This document discusses cytotoxic drugs used in chemotherapy. It begins by defining cytotoxic agents as drugs that destroy or inhibit the growth of malignant cells. It then provides details on various classes of cytotoxic drugs including alkylating agents, platinum coordination complexes, antimetabolites, topoisomerase inhibitors, antibiotics, and targeted therapies. For each drug class and individual drugs, it describes mechanisms of action, indications, dosages, administration routes, metabolism, toxicities and resistance mechanisms. The document provides an in-depth review of cytotoxic chemotherapy agents.

1. CYTOTOXIC DRUGS
DR. Apurva Pandey
M.D Radiation Oncology

2. CHEMOTHERAPY
 Cytotoxic agents - destroy or inhibit growth and division of malignant
cells in the treatment of cancer
 Paul Ehrlich coined the term ‘chemotherapy’ in 1908
Used for :
 primary induction treatment
 neoadjuvant treatment
 adjuvant treatment
 direct instillation

3. GENERAL PRINCIPLES IN
CHEMOTHERAPY
1.The malignant cell viewed as an invader
(a) selectivity of drugs is limited
(b) Infecting microorganisms are amenable to
immunological and other host defence mechanisms
 absent or minimal against cancer cells.
2. Survival time is related to the number of cells
that escape chemotherapeutic attack
3. subpopulations of cells differ in their rate of
proliferation and susceptibility to cytotoxic drugs.
4. combined modality approach
5. maximum tolerated doses
6.Synergistic combinations and rational sequences
(a) Drugs which are effective when used alone.
(b) Drugs with different mechanisms of action.
(c) Drugs with differing toxicities.
(d) Empirically by trial and error; optimal schedules are
mostly developed by this procedure.
(e) Drugs with different mechanisms of resistance.
(f) Drugs with known synergistic biochemical
interactions.
(g) Kinetic scheduling

4. Cytotoxic drugs are either cell cycle nonspecific (CCNS) or cell cycle specific (CCS).
(a) Cell cycle nonspecific: kill resting as well as dividing cells
(b) Cell cycle specific: kill only actively dividing cells.

5. (a) Cell cycle nonspecific: kill resting as well as dividing cells, e.g
cyclophosphamide, chlorambucil, dacarbazine,cisplatin, procarbazine,
actinomycin D.
(b) Cell cycle specific: kill only actively dividing cells.
 Their toxicity is generally expressed in S phase.
 These drugs may show considerable phase selectivity, e.g.—
 G1: Vinblastine.
 S : Mtx, cytarabine, fludarabine, 6-TG, 6-MP, 5-FU, hydroxyurea, mitomycin C,
doxorubicin, daunorubicin.
 G2: Daunorubicin, bleomycin, etoposide, topotecan.
 M: Vincristine, vinblastine, vinorelbine, paclitaxel, docetaxel.

6. CLASSIFICATION OF CYTOTOXIC
DRUGS
ALKYLATING AGENTS
PLATINUM CO-ORDINATION COMPLEXES
ANTI-METABOLITES
TOPO-ISOMERASE -2 INHIBITORS
ANTI-BIOTICS
MISCELLANEOUS
TARGETED DRUGS
HORMONAL DRUGS

7. ALKYLATING
AGENTS
• NITROGEN
MUSTARDS:
mechlorethamin
e,
cyclophosphami
de, ifosfamide,
chlorambucil,
melphalan
• ETHYLENIMINE:
thio-TEPA
• ALKYLSULFONAT
ES: busulfan
• NITROSOUREAS:
carmustine
(BCNU),
lomustine
(CCNU)
• TRIAZINE:
dacarbazine,
temozolamide
• METHYL-
HYDRAZINE:
procarbazine
PLATINUM
CO-
ORDINATION
COMPLEXES
• CISPLATIN
• CARBOPLATIN
• OXALIPLATIN
ANTI-
METABOLITES
• FOLATE
ANTAGONIST:
methotrexate,
pemetrexed
• PURINE
ANTAGONIST:
6-
mercaptopurine,
6-thioguanine,
azathioprine,
fludarabine
• PYRIMIDINE
ANTAGONIST:
5-FU,
capecitabine,
cytarabine
• MICROTUBULE
DAMAGING
AGENTS:
vincristine,
vinblastine,
vinorelbine,
paclitaxel,
docetaxel,
estramustine
TOPO-
ISOMERASE -
2 INHIBITORS
• ETOPOSIDE
ANTI-BIOTICS
• ACTINOMYCIN
• DOXORUBICIN
• DAUNORUBICIN
• EPIRUBICIN
• MITOXANTRON
E
• BLEOMYCIN
• MITOMYCIN C
MISCELLANEOUS
• HYDROXYUREA
• L-asparaginase
• TRETINOIN
• ARSENIC
TRIOXIDE

