chemo protocol ne

7/27/2019 CHEMO PROTOCOL newwww.pptx

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BY R ph. HUMAIRA SHAFIQIV Pharmacist at NIBD


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CONTENTS:

History Hematological Malignancy Chemo Regimens Miscellaneous regimens Case history


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HISTROY:

Early 1900s, the famous German chemist

Paul Ehrlich. (20th century).

He was the one who coined the term

chemotherapy.

In 1908, his use of the rabbit model for

syphilis led to the development of arsenicals

to treat this disease.


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Hematological Malignancies

TYPES

LEUKAEMIAS

ALL AML CLL CML

LYMPHOMAS

HODGKINLYMPHOMAS

NON-HODGKINLYMPHOMAS

MYELOMAS


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ACUTE LYMPHOBLASTIC

LEUKEMIA: (ALL) Cancer Of The White Blood Cells

Characterized By Excess Lymphoblasts.

25 Years Of Age & Peak Old Age.

Variant Features Of Alla) ALL With Cytoplasmic Granules

b) Aplastic Presentation OfALL

c) ALL With Eosinophilia

d) Relapse OfALL

e) SecondaryALL
http://en.wikipedia.org/wiki/Hematological_malignancyhttp://en.wikipedia.org/wiki/Lymphoblasthttp://en.wikipedia.org/wiki/Lymphoblasthttp://en.wikipedia.org/wiki/Hematological_malignancy


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CHRONIC LYMPHOBLASTIC

LEUKEMIA

Rapid Growth Of Immature Cells

Such Cells Are Found In The Bone Marrow,

Blood, And Other Body Tissues.

Middle-aged Adults And In Children.

Philadelphia Chromosome.


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DIFFERENCE BETWEEN ALL &

CLL

ACUTE LYMPHOBLASTICLEUKEMIA

CHRONIC LYMPHOBLASTIC

LEUKEMIA

Develop from early cells,

called "blasts".

Blasts are young cells, that

divide frequently. In acute

leukemia cells,

they don't stop dividing.

The leukemia cells come

from mature, abnormal

cells.

The cells thrive for too long

and accumulate.

The cells grow slowly.


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ACUTE MYELOID LEUKEMIA

(AML)

CancerOf The Myeloid Line Of Blood

Cells,

Rapid Growth Of Abnormal White Blood

Cells

Accumulate In The Bone Marrow

Interfere With The Production Of Normal

Blood Cells
http://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Myeloidhttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/Haematopoiesishttp://en.wikipedia.org/wiki/Haematopoiesishttp://en.wikipedia.org/wiki/Haematopoiesishttp://en.wikipedia.org/wiki/Haematopoiesishttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/White_blood_cellhttp://en.wikipedia.org/wiki/Myeloidhttp://en.wikipedia.org/wiki/Cancer


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CHRONIC MYELOID

LEUKEMIA

Leukemia cells tend to build up in thebody over time

Too many of a specific type of white

blood cell called a granulocyte.Asymptomatic.

occur in adults

start in organs such as the lungs, colon,or breast and then spread to the bonemarrow


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DIFFERENCE BETWEEN

AML/CML:

ACUTE MYELOID

LEUKEMIA

CHRONIC MYELOID

LEUKEMIA

Granulocytic, myelocytic,myeloblastic, or myeloid.

20% childhood leukemias

Over a short period of daysto weeks

Children with certaingenetic syndromes

Fanconi anemia, Bloomsyndrome, Kostmann

syndrome, and Downsyndrome.

Uncommon in children

Over a period of months

or years

Part of chromosome #9

breaks off and attaches

itself to chromosome

#22, so that there is an

exchange of genetic

material between thesetwo chromosomes.


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LYMPHOMAS:

Lymphoma Is A Disease Where The Body's

Lymphoid Tissues Develop Malignant Cells.

Type Of Cancer Involving Cells Of The

Immune System, Called Lymphocytes.

