The era of modern chemotherapy began in the early 1940s when Goodman and Gilman first administered nitrogen mustard to lymphoma patients. Although nitrogen mustard was originally developed as a chemical weapon, its toxic effects on the lymphatic system led to clinical trials of its use in cancer treatment. This marked the beginning of chemotherapy as an active field of cancer research and therapy development.

2.  Era of modern chemotherapy began in early 1940s
 Goodman and Gilman first administered nitrogen
mustard to patients with lymphoma
◦ nitrogen mustard was developed as a war gas during (world
war I) rather than as a medicine
◦ toxic effects on the lymphatic system led to clinical trials

3.  G1 phase: cell prepares for DNA
synthesis
 S phase: cell generates complete
copy of genetic material
 G2 phase: cell prepares for
mitosis
 M phase: replicated DNA is
condensed and segregated
into chromosomes
 G0 phase: resting state

4.  Cell cycle phase –
specific
◦ agents with major
activity in a particular
phase of cell cycle
◦ schedule dependent
 Cell cycle phase –
nonspecific
◦ agents with significant
activity in multiple
phases
◦ dose dependent

5.  Alkylating agents
◦ nitrogen mustards
◦ thiotepa, busulfan
◦ nitrosoureas, mitomycin
◦ procarbazine, dacarbazine
 Taxanes
◦ paclitaxel, docetaxel
◦ nab-paclitaxel
 Topoisomerase II inhibitors
◦ etoposide
 Platinum Complexes
◦ cisplatin, carboplatin
◦ oxaliplatin
Anthracyclines
doxorubicin, daunorubicin
idarubicin, mitoxantrone
Antimetabolites
methotrexate
purine antagonists
pyrimidine antagonists
Tubulin interactive agents
vincristine, vinblastine
Miscellaneous agents
bleomycin
asparaginase
Hydroxyurea
Targeted agents
Hormonal agents
Monoclonal antibodies

6.  Most chemotherapy drugs are active in cells that are rapidly
multiplying so besides their cytotoxic effects on cancerous
cells they are also toxic to normal cells that are actively
multiplying.
 Thus common toxicity of chemo agents are –
◦ Neutropenia, anemia, and thrombocytopenia
(myelosuppression or bone marrow suppression)
◦ Mucositis, diarrhea (GI toxicity)
◦ Nausea and vomiting
◦ Alopecia
◦ Sterility/Infertility (especially sterility in males)

7.  Side effects are dependent upon:
◦ Type of drug
◦ Dose that was given
◦ Frequency of administration
◦ Number of drugs in any particular regime
◦ Route of administration – drug concentration
◦ Patient’s co-morbidity
◦ Age ?

8. Activities of Daily Living (ADL)
*Instrumental ADL refer to
preparing meals,
shopping for groceries or
clothes, using the
telephone, managing money,
etc.
**Self care ADL refer to bathing,
dressing and
undressing, feeding self, using
the toilet, taking
medications, and not bedridden.

9.  Mature circulating
haematopoeitic cells die
off according to their
respective life spans
 Deficient replacements
from the marrow
 Clinical manifestations
including leucopenia,
thrombocytopenia,
anemia
 Complications arise in
severe cases

10.  Neutropenia is defined
as an absolute
neutrophil count (ANC)
of <500 cells/mm3 or an
ANC that is expected to
decrease to <500
cells/mm3 during the
next 48 hours.
 In neutropenic patients,
fever (single oral
temperature ≥38.3°C or
sustained temp. ≥38°C
for 1 hour) should be
considered evidence of
infection and treated
accordingly.
MASCC Score
Treatment :-
G-CSF or GM-CSF support along with
Antibiotics and antifungal.

11.  Defined as a platelet count <1003/μl (CTCAE)
 Complication- hemorrhage
 The risk of spontaneous bleeding including
intracranial hemorrhage is increased when the
platelet count drops to <103/μl.
 If the platelet count is <1003/μl at the
beginning of a new cycle, the chemotherapy is
delayed and the successive dose of treatment is
decreased.
 Drugs that affect the early hematopoietic
progenitors, such as the nitrosureas, mitomycin
C, busulfan, and melphalan delayed and
cumulative thrombocytopenia
 New biologic agents- lenalidomide

12.  Causes-
◦ Antiangiogenic therapy (bevacizumab, sunitinib, sorafenib)
◦ Immunomodulatory agents (thalidomide- or lenalidomide-based
combination regimens)
◦ Hormonal therapy agents (e.g., tamoxifen)
◦ Erythropoiesis-stimulating agents
◦ Central venous access devices
◦ Transfusions
 Patients with cancer have a 3-fold higher risk of
recurrent VTE and 2-fold higher risk of anticoagulant-
related bleeding compared with patients without cancer.
 CLOT trial- LMWH is the preferred treatment for initial
and long-term treatment compared with UFH and
vitamin K antagonists (VKA).