8. TARGETED DRUGS
• TYROSINE KINASE INHIBITORS:
imatinib, nilotinib
• EGF RECEPTOR INHIBITORS:
geftinib, erlotinib, cetuximab
• ANGIOGENESIS INHIBITORS:
bevacizumab, sunitinib
• PROTEOSOME INHIBITORS:
bortezomib
• UNARMED MONOCLONAL ANTIBODY:
rituximab, trastuzumab
HORMONAL DRUGS
• GLUCOCORTICOIDS
• ESTROGENS:
fosfestrol, ethinylestradiol
• SELECTIVE ESTROGEN RECEPTORS
MODULATOR:
tamoxifen, toremifene
• SELECTIVE ESTROGEN RECEPTOR
DOWN REGULATOR: fulvestrant
• AROMATASE INHIBITOR:
letrozole, anastrozole, exemestane
• ANTIANDROGEN:
flutamide, bicalutamide
• 5-α REDUCTASE INHIBITOR: dutasteride
• GnRH ANALOGUES:
nafarelin, leuprorelin, triptorelin
• PROGESTINS: hydroxyprogesterone
acetate etc.

9. ALKYLATING AGENTS
 first anticancer molecules
 vesicant properties of mustard gas used during World War I were shown to be
accompanied by the suppression of lymphoid and hematologic functions in
experimental animals and led to the development of mechlorethamine as the
first alkylating agent used in the management of human cancer.

10. alkyl group
binds to
one site of
nucleophil
es
repair
enzymes
cause DNA
fragmentatio
n by
identifying
the site
repair
leading
to
formatio
n of
abnormal
base
pairs
CELL DEATH
alkyl
group
binds to
two sites
CROSS-
LINKING of
two bases
by
covalent
bonds
preventio
n of DNA
replicatio
n or
transcripti
on
MECHANISM OF ACTION

11. MECHLORETHAMINE
 original nitrogen mustard
 ABSORPTION
 not orally bioavailable
 MECHANISM OF RESISTANCE
 decreased cellular uptake
 increased inactivation by increased expression of
sulfhydryl proteins
 enhanced DNA repair mechanism
 METABOLISM
 rapid hydrolysis in plasma to active metabolites
 short plasma half life 15 – 20 mins
 >50% of inactive drug excreted in urine in 24 hrs
 INDICATIONS
Hodgkin’s and Non-Hodgkin’s lymphoma
Cutaneous T-cell Lymphoma
intrapleural/ intrapericardial/ intraperitoneal treatment of
metastatic disease
 DOSAGE
MOPP regimen: 6mg/m2 IV on D1 and D8 X every 28 days
Cutaneous lymphoma: 10 mg diluted in 60mL sterile water for
topical application
Intracavitary use: 0.2-0.4 mg/kg into pleural and/or peritoneal
cavity
SPECIAL CONSIDERATIONS:
In case of extravasation  immediate instillation of 2.6% sodium
thiosulphate solution into area to neutralize active drug, ice packs for 6-
12 hrs
TOXICITY
myelosuppression  may be dose limiting wit neutropenia and
thrombocytopenia, nadirs at 7-10 days with recovery by 21 days
nausea and vomiting  may be dose limitng in some patients, starts
by 3 hours with max till 24 hrs
amenorrheoa, azoospermia, hyperuricemia, alopecia
secondary malignancies: AML with IV use, BCC with topical use

