (dexamethasone
plus ondansetron/granisetron) is recommended,
at least 30 min prior to infusion.

8. Irinotecan
• IV Preparation
– Dilute in D5W to a final concentration of 0.12-2.8
mg/mL (most commonly in 500 mL D5W)
– NS can be used, but precipitation under refrigeration
is more likely with NS, so D5W is generally preferred

9. Irinotecan
• Toxicity
– Dose-limiting.
• Profuse diarrhea (especially in patients 65 years of
age and older) and myelosuppression
– Common.
• Neutropenia; mild nausea, vomiting, abdominal
cramps; flushing during administration; mild
alopecia.
– Occasional.
• LFT abnormalities, headache, fever, dyspnea

10. Topotecan
Indications
1. Lung cancer
2. Ovarian Cancer
3. Cervical cancer
Form
– 4-mg vials
– 0.25- and 1-mg capsules

11. Topotecan
• Dose
– Usual dose is 1.25 mg/m2
IV over 30 minutes for 5
consecutive days every 3 weeks
– 2.3 mg/m2
PO for 5 days of 21-day cycle
• Dose modification.
– None for impaired hepatic function.
– Reduce dosage by 50% for creatinine
clearance levels of 20 to 40 mL/minute..

12. Topotecan
Administration
• IV Infusion
– Administer 1.5mg/m² by IV infusion over 30 minutes
• Capsules
– Administer 2.3mg/m² PO QD x5days; repeat at 21-day
cycles

13. Topotecan
• IV Preparation
– Reconstitute in 4 mL SWI to obtain a 1 mg/mL solution
– Dilute in 50-250 mL NS or D5W
• Storage
– Store intact vials at room temp protected from light

14. Topotecan
• Toxicity
– Dose-limiting.
• Myelosuppression
– Common.
• Nausea and vomiting; diarrhea, constipation,
abdominal pain; alopecia; headache, fatigue, fever;
arthralgias and myalgias.
– Occasional.
• Transient elevation of LFTs; paresthesia; rash;
microscopic hematuria

15. Etoposide
Indications
1. Testicular carcinoma
2. lung cancer
3. Lymphoma
4. Other malignancies
Form
– 100-mg vials
– 50mg capsules

16. Etoposide
• Dose
– 50 mg/m2
PO daily for 21 days, or
– 100 mg/m2
IV daily for 3 to 5 days, depending on
the regimen
• Dose modification
– Administer with caution in the presence of renal
dysfunction; reduce doses by 25% or 50% for
creatinine clearance levels of <50 mL/minute and
<10 mL/minute, respectively.
– Dose reduction is also recommended for patients
with abnormal liver function..

17. Etoposide
Administration
• IV Infusion
– Administer IV infusion over 30 minutes

18. Etoposide
• IV Preparation
– Concs >0.4 mg/mL are very unstable
– Lower dose regimens (<1 g/dose): doses may be diluted
in 100-1000 mL of D5W or NS
– High dose regimens (>1 g/dose): draw total dose into an
empty Viaflex container & add appropriate amount of
diluent for a final concentration of 1 mg/mL

19. Etoposide
• Toxicity
– Dose-limiting.
• Myelosuppression
– Common.
• Nausea and vomiting (with oral dosing, but
uncommon with intravenous dosing); alopecia
(usually mild); hypotension if rapidly infused;
metallic taste during drug infusion.
– Occasional.
• Anemia, thrombocytopenia, pain at injection site,
phlebitis, abnormal LFTs

20. Teniposide
Indications
Acute lymphoblastic leukemia
Form
–50-mg vials

21. Teniposide
• Dose
– 150 to 250 mg/m2
once or twice weekly
• Dose modification
– Dose reduction is recommended for patients with
abnormal liver function..

22. Teniposide
Administration
• IV Infusion
– Administer IV infusion over 30 minutes

23. Teniposide
• IV Preparation
– Must be diluted with either D5W or NS to a final
concentration of 0.1, 0.2, 0.4 or 1 mg/mL
– Administer 1 mg/mL solutions within 4 hr of preparation
to reduce potential for precipitation
– Precipitation may occur at any concentration

24. Teniposide
• Toxicity
– Dose-limiting.
• Myelosuppression
– Common.
• Hypotension with too rapid infusion
– Occasional.
• Nausea and vomiting, alopecia, abnormal LFTs,
phlebitis