CHEMOTHERAPY(DRUGS AND TREATMENT OF DIFFERENT CANCER)

BASIC PHARMACOLOGY OF CANCER CHEMOTHERAPEUTIC DRUGS

                                               

 Anticancer Drugs(1)

Cytotoxic Drugs(1)

1. Alkylating Agents
2. Platinum Analogs
3. Antimetabolites

• Alkylating Agents

1. Nitrogen Mustards
2. Ethylenime(Thiopeta&Altretamine)
3. Alkylsulfonate(Busulfan)
4. Nitrosureas(Carmustine,Lomustine&Semustine)
5. Triazine(Dacarbazine&Temozolomide)
6. Methyl Hydrazine(Procarbazine) 

Nitrogen Mustards

1. Cyclophosphamide
2. Mechlorethamine
3. chlorambucil
4. Melphalan
5. Ifosphamide
6. Bendamustine

MECHANISM OF ACTION(Common for all alkylyting agents)

                                    

RESISTANCE

• Increased expression and activity of DNA REPAIR ENZYMES
• Decreased cellular transport of alkylating drug

ADVERSE EFFECTS

 Generally chemo drugs have two types of toxicity ACUTE and DELAYED toxicity

• Acute Toxicity
• Nausea and vomiting(Common for every drug)

Delayed Toxicity

• Myelosuppression

PLATINUM ANALOGS

1st Generation

Cisplatin

2nd Generation

Carboplatin

3rd Generation

Oxaliplatin

MOA

                                     

ADVERSE EFFECTS 

Sam as above alkylating agents

ANTIMETABOLITES

ANTIFOLATES&PURINE ANTAGONISTS

ANTIFOLATES

Methotrexate

Pemetrexed

PURINE ANTAGONISTS

1. 6-Mercaptopurine
2. 6-Thioguanine
3. Azathioprine
4. Fludarabine

BOTH MOA

                                

PYRIMIDINE ANTAGONISTS

1. 5-Fluorouracil
2. Capecitabine
3. Doxyfluridine
4. Cytarabine
5. Gemcitabine

MOA

                                       

RESISTANCE

1. Decreased drug transport via the reduced folate carrier or folate receptor protien
2. Decreased formation and decreased sensitivity of receptors and protiens 

ANTICANCER DRUGS(2)

1. Microtubule Damaging Agents
2. Topoisomerase Inhibitors
3. Antibiotics

Microtubule Damaging Agents

1. Vinca Alkaloids

• Vincristine
• Vinblastine
• Vinorelbine

Topoisomerase Inhibitors 1&2

1 Inhibitors

• Topotecan
• Irinotecan

2 Inhibitors

• Etoposide

ANTIBIOTICS (ADDIMAB mnemonic)

1. Actinomycin
2. Doxorubicin
3. Daunorubicin
4. Idarubicin
5. Mitoxantrone
6. Aclarubicin
7. Bleomycins

MOA FOR ALL THERE

                                         

ANTICANCER DRUGS(3)

1. BCR-ABL TYROSINE KINASE INHIBITOR
2. EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITOR
3. ANGIOGENESIS INHIBITOR
4. PROTEASOME INHIBITOR
5. CD20 INHIBITOR

Tyrosine kinase inhibitors

1. Imatinib
2. Dasatinib
3. Nilotinib

EGFR Inhibitors

1. Gefitinib
2. Erlotinib
3. Cetuximab
4. Trastuzumab
5. Lapatinib

MOA OF BOTH THESE

                                     

ANGIOGENESIS INHIBITORS

1. Bevacizumab
2. Sunitinib
3. Sorafenib

PROTEASOME INHIBITORS

1. Bortezomib

CD20 INHIBITOR

1. Rituximab

MOA FOR ALL THREE

                                       