12. CYCLOPHOSPHAMIDE and IFOSFAMIDE
 cycloxan, endoxan
 inactive  activated by liver cytP450 enzyme
system to active forms : phospharamide mustard
and acrolein
 RESISTANCE
 same as mechlormethamine
 decreased expression of cyt p450 enzymes
 increased aldehyde dehydrogenase leading to
increased enzymatic detoxification
 ABSORPTION
 GI availability 90% on oral administration of
cyclophosphamide
 ifosfamide nearly 100% but IV form used
commercially as oral form is highly neurotoxic
DISTRIBUTION
cyclophosphamide: throughout body including brain and CSF, also in
milk and saliva
ifosfamide: well distributed into body tissues
METABOLISM
cyclophosphamide  in liver by cytP450
elimination half life 4 – 6 hrs
parent drug and metabolites exclusively excreted in urine
ifosfamide  activated at a four-fold slower rate than
cyclophosphamide because of lower affinity to the liver P450
system  four-fold more drug is required to produce equitoxic
antitumor effects with cyclophosphamide
half-life of the drug is 3–10 hours for standard therapy and up to 14
hours for high-dose therapy
50%–70% of the drug and its metabolites are excreted in urine

13.  INDICATIONS AND DOSAGE
 CYCLOPHOSPHAMIDE
 BREAST CANCER: orally – 100 mg/m2 PO D1-14 every 28 days, IV- 600 mg/m2 every
28 days as a part of AC or CMF regimens
 NHL : 400 – 600 mg/m2 IV on D1 every 21 days  CVP regimen
750 mg/m2 on D1 every 21 days  CHOP regimen
 High Dose Bone Marrow Transplantation: 60 mg/kg IV 2 days

14. IFOSFAMIDE
 INDICATIONS:
 Recurrent germ cell tumors
 Soft tissue sarcoma, osteogenic sarcoma
 Non-Hodgkin’s lymphoma
 Hodgkin’s lymphoma
 Non–small cell and small cell lung cancer
 Bladder cancer
 Head and neck cancer
 Cervical cancer
 Ewing’s sarcoma
 DOSAGE:
 Testicular cancer: 1200 mg/m2 IV on days 1–5 every
21 days, as part of the VeIP salvage regimen
 Soft tissue sarcoma: 2000 mg/m2 IV continuous
infusion on days 1–3 every 21 days, as part of the
MAID regimen
 Non-Hodgkin’s lymphoma: 1000 mg/m2 on days 1
and 2 every 28 days, as part of the ICE regimen
 Head and neck cancer: 1000 mg/m2 on days 1–3
every 21–28 days, as part of the TIC regimen.

15.  TOXICITIES
 hemorrhagic cystitis, dysuria and increased urinary frequency  5 – 10% of patients, may begin within 24 hrs
or several weeks
 uroprotection can be done with MESNA and hydration
 myelosuppression, mainly neutropenia  may be dose limiting
 nausea vomiting, anorexia, alopecia, hyperpigmentation of skin and nails, sterility, cardiotoxicity with high
doses
 secondary malignancies like AML, bladder cancer with chr hem cystitis
 immunosuppression
 SIADH
 hypersensitivity like rhinitis, irritation of nose and throat
 IFOSFAMIDE: may lead to neurotoxicity in the form of lethargy, confusion, seizure, cerebellar ataxia,
weakness, hallucinations, cranial nerve dysfunction, and rarely stupor and coma.
 Incidence may be higher in patients receiving high-dose therapy and in those with impaired renal
function

