Adverse effects are a significant issue in the treatment of both cytotoxic drugs and newer targeted therapies, leading to dose reductions, dose delays, and treatment discontinuation. Toxicity can reduce quality of life, jeopardies treatment adherence, and necessitate dose reductions and dose delays, all of which can have a negative impact on treatment response and outcome.

1. Adverse Effects of Anti - Cancer Drug
Dr.AWAIS IRSHAD

2. Learning Objectives:
After completing the lecture, students will be able to:
• Describe, and compare the adverse effects of cancer-
treatment drugs

3. Adverse effects are a significant issue in the treatment of both
cytotoxic drugs and newer targeted therapies, leading to dose
reductions, dose delays, and treatment discontinuation.
Toxicity can reduce quality of life, jeopardies treatment adherence,
and necessitate dose reductions and dose delays, all of which can
have a negative impact on treatment response and outcome.

4. • Cancer is a cell disease characterized by uncontrolled
tissue proliferation that is progressive, persistent, and
purposeless.
• Both normal and cancerous cells must go through the cell
cycle phases.

5. ALKYLATING AGENTS:
Adverse Effects:
• Dose-related (Nausea and vomiting)
• Occur primarily in:-
• Bone Marrow (Myelosuppression)
• GIT (Diarrhea)
• Reproductive system.
• Potent vesicants (blistering)
• Tissues damage at the site of administration
• Produce systemic toxicity.

6. • Carcinogenic in nature  increased risk of
secondary malignancies (Acute Myelogenous
Leukemia).

7. Alkylating Agents Acute Toxicity Delayed Toxicity
Mechlorethamine
Nausea and vomiting
• Severe bone marrow depression
• Alopecia and hemorrhagic cystitis (Cyclophosphamide).
• Skin pigmentation, pulmonary fibrosis, and adrenal insufficiency
(Busulfan)
Chlorambucil
Cyclophosphamide
Carmustine • Myelosuppression
• Rarely interstitial lung disease and interstitial nephritis
Lomustine
Altretamine • Myelosuppression, Peripheral neuropathy, Flu-like syndrome
Temozolomide Nausea and vomiting, headache
and fatigue
Myelosuppression, mild elevation in liver function tests, photosensitivity
Procarbazine CNS Depression Myelosuppression, hypersensitivity Reactions
Dacarbazine
Nausea and vomiting
Myelosuppression, CNS toxicity with neuropathy, Ataxia, Lethargy, &
Confusion
Cisplatin Nephrotoxicity, peripheral sensory neuropathy, ototoxicity,
nerve dysfunction
Carboplatin Myelosuppression; Rarely peripheral neuropathy, Renal toxicity, Hepatic
Dysfunction
Oxaliplatin
Nausea and vomiting,
Laryngopharyngeal Dysesthesias
Myelosuppression, peripheral sensory neuropathy, diarrhea
Toxicities (Alkylating Agents & Platinum Analogs)

8. NONCLASSIC ALKYLATINGAGENTS:
Procarbazine:
• Increased risk of secondary cancers (Acute Leukemia)
• Its carcinogenic potential is higher than alkylatingagents.
Dacarbazine:
• Dose-limiting toxicity (Myelosuppression)
• Severe nausea and vomiting
• A potent vesicant
Bendamustine:
• Dose-limiting toxicities (myelosuppression)
• Mild nausea & vomiting
• Hypersensitivity infusion reactions
• Skin rash

9. ANTI-METABOLITES:
ANTIFOLATES:
• Methotrexate
• Pemetrexed
• Pralatrexate
FLUOROPYRIMIDINES:
• 5-Fluorouracil
• Capecitabine
• TAS-102
DEOXYCYTIDINEANALOGS:
• Cytarabine
• Gemcitabine

10. Toxicities (Antimetabolites)
Drug Toxicity
Capecitabine Diarrhea, Hand-foot Syndrome, Myelosuppression, Nausea & Vomiting
5-Fluorouracil Nausea, Mucositis, Diarrhea, Bone Marrow Depression, Neurotoxicity
Methotrexate Mucositis, Diarrhea, Myelosuppression with Neutropenia & Thrombocytopenia
Pemetrexed Myelosuppression, Skin Rash, Mucositis, Diarrhea, Fatigue, Hand-foot Syndrome
Cytarabine Nausea and Vomiting, Myelosuppression with Neutropenia & Thrombocytopenia, CerebellarAtaxia
Gemcitabine Nausea, Vomiting, Diarrhea, Myelosuppression
Fludarabine Myelosuppression, Immunosuppression, Nausea & Vomiting, Fever, Myalgias, Arthralgias
Cladribine Myelosuppression, Nausea & Vomiting, Immunosuppression
6-Mercaptopurine Myelosuppression, Immunosuppression, Hepatotoxicity
6-Thioguanine Myelosuppression, Immunosuppression, & Hepatotoxicity

11. PURINE ANTAGONISTS
• 6-Thiopurines
• Fludarabine
• Cladribine
NATURAL PRODUCT CANCER CHEMOTHERAPYDRUGS
VINCAALKALOIDS:
• Vinblastine
• Vincristine
• Vinorelbine