CHEMO DRUGS ARE HIGHLY TOXIC AND WILL HAVE N NUMBER OF SIDE EFFECTS AS WE ALL KNOW THESE DRUGS PRIMARILY INTERFERE WITH  THE FUNCTIONAL BASIC MECHANISM THAT IS WITH DNA DUE TO MANY FACTORS LIKE GENETIC INSTABILITY DRUG RESISTANCE IS THE BIGGEST PROBLEM AND MOREOVER THE SIDE EFFECTS THESE DRUGS CARRY NOT ONLY EFFECTS US PHYSICALLY BUT ALSO MENTALLY BUT CANCER IS ONE SUCH DISEASE WHERE WE HAVE TO CONSUME ALL THESE BAD EFFECTS AND JUST WORK ON SAVING THE LIFE

CLINICAL PHARMACOLOGY OF CANCER CHEMOTHERAPEUTIC DRUGS

                                     

THE LEUKEMIAS

Childhood leukemia

ALL(Acute Lymphoblastic Leukamia)

 Most Common form of cancer in children

                                            

• Children with these disease will have better prognosis 
• A subset of patients with neoplastic lymphocytes expressing surface antigenic features of T-lymphocytes has a poor prognosis
• T-cell ALL express high level of the enzyme ADENOSINE DEAMINASE(ADA)
• This led to interest in the use of the ADA -inhibitor PENTOSTATIN(deoxycoformycin)of such t cell cases
• Until 1948 the median length of survival in ALL was 3 months
• With the advent of methotrexate the length of survival increased dramatically along with other corticosteriods and other chemo drugs 
• A COMBINATION OF VINCRISTINE AND PREDNISONE IS HIGHLY EFFECTIVE 
• More than 90% of children enter complete remission with this therapy with only minimal toxicity
• Circulating leukemic cells also travel to brain and testes 
•  When these cells travel to CNS the cancer have  high chance of relapse 
• Intrathecal therapy with methotrexate should therefore be considered as a standard component of the induction regimen for children with ALL

ADULT LEUKEMIA

• AML(acute myelogenous leukemia)

  Most common in ADULTS
• THE SINGLE MOST ACTIVE AGENT FOR AML IS CYTRABINE
• Complete remissions in about 70% of patients
• Effective combination of CYTRABINE and IDARUBICIN is also preffered
• Patients often require intensive supportive care during the period of chemo
• Such as PLATELET TRANSFUSIONS TO PREVENT BLEEDING
• Also give( FILGRASTIM) Granulocyte colony stimulating factor to shorten periods of NEUTROPENIA and ANTIBIOTICS to combat infections
• Younger patients(Age <55) can have allogeneic BONE MARROW TRANSPLANTATION( should have an HLA matched donor)                                                                             
• This procedure is preceded by high dose chemo and TOTAL BODY IRRADIATION 

CHRONIC MYELOGENOUS LEUKEMIA

                                                   

 

Balanced translocation between the long arms of Chromosomes 9 and 22 t(9:22) is observed in 90-95% cases

• Translocation results in constitutive expression of BCR-ABL fusion oncoprotien
• CLINICAL SYMPTOMS 
• Increased  WBC 
• GOAL of the treatment 
• reduce granulocytes to normal
• raise Hb concentration
• when BCR-ABL comes there comes a drug in our mind which is IMATINIB considered as standard first line therapy
• 40 to 50% patients show complete cytogeneic response 
• this drug is generally well tolerated and with minor toxicity 

CHRONIC LYMPHOCYTIC LEUKEMIA

                                                   

CHLORAMBUCIL &CYCLOPHOSPHAMIDE are the two most widely used alkylating agents for this 

• Combination of cyclophosphamide+vincristine+prednisone is also preffered
• BENDAMUSTINE is the new drug approved for the treatment of this disease either as a monotherapy or with prednisone
• PURINE NUCLEOSIDE analog FLUDARABINE is also much effective
• In relapsed or refractory disease MONOCLONAL AB are used RITUXIMAB is an anti -CD20 AB that has documented clinical activity in this setting
• OFATUMUMAB is a fully IgG1 AB that binds to a different CD20 epitope than rituximab ........Maintains activity in rituximab resistant tumors and presently approved for CLL

                                       THANKYOU