16. CHLORAMBUCIL
 Leukeran - Aromatic analog of nitrogen mustard
 Functions as a bifunctional alkylating agent
 ABSORPTION
 Oral bioavailability is approximately 75% when taken with food.
 Max. plasma levels are achieved within 1–2 hours after oral administration.
 Extensively bound to plasma proteins
 METABOLISM
 extensively by the liver cyt P450 system to both active and inactive forms
 eliminated by kidneys  60% of drug metabolites are excreted in urine within 24 hours
 elimination half-life is 1.5–2.5 hours for the parent drug and about 2.5–4 hours for drug metabolites
 INDICATIONS
 CLL
 Non-Hodgkin’s lymphoma, Hodgkin’s lymphoma
 Waldenstrom’s macroglobulinemia
 DOSAGE
 0.1–0.2 mg/kg PO daily for 3–6 weeks as required  initiation of therapy
 2–4 mg PO daily  maintenance therapy

17.  TOXICITIES
 Myelosuppression is dose-limiting.
 Leukopenia and thrombocytopenia observed equally  delayed and prolonged nadir at 25–30 days and
recovery by 40–45 days
 Usually reversible, but irreversible bone marrow failure can occur
 Seizures :
 Children with nephrotic syndrome and patients receiving large cumulative doses are at increased risk
 Patients with a history of seizure disorder may be especially prone to seizures
 Pulmonary fibrosis and pneumonitis are dose-related and potentially life threatening

18. MELPHALAN
 Alkeran - Classic bifunctional alkylating agent that forms inter-strand and intra-strand cross-links with DNA resulting
in inhibition of DNA synthesis and function
 Oral absorption is poor and incomplete.
 mean oral bioavailability of 60%  decreased when taken with food
 widely distributed, 80-90% plasma protein bound
 METABOLISM
 Short plasma half-life  60–90 minutes.
 No significant organ metabolism
 25%–30% of drug is excreted in urine within 24 hours after administration, with the majority of the drug being
excreted in feces (up to 50%) over 6 days
 INDICATIONS:
 Multiple myeloma
 Breast cancer
 Ovarian cancer
 High-dose chemotherapy and transplant setting
 Polycythemia vera.

19.  DOSAGE:
 Multiple myeloma: 9 mg/m2 IV on days 1–4 every 4 weeks as part of the melphalan-prednisone regimen
 Transplant setting: 140 mg/m2 as a single agent
 INTERACTIONS:
 cimetidine: decreases oral bio-availability
 steroids enhance action
 cyclosporin : increase renal toxicity
 SPECIAL CONSIDERATIONS:
 caution in renal dysfunction
 when taken orally  empty stomach for max absorption
 TOXICITIES:
 myelosuppression, prolonged and cumulative nadir at 4-6 weeks after therapy
 nausea, vomiting
 hypersensitivity, erythema at IV site, ulceration

20. ETHYLENIMINE  thio-TEPA
 tri-ethylene-triophospharamide , ethylenimine analog
 ABSORPTION
 incomplete oral absorption
 intra-vesical route also where absorption from bladder may be 10 – 100%
 INDICATIONS:
 Breast cancer
 Ovarian cancer
 Superficial transitional cell cancer of the bladder
 Hodgkin’s and non-Hodgkin’s lymphoma
 High-dose transplant setting for breast and ovarian cancer
 DOSAGE:
 Usual dose is 10–20 mg/m2 IV given every 3–4 weeks
 High-dose transplant setting: Doses range from 180 to 1100 mg/m2 IV
 Intravesical instillation: Dose for bladder instillation is 60 mg administered in 60 mL sterile water weekly for up
to 4 weeks
 TOXICITY:
 myelosuppressive, mucositis, chemical or hemorrhagic cystitis following intravesical instillation

21. ALKYLSULFONATE  BUSULFAN
 Methanesulfonate-type bifunctional alkylating agent
 Excellent oral bioavailability with peak levels in serum occurring within 2–4 hours
after administration
 Distributes rapidly in plasma with broad tissue distribution.
 Crosses the blood-brain barrier and also placental barrier
 Metabolised primarily in liver
 Metabolism may be influenced by circadian rhythm with higher clearance rates
observed in the evening, especially in younger patients.