5 Subtypes OfHodgkin's Disease

30 Subtypes OfNon-hodgkin's Lymphoma.
http://www.emedicinehealth.com/script/main/art.asp?articlekey=3907http://www.emedicinehealth.com/script/main/art.asp?articlekey=3907


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TYPES OF HD

Nodular sclerosis HD.

Mixed cellularity HD.

Lymphocyte-rich HD.

Lymphocyte-depleted HD.

Nodular lymphocyte predominant HD.


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TYPES OF NHL

Aggressive (Fast-growing)

Indolent (Slow-growing)

B-cell Non-hodgkinLymphomas

a) Burkitt Lymphoma

b) CLL/SLL

c) Diffuse Large B-cellLymphoma

d) Follicular Lymphoma

e) Immunoblastic Large CellLymphoma

f) Precursor B-lymphoblasticLymphoma

g) Mantle Cell Lymphoma.

T-cell Non-hodgkinLymphomas

a) Mycosis Fungoides

b) Anaplastic Large CellLymphoma

c) Precursor T-lymphoblasticLymphoma


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DIFFERENCE B/W HN & NHN

HODGKIN DISEASE NON-HODGKIN

LYMPHOMA

Epstein-barr Virus And

Contain Reed-sternberg

Cells.

Localized In One Lymph

Node.

Surrounding Chain In The

Neck, Shoulder, And Chest.

Age Between 15 And 35

And Over 50.

Develop In Peripheral

Lymph Nodes.

Spread Throughout The B

Age 60 And Over.


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SYMP. OF HN & NHL


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MYELOMA

Also Known As Multiple Myeloma Or

Myelomatosis - Is A Cancer Of Plasma Cells.

Single Type Of Abnormal Antibody.

Para protein Or M Protein.

It Cant Fight Infection Effectively.


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TYPES OF MYELOMA:

Asymptomatic Smoldering Or Indolent

Myeloma

Increased Level Of Plasma

Cells

Elevated M-protein

NoAnemia

Monoclonal Gammopathy

Of UndeterminedSignificance (MGUS)

Symptomatic

Elevation Of Plasma Cells

M- Protein Detected In

The Blood Or Urine

Plasmacytoma.

Waldenstrom's

Macroglobulinemia.

Other Myeloma

Light Chain Myelomas

Heavy Chain Disease

Non- Secretory Myeloma.
http://lymphoma.about.com/od/glossary/g/M-Protein.htmhttp://lymphoma.about.com/od/glossary/g/anemia.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Plasmacytoma.htmhttp://adam.about.net/encyclopedia/infectiousdiseases/Macroglobulinemia-of-Waldenstrom.htmhttp://adam.about.net/encyclopedia/infectiousdiseases/Macroglobulinemia-of-Waldenstrom.htmhttp://adam.about.net/encyclopedia/infectiousdiseases/Macroglobulinemia-of-Waldenstrom.htmhttp://adam.about.net/encyclopedia/infectiousdiseases/Macroglobulinemia-of-Waldenstrom.htmhttp://adam.about.net/encyclopedia/infectiousdiseases/Macroglobulinemia-of-Waldenstrom.htmhttp://lymphoma.about.com/od/glossary/g/Plasmacytoma.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/Mgus-Monoclonal-Gammopathy-Of-Undetermined-Significance.htmhttp://lymphoma.about.com/od/glossary/g/anemia.htmhttp://lymphoma.about.com/od/glossary/g/M-Protein.htmhttp://lymphoma.about.com/od/glossary/g/M-Protein.htmhttp://lymphoma.about.com/od/glossary/g/M-Protein.htm


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SYMPTOMS:


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AML ADE/DA

Indication:Induction chemotherapy as part of the treatment of

acute myeloid leukemia (AML) in patients who

are do not enter the MRC AML 15 Trial. Pre-treatment Evaluation:

FBC.

LFT, U&E, Creatinine

Consider ECG +/- echocardiogram if clinical

suspicion of cardiac dysfunction


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DRUG REGIMEN:

DAY(S) DRUGS DOSE ROUTE COMMENTS

1 - 10 Cytarabine 100mg/m2

BD

IV IV Bolus

1 , 3 + 5 Daunorubicin 50mg/m2

OD

IV IV Infusion in100ml

0.9% NaCl over 1hr

1 - 5 Etoposide 100mg/m2

OD

IV IV Infusion in

500mls 1L

0.9% NaCl over 1hr


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Conti..