13.  Acute CINV- within 24hrs after chemotherapy
 Delayed CINV- more than 24hrs after chemo
eg.- cisplatin, carboplatin , anthracyclines
cyclophosphamide
 Anticipatory Nausea and vomiting- occur as
the result of a conditioned response to prior
episodes of CINV

16.  Commonly with Adriamycin, epirubicin
 All hair follicles
 Educate and reassure that hair will growback (about 3 – 5
month post chemo )

17.  Commonly seen with
5-FU, Adriamycin,
Cisplatin
 Ulcer Burning
Sensation Pain
 Good oral hygiene
 Cryotherapy (ice chips)
 Good diet control
 Analgesics
 Antibiotics &
Antifungals as
required

18.  Commonly with- 5-FU, capecitabine, and
irinotecan (acute cholinergic properties)
 Targeted thearpy- bortezomib, erlotinib, gefitinib,
sorafanib, sunitinib, imatininib, temsirolimus,
everolimus.
 Dose-related adverse effect
 Multifactorial process whereby acute damage to
the intestinal mucosa (loss of intestinal
epithelium, superficial necrosis & inflammation)
causes an imbalance between absorption and
secretion in the small bowel.
 Neutropenic enterocolitis- myeloablative therapies

19. Dietary Management –
fiber-rich foods such as bran,
fruits,vegetables and nuts
Prune juice is commonly used to
relieve constipation
Increase fluid intake
Increase physical activities
Laxatives
Bulk Laxatives
Osmotic Laxatives
Polyethylene Glycol
Lactulose
Magnesium and Sulfate Salts
Stimulant Laxatives
Anthranoid Laxatives- senna
Polyphenolic(Diphenylmethane)
Detergents/Stool Softeners
Liquid Paraffin
Opioid Antagonists for Opioid
induced Constipation-
Methylnaltrexone is a quaternary
derivative of naltrexone
Enemas and Suppositories
Managing Fecal Impaction- digital
evacuation

20. Other drugs causing pulmonary toxicity-
•Antimetabolites- Methotrexate, gemcitabine, fludrabine
•Taxane- Docetaxel, paclitaxel
•TKI- EGFR inhibitors (gefitinib, erlotinib),
Kit/BCR-ABL inhibitors (imatinib, dasatinib)
•Myeloma drugs- bortezomib, thalidomide, lenalidomide
•mTOR inhibitor- sirolimus, everolimus, temsirolimus
•Monoclonal Ab’s- VEGF inhibitor (Bevacizumab)
EGFR inhibitor (trastuzumab)
•Immunotherapy- Nivolumab, Iplimumab

21.  Anthracyclines- Reversible acute cardiotoxicity and delayed irreversible dilated
cardiomyopathy
 Trastuzumab- cardiomyopathy
 5-Fluorouracil (5-FU)- angina, atrial/ ventricular arrhythmias, MI &
cardiogenic shock
 Cyclophosphamide- acute myopericarditis associated with high-dose therapy
and more commonly, acute or subacute CHF (reversible)
 Ifosfamide- Nonischemic cardiomyopathy (NICM)
 Paclitaxel- multiple: asymptomatic bradycardia & life threatening atrial and/or
ventricular rhythm disturbances and/or conduction abnormalities
 Bevacizumab- A recent US FDA black box warning was placed on bevacizumab
after an increase in risk of MI, angina, and heart disease
 Rituximab- no long-term cardiac toxicity; however, arrhythmias with cardiac
death have been reported

23.  Taxanes, Platinum group
 Tingling, burning, weakness or numbness
 Shaking or trembling
 Difficulty in picking up objects, writing,
buttoning clothes
 Advice to patients
◦ Be careful with sharp objects
◦ Avoid exposure to cold
◦ Wear shoes / sandals with rubber soles

26.  VESICANTS- Are drugs that can cause tissue
necrosis, pain and tissue sloughing at the site of
extravasation.
 IRRITANTS- Are drugs that can cause aching,
tightness, phlebitis with or without inflamation

28.  Leukemias secondary to chemotherapy agents have
poor prognosis.
 Secondary to alkylating agents:-
◦ Most often occur after 5 – 7 years
◦ Often have MDS preceding leukemia
◦ Frequently FAB class M1 or M2
◦ Alterations of chromosomes 5 and/or 7 in 60% – 90% cases
 Secondary to topo II inhibitors:-
◦ Diagnosed 2 -3 yrs after tx
◦ Most often FAB class M4 or M5
◦ Frequent translocation of chromosome 11 (11q23)
t(11;19)(q23;p13)

29.  Neurologic
◦ CNS: cytarabine, methotrexate, ifosfamide
◦ Peripheral: paclitaxel, oxaliplatin, vincristine
 Gastrointestinal
◦ Nausea and vomiting: cisplatin, doxorubicin, cyclophosphamide
◦ Mucositis: methotrexate, melphalan, etoposide, 5-FU
 Pulmonary- Methotrexate, bleomycin
 Cardiovascular- Anthracyclines, trastuzumab, 5 FU, cyclophosph
 Hepatic- busulfan
 Metabolic- Ifosfamide, cisplatin
 Renal
◦ Hemorrhagic cystitis: cyclophosphamide, ifosfamide
◦ Renal failure: cisplatin

30.  Dermatologic
◦ Hand-foot syndrome: 5-FU, capecitabine, cytarabine
 Immune System
◦ Immunosuppression: fludarabine, cyclophosphamide, steroids
◦ Hypersensitivity: paclitaxel, asparaginase, bleomycin
 Miscellaneous Toxicity
◦ Asparaginase
 Coagulation disorders
 Hyperlipidemia
 Hyperglycemia
 Pancreatitis
◦ Etoposide- Hypotension, flushing (infusion-related)
◦ Irinotecan- Acute and delayed diarrhea (SN-38 metabolite)