12. Natural product cancer chemotherapy drugs: Toxicities
Drug Acute Toxicity Delayed Toxicity
Bleomycin Allergic Reactions, Fever, Hypotension Skin Toxicity, Pulmonary Fibrosis, Mucositis,Alopecia
Daunorubicin Nausea & Vomiting, Fever, Red Urine (not hematuria) Cardiotoxicity, Alopecia,Myelosuppression
Docetaxel Hypersensitivity Neurotoxicity, Fluid retention, myelosuppression
with neutropenia
Doxorubicin Nausea, Red Urine (not hematuria) Cardiotoxicity, Alopecia, Myelosuppression,Stomatitis
Etoposide Nausea, Vomiting, Hypotension Alopecia, Myelosuppression
Idarubicin Nausea & vomiting Myelosuppression, Mucositis, Cardiotoxicity
Irinotecan Diarrhea, Nausea, Vomiting Diarrhea, Myelosuppression, Nausea & Vomiting
Mitomycin Nausea & Vomiting Myelosuppression, Mucositis, Anorexia & Fatigue,Hemolytic-
uremic Syndrome
Paclitaxel Nausea, Vomiting, Hypotension, Arrhythmias,
Hypersensitivity
Myelosuppression, Peripheral Sensory Neuropathy
Topotecan Nausea & Vomiting Myelosuppression
Vinblastine Nausea & Vomiting Myelosuppression, Mucositis, Alopecia, Syndrome of
Inappropriate Secretion of Antidiuretic Hormone (SIADH),
Vascular Events
Vincristine None Neurotoxicity with peripheral neuropathy, Paralytic Ileus,
Myelosuppression, Alopecia,SIADH
Vinorelbine Nausea & Vomiting Myelosuppression, Constipation, SIADH

13. TAXANES & OTHER ANTI-MICROTUBULE DRUGS:
• Paclitaxel
• Abraxane (An albumin-bound paclitaxel nanoparticle formulation)
• Docetaxel
• Cabazitaxel
• Ixabepilone
• Eribulin
EPIPODOPHYLLOTOXINS:
• Etoposide
CAMPTOTHECINS:
• Topotecan
• Irinotecan
• Liposomal irinotecan

14. ANTITUMOR ANTIBIOTICS
ANTHRACYCLINES
• Doxorubicin
• Daunorubicin
• Idarubicin
• Epirubicin
• Mitoxantrone (Dihydroxyanthracenedione)
• Dexrazoxane
MITOMYCIN
BLEOMYCIN

15. MISCELLANEOUS ANTI-CANCER DRUGS:
IMATINIB & OTHER TYROSINE KINASE INHIBITORS (TKIs):
• Imatinib
• Dasatinib
• Nilotinib
• Bosutinib
• Ponatinib

16. Toxicities (Miscellaneous anti-cancer drugs)
Drug Acute Toxicity Delayed Toxicity
Bortezomib Nausea & Vomiting,
Fever
Peripheral sensory neuropathy, diarrhea, orthostatic hypotension, fever, pulmonary toxicity,
reversible posterior leukoencephalopathy (RPLS), congestive heart failure (CHF), rare cases
of QT prolongation
Carfilzomib Fever Fatigue, Cardiac Toxicity with CHF and MI, Myelosuppression, Pulmonary Toxicity,
Hepatotoxicity, Orthostatic Hypotension
Erlotinib Diarrhea Skin Rash, Diarrhea, Anorexia, Interstitial Lung Disease
Imatinib Nausea and vomiting Nausea & vomiting, Fluid retention with ankle and periorbital edema, Diarrhea, Myalgias,
CHF
Bosutinib Nausea and vomiting Diarrhea, Fluid Retention, Myelosuppression, Skin Rash Hepatotoxicity
Cetuximab Infusion reaction Skin Rash, Hypomagnesemia, Fatigue, Interstitial Lung Disease
Panitumumab Infusion Reaction
(rarely)
Skin Rash, Hypomagnesemia, Fatigue, Interstitial Lung Disease
Bevacizumab Hypertension,
Infusion Reaction
Arterial Thromboembolic Events, Gastrointestinal Perforations, Wound Healing
Complications, Bleeding Complications, Proteinuria
Ziv-aflibercept Hypertension Arterial Thromboembolic Events, Gastrointestinal Perforations, Wound Healing
Complications, Bleeding Complications, Diarrhea, Mucositis, Proteinuria
Sorafenib Nausea, hypertension Skin Rash, Fatigue And Asthenia, Bleeding Complications, Hypophosphatemia
Sunitinib,
Pazopanib
Hypertension Skin Rash, Fatigue And Asthenia, Bleeding Complications, Cardiac Toxicity

17. GROWTH FACTOR RECEPTOR INHIBITORS:-
• Cetuximab
• Panitumumab
• Necitumumab
• Erlotinib:
• Afatinib
• Osimertini
b
• Bevacizumab
• Ziv-Aflibercept
• Ramucirumab
• Sorafenib
• Sunitinib
• Pazopanib

