BY R ph.

HUMAIRA SHAFIQ IV Pharmacist at NIBD

CONTENTS:
History Hematological Malignancy Chemo Regimens Miscellaneous regimens Case history

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.

Hematological Malignancies

TYPES

LEUKAEMIAS

LYMPHOMAS

MYELOMA S

ALL

AML

CLL

CML

HODGKIN LYMPHOMAS

NON-HODGKIN LYMPHOMAS

ACUTE LYMPHOBLASTIC LEUKEMIA: (ALL)

a)
b) c) d) e)

Cancer Of The White Blood Cells Characterized By Excess Lymphoblasts. 25 Years Of Age & Peak Old Age. Variant Features Of All ALL With Cytoplasmic Granules Aplastic Presentation Of ALL ALL With Eosinophilia Relapse Of ALL Secondary ALL

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.

DIFFERENCE BETWEEN ALL & CLL

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.

ACUTE LYMPHOBLASTIC CHRONIC LYMPHOBLASTIC LEUKEMIA LEUKEMIA

ACUTE MYELOID LEUKEMIA (AML)

Cancer Of 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

CHRONIC MYELOID LEUKEMIA

Leukemia cells tend to build up in the body 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 bone marrow

DIFFERENCE BETWEEN AML/CML:

Granulocytic, myelocytic, myeloblastic, or myeloid. 20% childhood leukemias Over a short period of days to weeks Children with certain genetic syndromes Fanconi anemia, Bloom syndrome, Kostmann syndrome, and Down syndrome.

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 these two chromosomes.

ACUTE MYELOID LEUKEMIA

CHRONIC MYELOID LEUKEMIA

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 Of Hodgkin's Disease 30 Subtypes Of Non-hodgkin's Lymphoma.

TYPES OF HD
Nodular sclerosis HD. Mixed cellularity HD. Lymphocyte-rich HD. Lymphocyte-depleted HD. Nodular lymphocyte predominant HD.

TYPES OF NHL
a) b)

c)
d) e) f) g)

Aggressive (Fast-growing) Indolent (Slow-growing) B-cell Non-hodgkin Lymphomas Burkitt Lymphoma CLL/SLL Diffuse Large B-cell Lymphoma Follicular Lymphoma Immunoblastic Large Cell Lymphoma Precursor B-lymphoblastic Lymphoma Mantle Cell Lymphoma.

a) b) c)

T-cell Non-hodgkin Lymphomas Mycosis Fungoides Anaplastic Large Cell Lymphoma Precursor T-lymphoblastic Lymphoma

DIFFERENCE B/W HN & NHN

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.

HODGKIN DISEASE

NON-HODGKIN LYMPHOMA

SYMP. OF HN &

NHL

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.

TYPES OF MYELOMA:

Asymptomatic Smoldering Or Indolent Myeloma Increased Level Of Plasma Cells Elevated M-protein No Anemia Monoclonal Gammopathy Of Undetermined Significance (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.

SYMPTOMS:

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

DRUG REGIMEN:
DAY(S) DRUGS DOSE ROUTE COMMENTS

1 - 10

Cytarabine

100mg/m2 IV BD

IV Bolus

1,3+5

Daunorubicin

50mg/m2 OD

IV

IV Infusion in100ml 0.9% NaCl over 1hr

1-5

Etoposide

100mg/m2 IV OD

IV Infusion in 500mls 1L 0.9% NaCl over 1hr

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%.

Dose Modifications: (Renal)

Serum creatinine 105 265mol/l reduce daunorubicin dose by 25%. Serum creatinine > 265mol/l reduce daunorubicin dose by 50%. CrCl 45-60 ml/min give 85% dose of etoposide. 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

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

Concurrent Medication:
Consider Allopurinol 300mg od PO (100mg if creatinine clearance <20mls/min) for first week. Give appropriate mouthcare, and appropriate systemic antifungal, PCP and antiviral prophylaxis as per local policy. Anti-emetics refer to local policy

AML

High Dose Cytarabine

Indication:
Consolidation chemotherapy as part of the treatment of acute myeloid leukaemia (AML)

DAY(S) 1, 3 + 5

DRUGS Cytarabine

DOSE

ROUTE COMMENTS IV Infusion in 250mls 0.9% NaCl over 4hrs

1.5g/m2 BD/ IV 3g/m2 BD

Cycle Frequency

Two courses of chemotherapy.