22.  INDICATION AND DOSAGE:
 CML
 Usual dose for remission induction is 4–8 mg/day PO
 Dosing on a weight basis is 1.8 mg/m2 /day
 Maintenance dose is usually 1–3 mg/day PO
 Transplant setting
 4 mg/kg/day IV for 4 days to a total dose of 16 mg/kg.
 INTERACTIONS:
 Acetaminophen may decrease busulfan metabolism  increased liver toxicity
 Itraconazole reduces busulfan metabolism upto 20%
 Phenobarbital and phenytoin increase busulfan metabolism
 TOXICITIES:
 nausea, vomting, diarrhoea : ingestion of busulfan on an empty stomach may decrease the risk of nausea and
vomiting
 adrenal insufficiency, hepatotoxicity, insomnia, anxiety, dizziness


23. • Pulmonary symptoms like cough, dyspnea, and
fever as busulfan can cause interstitial pneumonitis
 interstitial pulmonary fibrosis is referred to as
“busulfan lung,” is a rare but severe side effect of
therapy.
• May occur 1–10 years after discontinuation of
therapy

24. NITROSOUREA
 CARMUSTINE
 lipid-soluble drug with broad tissue distribution. Crosses the blood-brain barrier, reaching
concentrations >50% of those in plasma
 metabolized in urine, approx 60%–70% of drug is excreted in urine in its metabolite form,
while 10% is excreted as respiratory CO2.
 short serum half-life of only 15–20 minutes
 INDICATIONS:
 Brain tumors—Glioblastoma multiforme, brain stem glioma, medulloblastoma, astrocytoma,
and ependymoma
 Hodgkin’s lymphoma and Non-Hodgkin’s lymphoma
 Multiple myeloma
 Glioblastoma multiforme—Implantable BCNU-impregnated wafer (Gliadel)

25.  DOSAGE:
 Usual dose is 200 mg/m2 IV every 6 weeks
 Dose can sometimes be divided over 2 days
 Higher doses (450–600 mg/m2) are used with stem cell rescue
 Implantable BCNU-impregnated wafers– upto eight wafers are placed into the
surgical resection site after excision of the primary brain tumor.
 SPECIAL CONSIDERATIONS:
 causes intense pain and burning at the site of injection
 baseline PFTs, CBC should be done and monitored
 TOXICITIES:
 myelosuppression
 nausea, vomting
 pulmonary toxicity uncommon at low doses, can occur at cumulative dose >1400 mg/m2
 facial flushing and burning at IV site

26. TRIAZINE
 DACARBAZINE
 While the precise mechanism of cytotoxicity is unclear, this drug methylates
nucleic acids and inhibits DNA, RNA, and protein synthesis.
 Volume of distribution exceeds total body water content, and drug is widely
distributed in body tissues
 Metabolized in the liver by the microsomal P450 system to active metabolites
(MTIC, AIC)

27.  INDICATIONS:
 Metastatic malignant melanoma
 Hodgkin’s lymphoma
 Soft tissue sarcomas
 Neuroblastoma
 DOSAGE:
 Hodgkin’s lymphoma—375 mg/m2 IV on days 1 and 15 every 28 days, as part of the ABVD regimen
 Melanoma—220 mg/m2 IV on days 1–3 and days 22–24 every 6 weeks, as part of the Dartmouth regimen.
 As a single agent, 250 mg/m2 IV for 5 days or 800–1000 mg/m2 IV every 3 weeks
 INTERACTIONS:
 Heparin, lidocaine, and hydrocortisone—Incompatible with dacarbazine
 TOXICITIES:
 Nausea and vomiting can be severe, usually occurring within 1–3 hours and lasting for up to 12 hours. Aggressive
antiemetic therapy recommended
 Flu-like symptoms like fever, chills, malaise, myalgia, arthralgia
 CNS toxicity in the form of paresthesias, neuropathies, ataxia, lethargy, headache, confusion, and seizures
 photosensitivity

28. TEMOZOLAMIDE
 Metabolic activation to the reactive compound MTIC (3-methyl-(triazen-
1-yl) imidazole-4-carboxamide) is required for antitumor activity.
 This drug methylates guanine residues in DNA and inhibits DNA, RNA, and
protein synthesis
 Widely distributed in body tissues  oral bioavailability 100%
 Food reduces the rate and extent of drug absorption
 As it is lipophilic  it crosses the blood-brain barrier.
 Levels in brain and CSF are 30%–40% of those achieved in plasma.