18. Drugs causing Bone Marrow Depression, Aplastic Anemia &Thrombocytopenia
Drugs causing bone
marrow
depression
Drugs causing aplastic
anemia
Drugs causing
Thrombocytopenia
Carboplatin Cisplatin Dacarbazine
Vinblastine Docetaxel Carboplatin
Doxorubicin Altretamine 5-flurouracil
Melphalan Topotecan Lomustine
Paclitaxel Paclitaxel Mitomycin
Cyclophosphamide Cytarabine Thiotepa

19. Drugs causing diarrhea and mucositis
Drugs causing diarrhea. Drugs causing mucositis
Methotrexate Bleomycin
Paclitaxel Actinomycin D
Cytarabine Daunorubicin
Nitrosourea Doxorubicin
Irinotecan Fluorouracil
Floxuridine Methotrexate

20. Emetogenic potential of cytotoxic drugs:
Mild Moderate High
Chlorambucil Cytarabine Mustine
Bleomycin Carboplatin Cisplatin
Busulfan Procarbazine Cyclophosphamide
Fluorouracil` Vinblastine Actinomycin D
6-Thioguanine Doxorubicin Dacarbazine
Hydroxyurea Daunorubicin Lomustine

21. Drugs causing stomatitis:
Drugs causing stomatitis
Methotrexate
Irinotecan
Cytarabine
5- Fluorouracil
Vincristine, Vinblastine
Etoposide

22. Drugs causing hair follicle toxicity:
Drugs causing hair follicle toxicity
Doxorubicin
Methotrexate
Ifosfamide
Cyclophosphamide
Daunorubicin
Vincristine
Paclitaxel
Etoposide

23. Drugs causing renal toxicity:
Drugs causing renal toxicity
Cisplatin
Ifosfamide
Mitomycin
Plicamycin
Streptozotocin

24. Drugs causing pulmonary toxicities:
Drugs
causing
Acute
pneumoniti
s
Drugs
causing
Pulmonary
fibrosis
Drugs
causing
Hypersensitiv
ity
pneumonitis
Drugs
causing Non
cardiogenic
pulmonary
Edema
Bleomycin
Bleomycin
Procarbazine Cyclophosphamide
Vinca alkaloids Azathioprine Methotrexate
Methotrexate Bleomycin Cytarabine
Procarbazine Methotrexate Mitomycin
Mitomycin - -

25. Drugs causing cardiac toxicities:
Drugs causing
Left ventricular
Dysfunction
Drugs
causing
Cardiac
Ischemia
Drugs causing
QT
Prolongation
Doxorubicin Capecitabine
Paclitaxel
Epirubicin Fluorouracil
Paclitaxel

26. Drugs causing CNS toxicities:
Drugs causing
Encephalopathy
Drugs
causing
Seizures
Drugs causing
Aseptic
Meningitis
Drugs causing
Cerebral
Infarctions
Methotrexate Methotrexate Methotrexate Methotrexate
Cis-platinum Etoposide
Cytosinarabinoside
Cyclosporine
5-fluorouracil Vincristine Platinum
Derivatives
Procarbazine Dacarbazine
Etoposide Cyclosporine

27. Drugs causing ocular toxicities:
Drugs
causing
Blurred
vision
Drugs
causing
Photophob
ia
Drugs
causin
g
Catara
ct
Drugs
causing
Conjunctivi
tis
Drugs
causin
g
Keratiti
s
Drugs
causing
Optic
Neuropathy
Cisplatin 5-Florouracil Tamoxifen Oxaliplatin 5-Florouracil Cisplatin
Cyclophosphamid
e
Methotrexate Anastrazole Cyclophosphamide Capecitabine Carboplatin
Methotrexate Fludarabine Busulfan Methotrexate Tamoxifen Methotrexate
Imatinib Cytosine 5-Florouracil Cetuximab Paclitaxel
Tamoxifen Arabinoside Docetaxel Erlotinib Vincristine
Mitomycin-C Pentostatin Chlorambucil Tamoxifen

28. Drugs causing skin toxicities:
Drugs
causing
nail
changes
Drugs
causing
hyperpigmentati
on
Drugs
causing
Hypersensitiv
ity
Bleomycin Bleomycin Carboplatin
Cyclophosphamide Cyclophosphamide Doxorubicin
Doxorubicin Busulfan Cyclophosphamide
5-Flurouracil Carmustine Cytarabine
Paclitaxel Dactinomycin L- asparginase
Hydroxyurea Methotrexate Docetaxel

29. Drugs causing hepatotoxicity:
Drugs causing hepatotoxicity
Cyclophosphamide
5-Flurouracil
Methotrexate
6-Mercaptopurine
Doxorubicin

30. Anticancer drugs causing extravasations:
Vesicants Irritants
Doxorubicin Etoposide
Mechlorethamine Carmustine
Mitomycin Dacarbazine
Vinblastine Paclitaxel

31. Serious adverse effects of anticancer drugs