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 to 100 x 109/l.

Concurrent Medication:

Consider Allopurinol 300mg od PO (100mg if creatinine clearance <20mls/min) for first week. Prednisolone eye drops (Predsol 0.5%) should be given during each course of cytarabine. Give appropriate mouthcare, and appropriate systemic antifungal, PCP and antiviral prophylaxis as per local policy. Anti-emetics refer to local policy.

CML
Indication:

CVP

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

Drug Regimen:
DAY(S) DRUGS DOSE ROUTE COMMENTS

Cyclophosphamide

750mg/m

IV

Bolus via fast running drip of 0.9% saline.

Vincristine

1.4mg/m (max 2mg)

IV

In 20mls 0.9% saline bolus injection as per national protocol Take in the mornings; swallow whole with food

1-5

Prednisolone

40mg/m

PO

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.

Dose Modifications:
Renal: Creatinine clearance >50 10-50

<10

Modification 100% 75% dose of Cyclophosphamide 50% dose of Cyclophosphamide

CONTI..
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.

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

Concurrent Medication: Consider Allopurinol 300mg OD PO (100mg if creatinine clearance <20mls/min) for first 2 cycles. H2-antagonist or PPI if significant indigestion with steroids. Anti-emetics refer to local policy.

CLL

CVP-R

Indication: Follicular and other indolent lymphomas.

Waldenstroms macroglobulinaemia. Chronic Lymphocytic Leukaemia. Aggressive lymphoma where more intensive chemotherapy is not indicated. Cycle Frequency: Repeat every 21-28 days to a maximum clinical response Usually 6-8 cycles

DRUG REGIMEN:
DAY(S) DRUGS DOSE ROUTE COMMENTS

Rituximab

375mg/m

IV

Cyclophosphamide

750mg/m

IV

Bolus via fast running drip of 0.9% saline.

In 20mls 0.9% saline bolus injection Take in the mornings; swallow whole with food.

Vincristine

1.4mg/m (max 2mg) 40mg/m

IV

1-5

Prednisolone

PO

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; if tolerated 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.

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. 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.

Concurrent Medication:
Consider Allopurinol 300mg od PO (100mg if creatinine clearance <20mls/min) for first 2 cycles. H2-antagonist or PPI if significant indigestion with steroids. Premedicate Rituximab using Paracetamol 1gm PO and Chlorpheniramine 10mg IV; consider corticosteroids e.g. 100mg Hydrocortisone Anti-emetics refer to local policy

NHL:

FC-R

INDICATION:
Mantle Cell Lymphoma

Pre/post-treatment Evaluation : FBC, LFT, U&E, Creatinine

Drug Regimen:
DAY(S) DRUG DOSE ROUTE COMMENTS

Rituximab

375mg/m2

IV

1-3

Cyclophosphamide 250mg/m2

IV

Bolus injection via fast running drip of 0.9% NaCl IV infusion in 100ml 0.9% NaCl over 30min

1-3

Fludarabine

25mg/m2

IV

Alternatively an ORAL schedule:

DAY(S) 1-5 1-5 DRUG Cyclophosphamide Fludarabine DOSE 150mg/m2 24mg/m2 ROUTE COMMENTS PO PO With breakfast With lunch

Cycle Frequency

Repeat every 28 days Maximum of 6 cycles

Concurrent Medication

Allopurinol 300mg od PO (100mg if creatinine clearance <20mls/min) for first 2 cycles. Oral systemic PCP prophylaxis should be given according to local protocol and for 12 weeks after completion of chemotherapy. Anti-emetics as per local policy

Dose Modifications:
Renal: Reduce to 50% dose if renal impairment (CrCl between 30-60ml/min) Do not give if creatinine clearance < 30ml/min

Haematological:
If neutrophils <1 x 109/l or platelets <75 x 109/l, delay treatment for 1 week If neutrophils <1 x 109/l or platelets <75 x 109/l, after a delay of 2 weeks then treatment should go ahead at 50% of the dose. If neutrophils are below 0.5 x 109/l or platelets below 50 x 109/l by the time the next course is due, delay treatment until counts rise to at least these levels, with dose modifications as above if necessary.

NHL
Indication:

CHOP

Aggressive non-Hodgkins lymphoma Mantle cell lymphoma Second or third line treatment for indolent lymphoproliferative disorders Pre-treatment Evaluation: FBC. LFT, U&E, Creatinine. Consider ECG +/- echocardiogram if clinical suspicion of cardiac dysfunction.