Cycle Frequency:

Two cycles of induction chemotherapy are usually

given the first for 10 days the second for 8 days.

Dose Modifications (Hepatic)

Bilirubin 20 - 50mol/l reduce daunorubicin dose by

25% and reduce etoposide dose by 50%.

Bilirubin > 50mol/l reduce daunorubicin dose by 50%

and clinical decision whether to give etoposide.

Bilirubin > 34mol/l reduce cytarabine dose by 50%.


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Dose Modifications: (Renal)

Serum creatinine 105265mol/l reduce

daunorubicin dose by 25%.

Serum creatinine > 265mol/l reducedaunorubicin dose by 50%.

CrCl 45-60 ml/min give 85% dose ofetoposide.

CrCl 30-45 ml/min give 80% dose of etoposide

CrCl 15-30 ml/min give 75% dose of etoposide CrCl < 15 ml/min give 50% dose of etoposide


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Haematological:

The second course of ADE should only

be commenced when neutrophils have

recovered to1.0 x 109/l and platelets to

100 x 109/l.Additional Modifications:

Daunorubicin maximum cumulative dose

= 600mg/m2


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Concurrent Medication:

Consider Allopurinol 300mg od PO

(100mg if creatinine clearance


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AML High Dose Cytarabine

Indication: Consolidation chemotherapy as part of the

treatment of acute myeloid leukaemia (AML)

DAY(S) DRUGS DOSE ROUTE COMMENTS1, 3 + 5 Cytarabine 1.5g/m2 BD/

3g/m2 BD

IV IV Infusion in

250mls 0.9%

NaCl over 4hrs

Cycle Frequency Two courses of chemotherapy.


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Dose Modifications:

Hepatic;

Bilirubin > 34mol/l reduce cytarabine

dose by 50%.

HAEMATOLOGICAL:

A course of Cytarabine should only be

commenced when neutrophils have

recovered to 1.0 x 109/l and platelets to100 x 109/l.


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Consider Allopurinol 300mg od PO (100mg if

creatinine clearance


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CML CVP

Indication: Follicular and other indolent lymphomas

Waldenstroms macroglobulinaemia

Chronic Lymphocytic Leukaemia Aggressive lymphoma where more intensive

chemotherapy is not indicated

Pre-treatment Evaluation:

FBC. LFT, U&E, Creatinine


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Drug Regimen:


1 Cyclophosphamide 750mg/m IV Bolus via fast running

drip of 0.9% saline.

1 Vincristine 1.4mg/m

(max 2mg)

IV In 20mls 0.9% saline

bolus injection as per

national protocol

1 - 5 Prednisolone 40mg/m PO Take in the mornings;

swallow whole with

food


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Additional Information:

Consider Vincristine 1mg for elderly

patients (>70 years)

Alternatively Cyclophosphamide may be

given as 600 mg/m PO for 5 days.

Cycle Frequency:

Repeat every 21-28 days to a maximum

clinical response.

Usually 6-8 cycles.


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Dose Modifications:Renal:

Creatinine clearance Modification

>50 100%

10-50 75% dose ofCyclophosphamide


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CONTI..

Additional Modifications:

Vincristine: If patient complains of significant constipation orsensory loss in fingers and/or toes, discuss possible dosereduction with Consultant before administration.

Previous neutropenic sepsis, discuss the use of prophylacticantibiotics and/or G-CSF support with Consultant.


Consider Allopurinol 300mg OD PO (100mg if creatinineclearance


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CLL CVP-R

Indication:

Follicular and other indolent lymphomas. Waldenstroms macroglobulinaemia.

Chronic Lymphocytic Leukaemia. Aggressive lymphoma where more intensivechemotherapy is not indicated.

