• Protocol directed 
• Adjust for the most specific diagnosis 
• Offer when clinical trials are accessable and needed 

• Cytotoxic chemo (2 or more agents in combination)
• Specific molecular targets
• Block transcription factors
• Tyrosine kinase inhibitors
• Cyto-differentiating agents
• Anti-angiogenic agents 
• Immmune modulators (active and passive)
• Hormonal agents 
• Marrow/stem cell transplantations (auto vs allogenic) 

• Methotrexate (MTX)
• Mercaptopurine (6-MP)
• Thioguanine (6-TG)
• Cytarabine (Ara-C)
• Cladribine (2-CdA) 

***These are all cycle specific for the S-phase***

Methotrexate 

MOA

Drug interactions

MOA:  

• Interferes with folate metabolism
• Polyglutamated intra-cellular function 
• Cycle cycle specific for S-phase

Drug interactions:

• NSAIDs
• Penicillin 
• Bactrim 

• Myelosuppression
• GI problems -DLSE (mucositis, diarrhea) 
• Renal problems (prevention of alkalinization and hydration)
• Hepatitis 
• CNS 

Methotrexate overdose treatment

Treatment protocol

MOA

Leucovorin 

• Used when doses of methotrexate are > 200 mg/m2
• Provies reduced folate to cells to resume purine synthesis 
• Give doses of 5-15 mg/m2 orally (po)/IV every (q) 3-6 hours for 3-9 doses 
• Continue until levels of MTX are < 0.2 uM or per protocol 
• doses of > 25 mg MUST be given IV 

Mercaptopurine 

MOA

Toxicity 

MOA:

• Incorporated into DNA and RNA
• Blocks synthesis (S-phase)

Thioguanine

MOA

Toxicity

MOA:

• Incorporates into DNA and RNA
• Blocks purine synthesis (S-phase)

Toxicity:

• Myelosuppression (DLSE) 
• GI (mild) 
• Hepatitis (rare) 

Cytarabine 

MOA

Cytarabine 

Toxicity

• Myelosuppression
• Skin (palmar-plantar erythema 
• Hepatitis
• GI (mucositis, diarrhea) 
• CNS (confusion, seizures, tremors)
• Ocular (conjunctivitis w/higher doses) 
• Fever 
• Malaise 

• Cyclophosphamide (CTX)
• Ifosfamide (IFX, ifos)
• Cisplatin (CDDP)
• Carboplatin (CBDCA)

***These are non-cell cycle specific***

Cyclophosphamide 

MOA

• Cross-linking alkylation 
• Non-cell cycle specific 

Cyclophosphamide 

Toxicity

• Hemorrhagic cystitis (MESNA, hydration) 
• GI
• SIADH (furosemide and NS) 
• Cardiac (with doses > 100 mg/kg)
• Meylosuppression (DLSE)
• Secondary leukemia 

Ifosfamide 

MOA

• Cross-linking alkylation
• Non-cell cycle specific 

Ifosfamide 

Toxicity

• Hemorrhagic cystitis (DLSE, MESNA, hydration)
• Renal (electrolyte wasting) 
• CNS
• Myelosuppression
• GI 

Cisplatin 

MOA

• Cross-linking platination
• Non-cycle specific 

Cisplatin 

Toxicity 

• Renal (DLSE, hydration, mannitol, amifostine, electrolyte wasting)
• GI (n/v delayed)
• Neurotoxicity (peripheral neuropathy, hearing loss)
• Myelosuppression 

Anthracyclines:

• Doxorubicin 
• Daunorubicin 
• Idarubicin 
• Mitoxantrone 

Doxorubicin

MOA

• Intercalation b/t base pairs in DNA double helix 
• Free radical generation 
• Forms complexes w/ iron or copper (which might explain the cardiac toxicity-dexrazoxane)
• Inhibition of topoisomerase-I and II

***non-cell cycle specific***

Doxorubicin 

Toxicity

• Myelosuppression (DLSE)
• Vesicant (dexrazoxone and cool compress) 
• Cardiac (cardiomyopathy)
• Radiosensitizer (radiation recall)
• GI (mucositis)

Bleomycin

dosage protocol

Usage

• 1 unit = 1 mg
• Maximal lifetime dose = 400 units 
• Used for causing sclerosis:  60-240 units are placed w/in the cavity...may add lidocaine to reduce local discomfort

• Cardiovascular (raynaud's phenomenon) 
• Dermatologic:  Palmar and plantar erythema, desquamation, hyperpigmentation
• Mucositis 
• Pulmonary fibrosis 
• Fever, chills, confusion, anaphylaxis (delayed several hours) 

***Aka camptothecin***

MOA:

• Inhibition of topoisomerase-I

Irinotecan (camptothecin) 

Side effects

Management of SE 

Diarrhea:

• Early diarrhea (during infusion or several hours after): Give either atropine or loperamide 
• Late diarrhea (> 24 hours after infusion):  Give either loperamide or octreotide 

Plant alkaloids 

• Vincristine (VCR)
• Etoposide (VP-16)
• Teniposide (VM-26) 

***These are cell cycle specific***

Vincristine 

MOA

• Derived from periwinkle plant
• Inhibition of mitosis by binding to tubulin in the S-phase 

Vincristine 

Toxicity

• Neurotoxicity (DLSE, jaw pain, foot drop, constipation, parayltic ileus) 
• Lethal if given IT (ascending paralysis + death) 
• Vesicant (warm compress and notify doctor) 

Etoposide 

MOA

• Topoisomerase-II inhibitor 
• Cell-cycle specific 

• Myelosuppression (DLSE)
• GI (mucositis w/higher doses) 
• Anaphylaxis 
• Irritant if extravasated
• Hypotension (infusion rate related)
• Secondary malignancies 

Asparaginase 

MOA

• Enzyme that acts indirectly to inhibit protein synthesis in certain tumor cells
• Depends on exogenous asparagine, which is a non-essential amino acid in humans 

• E. coli 
• Erwinia 
• Pegaspargase 

Asparaginase 

Toxicity

• Anaphylaxis 
• Pancreatitis
• Coagulopathy 
• GI (mild) 

Rituximab 

MOA

Dose

MOA:

•  Anti-CD20 monoclonal Ab
• Binds to CD20 on B-lymphocytes which activates complement-dependent cytotoxicity 

Rituximab 

Toxicity

• Infusion related:  Bronchospasm and hypotension.  Fever and chills 
• Luekopenia
• Consider pre-med w/acetaminophen and diphenhydramine 
• Administration rate will depend on protocol 

Imatinib 

MOA

• Inhibition of BCR-ABL tyrosine kinase 
• Blocks proliferation and induces apoptosis in BCR-ABL positive cell lines

Dose for imatinib

Availabilit

• Dose = 260 mg/m2/day (may go up to 340)
• Round dose to the nearest 50 mg

Available in dosease of 100mg or 400 mg tablets

• Fatigue/dizziness/insomnia
• Rash 
• Itching
• Fluid retention (edema, ansarca, ascites, effusions, pulmonary edema) 
• Muscle cramps, arthralgias, myalgias