Drug Regimen:
DAY(S) DRUGS DOSE ROUTE COMMENTS

Cyclophosphamide

750mg/m

IV

Bolus via fast running drip of 0.9% saline Bolus via fast running drip of 0.9% saline In 20mls 0.9% saline bolus injection as per national protocol Take in the mornings; swallow whole with food

Doxorubicin

50mg/m 1.4mg/m (max 2mg) 100mg

IV

Vincristine

IV

1-5

Prednisolone

IV

Conti
Additional Information:
Consider Vincristine 1mg for elderly patients (at clinicians discretion).

Cycle Frequency:
Every 21 days. Treat to CR or maximum response plus further two cycles (maximum 8 cycles). Concurrent Medication: Allopurinol 300mg od PO (100mg if creatinine clearance <20mls/min) for first 2 cycles. Anti-emetics - refer to local protocol.

Dose Modifications:

Hepatic;
Serum Bilirubin
<1.5 x upper limit of normal

Modification
100%

1.5-3.0 x upper limit of normal >3.0 x upper limit of normal

50% doses of Doxorubicin 100% dose of other drugs 25% doses of Doxorubicin 100% dose of other drugs

RENAL:
Creatinine clearance (mls/min)
>50

Modification

100%

10-50

75% dose of Cyclophosphamide

<10

50% dose of Cyclophosphamide

Haematology:
Neutrophils x 109/l > 0.1 < 0.1 Platelets x 109/l > 75 50-74 Dose Given 100% Delay all drugs for 1 week Dose Given 100% 75% doses of Cyclophosphamide and Doxorubicin. 100% doses of Vincristine and Prednisolone Delay all drugs for 1 week.

<50

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. Previous neutropenic sepsis, discuss the use of prophylactic antibiotics and/or GCSF support with Consultant.

NHL
Indication:

CHOP - R

Intermediate and high grade, B-cell NHL expressing CD20. 2nd or 3rd 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.

DRUG REGIMEN:
DAY(S) DRUGS DOSE ROUTE COMMENTS 1 Rituximab 375mg/m IV

Cyclophosphamide

750mg/m

IV

Bolus via fast running drip of 0.9% saline

Bolus via fast running drip of 0.9% saline In 20mls 0.9% saline bolus injection as per national protocol Take in the mornings; swallow whole with food

Doxorubicin

50mg/m

IV

Vincristine

1.4mg/m IV (max 2mg) 100mg PO

1-5

Prednisolone

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

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 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 nonHodgkins lymphoma expressing CD20

DRUG REGIMEN:
DAY(S) DRUGS DOSE ROUTE COMMENTS 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

M.MYELOMA

CVAD/VAD

Indication:
Newly diagnosed multiple myeloma. Cycle Frequency: 3 weekly Minimum of 4 cycles, maximum 6 cycles depending on response and timing of harvest. At this time the continuous Thalidomide is stopped.

DRUG REGIMEN:
DAY(S) DRUGS DOSE ROUTE COMMENTS 1-4 Doxorubicin 9mg/m2/day IV (i.e. total 36mg/m2) Continuous IV infusion over 4 days in 0.9% NaCl (mixed with Vincristine) Continuous IV infusion over 4 days in 0.9% NaCl (mixed with Doxorubicin)

1-4

Vincristine

0.4mg/day (i.e. total 1.6mg)

IV

1, 8 + 15

Cyclophosphamide

500mg

PO

1-4 + 12-15

Dexamethasone

40mg

PO

Take in morning; with food

Miscellaneous regimens:
DISEASE ALL (newly Dx) REGIMEN EARLY INTER ABBREVIATION Vincritine Daunorubicin Cytarabin Etoposide

ALL

HYPER CVAD (cycle I A)

Cyclophosphamide Vincristine Doxorubicine Dexamathasone

Methotrexate Cytarabin Doxorubicin Bleomycin Vinblastine Dacarbazine

(cycle B) HD ABVD (STAT)

CLL / SLL

R+B

Rituximab Bendamustine

Case study:

A 41year old man presents to your clinic for initiate chemotherapy to treat his ALL 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 by blocking 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.

Anthracyclines
Similar 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.
Bone marrow suppression, alopecia, cardiac toxicity (we use dexrazoxane, a compound that acts to decrease free radical formation)

Side effects