29.  INDICATIONS:
 FDA-approved for refractory anaplastic astrocytomas at first relapse following treatment
with a nitrosourea and procarbazine-containing regimen
 FDA-approved for newly diagnosed glioblastoma multiforme (GBM) in combination with
radiotherapy and then as maintenance treatment.
 Metastatic melanoma
 DOSAGE:
 Usual dose is 150 mg/m2 PO daily for 5 days every 28 days
 If nadir of ANC is acceptable, the dose may be increased to 200 mg/m2 PO daily for 5
days.
 If ANC falls below acceptable levels during any cycle, the next dose should be reduced by
50 mg/m2 PO daily
 TOXICITIES:
 myelosuppression
 emetogenic
 patients should be monitored for the development of PCP
 headache, fatigue, photosensitivity

30. GBM
 Temozolomide is given at 75 mg/m2 PO daily for 42 days along with
radiotherapy (60 Gy in 30 fractions) for newly diagnosed GBM.
 During the maintenance phase, which is started 4 weeks after completion of
the combined modality therapy, temozolomide is given on cycle 1 at 150
mg/m2 PO daily for 5 days followed by 23 days without treatment.
 For cycles 2–6, the dose of temozolomide may be escalated to 200 mg/m2 if
tolerated.

31. METHYLHYDRAZINE
 PROCARBAZINE
 Hydrazine analog that acts as an alkylating agent. Weak monoamine oxidase (MAO)
inhibitor
 Rapid and complete absorption from the GI tract, reaching peak plasma levels
within 1 hour
 Procarbazine metabolites cross the blood-brain barrier, and peak CSF levels of
drug occur within 30–90 min after drug administration
 INDICATIONS:
 Hodgkin’s lymphoma and Non-Hodgkin’s lymphoma
 Brain tumors adjuvant and/or advanced disease
 Cutaneous T-cell lymphoma (CTCL)

32.  DOSAGE:
 Hodgkin’s lymphoma: 100 mg/m2 PO daily for 14 days, as part of MOPP regimen
 Brain tumors: 60 mg/m2 PO daily for 14 days, as part of PCV regimen
 TOXICITIES:
 Hypersensitivity reaction with pruritus, urticaria, maculopapular skin rash,
flushing, eosinophilia, and pulmonary infiltrates.
 Skin rash responds to steroid therapy, and drug treatment may be continued
 myelosuppression, nausea, vomiting
 INTERACTIONS:
 Concurrent use
 with alcohol or tyramine containing agents can result in nausea, vomiting, increased CNS
depression, hypertensive crisis, visual disturbances, and headache
 with antihistamines can result in CNS and/or respiratory depression
 with sympathomimetics and tricyclic antidepressants may result in CNS excitation,
hypertension, tremors, palpitations, and in severe cases, hypertensive crisis and/or
angina
 antidiabetic agents such as sulfonylurea compounds and insulin may potentiate
hypoglycemic effect.

33. PLATINUM COMPOUNDS
 platinum complexes exhibit antitumor activity - by Dr. Barnett Rosenberg and
colleagues in 1961
 an analysis of these products resulted in the identification of the cis-isomer of
a platinum coordination complex as the active compound

34. MECHANISM OF ACTION
bind to N7 of
guanine and
adenine
form mono-/bi-
functional
adducts
intra-strand and
inter-strand
crosslinks
impede DNA
functions
CELL DEATH

35. CISPLATIN
 Not absorbed orally.
 Widely distributed to all tissues with highest concentrations in the liver and
kidneys
 METABOLISM:
 within the cytoplasm of the cell, low concentrations of chloride (4 mM) favor
the aquation reaction whereby the chloride atom is replaced by a water
molecule, resulting in a highly reactive species
 Approximately 10%–40% of a given dose of cisplatin is excreted in the urine in
24 hours, with 35%–50% being excreted in the urine after 5 days of
administration