Cycle Frequency:

Repeat every 21-28 days to a maximum clinical

response

Usually 6-8 cycles


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DRUG REGIMEN:


1 Rituximab 375mg/m IV

1 Cyclophosphamide 750mg/m IV Bolus via fast running

drip of 0.9% saline.


(max 2mg)


bolus injection

1 - 5 Prednisolone 40mg/m PO Take in the mornings;

swallow whole with

food.


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Additional Information:

Rituximab infusion speed: First infusion: Initiate at 50mg/h; if tolerated

increase rate at 50mg/h increments every 30

minutes to a maximum of 400mg/h.

Subsequent infusions: Initiate at 100 mg/h; iftolerated increase rate at 100mg/h increments

every 30 minutes to a maximum of 400 mg/h.

Consider Vincristine 1mg for elderly patients

(>70years) Alternatively Cyclophosphamide may be given

as750mg/m PO for 5 days.


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Additional Modifications:

Vincristine: If patient complains of significantconstipation or sensory loss in fingers and/or toes,

discuss possible dose reduction with Consultant

before administration.

Previous neutropenic sepsis, discuss the use of

prophylactic antibiotics and/or G-CSF support with

Consultant.

Rituximab

- Circulating tumour cells > 50 x 109/l consider

delay of Rituximab.- Tumour bulk; single lesion >10cm consider delay ofRituximab.


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ConsiderAllopurinol 300mg od PO (100mgif creatinine clearance


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NHL: FC-R

INDICATION:

Mantle Cell Lymphoma

Pre/post-treatment Evaluation :

FBC, LFT, U&E, Creatinine


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Drug Regimen:

DAY(S) DRUG DOSE ROUTE COMMENTS

1 Rituximab 375mg/m2 IV

1 - 3 Cyclophosphamide 250mg/m2 IV Bolus injection via

fast

running drip of0.9% NaCl

1 - 3 Fludarabine 25mg/m2 IV IV infusion in

100ml 0.9%

NaCl over 30min

Al i l ORA


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Alternatively an ORAL

schedule:DAY(S) DRUG DOSE ROUTE COMMENTS

1 - 5 Cyclophosphamide 150mg/m2 PO With breakfast

1 - 5 Fludarabine 24mg/m2 PO With lunch

Cycle Frequency Repeat every 28 days

Maximum of 6 cycles

Concurrent Medication

Allopurinol 300mg od PO (100mg if creatinine

clearance


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Dose Modifications:

Renal:

Reduce to 50% dose if renal impairment

(CrCl between 30-60ml/min)

Do not give if creatinine clearance 50 100%

10-50 75% dose of

Cyclophosphamide


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Haematology:Neutrophils x 109/l Dose Given

> 0.1 100%

< 0.1 Delay all drugs for 1 week

Platelets x 109/l Dose Given

> 75 100%

50-74 75% doses of Cyclophosphamide and

Doxorubicin.

100% doses of Vincristine and

Prednisolone


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Additional Modifications

Vincristine: If patient complains ofsignificant constipation or sensory loss infingers and/or toes, discuss possible dosereduction with Consultant before

administration. Doxorubicin: Maximum cumulative dose =

450mg/m2.

Previous neutropenic sepsis, discuss theuse of prophylactic antibiotics and/or G-CSF support with Consultant.


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NHL CHOP - RIndication: Intermediate and high grade, B-cell NHL expressing

CD20.

2

nd

or 3

rd

line therapy for low grade, B cell lymphoma. Non-Hodgkins lymphoma expressing CD20.

Pre/post - treatment Evaluation:

FBC.

LFT, U&E, Creatinine. Consider ECG +/- echocardiogram if clinical

suspicion of cardiac dysfunction.


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DRUG REGIMEN:DAY(S) DRUGS DOSE ROUTE COMMENTS

1 Rituximab 375mg/m IV

1 Cyclophosphamide 750mg/m IV Bolus via fast

running drip

of 0.9% saline

1 Doxorubicin 50mg/m IV Bolus via fast

running drip

of 0.9% saline


(max 2mg)


bolus injection as per

national protocol

1 - 5 Prednisolone 100mg PO Take in the mornings;

swallow whole with

food


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CONTI

Cycle Frequency: Every 21 days.