36.  INDICATIONS:
 Testicular cancer
 Ovarian cancer
 Bladder cancer
 Head and neck cancer
 Esophageal cancer
 Small cell and non–small cell lung cancer
 Non-Hodgkin’s lymphoma
 Trophoblastic neoplasms
DOSAGE:
• Ovarian cancer—75 mg/m2 IV on day 1 every 21 days
as part of the cisplatin/paclitaxel regimen, and 100
mg/m2 on day 1 every 21 days as part of the
cisplatin/cyclophosphamide regimen.
• Testicular cancer—20 mg/m2 IV on days 1–5 every 21
days as part of the PEB regimen
• Non–small cell lung cancer—60–100 mg/m2 IV on day 1
every 21 days as part of the cisplatin/etoposide or
cisplatin/gemcitabine regimens
Toxicities –
• Nephrotoxicity  Dose-limiting toxicity in up to 35%–
40% of patients.
• Electrolyte abnormalities, mainly hypomagnesemia,
hypocalcemia, and hypokalemia, are common.
Hyperuricemia rarely occurs
• emetogenic agent
• Paresthesias and numbness in a classic stocking-glove
pattern
• Ototoxicity
• Hypersensitivity reactions

37. CARBOPLATIN
 not absorbed orally
 widely distributed, crosses BBB
 does not undergo significant metabolism
 INDICATIONS:
 Ovarian cancer
 Germ cell tumors
 Head and neck cancer
 Small cell and non–small cell lung cancer
 Bladder cancer
 Relapsed and refractory acute leukemia
 Endometrial cancer.
Dosage –
• Dose of carboplatin is usually calculated to a target
area under the curve (AUC) based on the glomerular
filtration rate (GFR)
Calvert formula is used to calculate dose  Total dose
(mg) = (target AUC) X (GFR + 25). Note: Dose is in mg
NOT mg/m2
Target AUC is usually between 5 and 7 mg/mL/min for
previously untreated patients.
In previously treated patients, lower AUCs (between 4
and 6 mg/mL/min) are recommended
marrow/stem cell transplant setting
Doses up to 1600 mg/m2 divided over several days.
TOXICITIES
Myelosuppression ,nausea, vomiting : may be delayed
renal toxicities ,peripheral neuropathies and allergic
reaction

38. OXALIPLATIN
 Third-generation platinum compound.
 Widely distributed to all tissues with a 50-
fold higher volume of distribution than
cisplatin.
 INDICATIONS:
 Metastatic colorectal cancer—FDA-approved
in combination with infusional 5-FU/LV in
patients with advanced, metastatic disease.
 Early-stage colon cancer—FDA-approved as
adjuvant therapy in combination with
infusional 5-FU/LV in patients with stage III
colon cancer and also effective in patients
with high-risk stage II disease
 Metastatic pancreatic cancer
 Metastatic gastric cancer and
gastroesophageal cancer
• DOSAGE:
• Recommended dose is 85 mg/m2 IV over 2 hours, on an
every 2-week schedule.
• Can also administer 100–130 mg/m2 IV on an every 3-
week schedule.
• Diluted with 5% dextrose solution as is more stable in
dextrose solution than NS
• oxaliplatin infusion should precede 5-FU infusion when
given together as it may be partially degraded.
TOXICITIES:
NEUROTOXICITY:
Acute toxicity is seen in up to 80%–85% of patients  a peripheral sensory
neuropathy with distal paresthesia and visual and voice changes, often
triggered or exacerbated by cold.
Dysesthesias in the upper extremities and laryngopharyngeal region with
episodes of difficulty breathing or swallowing are also observed usually
within hours or 1–3 days after therapy
Chronic toxicity is dose-dependent with a 15% and >50% risk of
impairment in proprioception and neurosensory function at cumulative
doses of 850 and 1200 mg/m2, respectively nausea, vomiting, diarrhoea,
hepatotoxicity,

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