Treat to CR or maximum response plus further two

cycles (maximum 8 cycles).

Additional Modifications: Vincristine:

If patient complains of significant constipation or sensory loss in

fingers and/or toes, discuss possible dose reduction with Consultant

before administration. Doxorubicin:Maximum cumulative dose = 450mg/m2


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CONTI

Previous neutropenic sepsis, discuss the use of

prophylactic antibiotics and/or G-CSF support with

Consultant

Rituximab

Circulating tumour cells > 50 x 109/l consider

delay of Rituximab.

Tumour bulk; single lesion >10cm consider delay of

Rituximab

NHL Single Agent


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NHL Single Agent

Rituximab

Indication: Chemotherapy-resistant follicular lymphoma in

last line therapy

Second or third line therapy for other indolent B

cell non-Hodgkins lymphoma expressing CD20

Palliative therapy of aggressive B cell non-

Hodgkins lymphoma expressing CD20


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DRUG REGIMEN:


1, 8 , 15

& 22

Rituximab 375mg/m2 IV Initiate at 100mg/h; if

tolerated increase rate by

100mg/h increments

every 30 minutes to a

maximum of 400mg/hr

Cycle Frequency Once weekly intravenous infusion for

4 weeks


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M.MYELOMA CVAD/VAD

Indication:Newly diagnosed multiple myeloma.

Cycle Frequency:

3 weeklyMinimum of 4 cycles, maximum 6 cycles

depending on response and timing of harvest. At

this time the continuous Thalidomide is stopped.


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DRUG REGIMEN:DAY(S) DRUGS DOSE ROUTE COMMENTS

1 - 4 Doxorubicin 9mg/m2/day

(i.e. total

36mg/m2)

IV Continuous IV

infusion over 4

days in 0.9%

NaCl (mixed with

Vincristine)

1 - 4 Vincristine 0.4mg/day

(i.e. total

1.6mg)

IV Continuous IV

infusion over 4

days in 0.9%

NaCl (mixed with

Doxorubicin)1, 8 + 15 Cyclophosphamide 500mg PO

1-4 + 12-15 Dexamethasone 40mg PO Take in morning;

with food

Miscellaneous regimens:


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Miscellaneous regimens:DISEASE REGIMEN ABBREVIATION

ALL (newly Dx) EARLY INTER Vincritine

Daunorubicin

Cytarabin

Etoposide

ALL HYPER CVAD (cycle I A) Cyclophosphamide

Vincristine

Doxorubicine

Dexamathasone

(cycle B) Methotrexate

Cytarabin

HD ABVD (STAT) Doxorubicin

Bleomycin

Vinblastine

Dacarbazine

CLL / SLL R + B Rituximab

Bendamustine


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Case study:

A 41year old man presents to your clinic for initiatechemotherapy to treat hisALL You explain to the

man and his mother that you will be using several

different chemotherapy agents to treat his disease.

One of the agentsyou will be recom. Acts byblocking DNA n RNA synthesis, however this drug

also causes the production of oxygen radicals,

which can damage cardiac tissue when given at

high doses. In order to avoid this rather serious

side effect, you will carefully monitor levels of the

drug so as to avoid cardiac toxicity if possible.


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AnthracyclinesSimilar drugs Doxorubicin, Daunorubicin, and Idarubicin

MOA Disrupt cellular function by: 1) Block DNA/RNA synthesis.

2) Caue production of O2 radicals, lead to memebrane

damage. 3) Disrupt fluid and ion transport.

Clinical uses Doxo: Solid tumors (breast, ovary, bladder, endometrium,

stomach, lung)

Dauno:Acute leukemia ( AML, ALL, CLL) and neuroblastoma.

Idarubicin:Acute myeloid leukemia.

Side effects Bone marrow suppression, alopecia, cardiac toxicity (we use

dexrazoxane, a compound that acts to decrease free radical

formation)


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