Chemotherapy: Anticancer Drug Classes, Mechanisms, Regimens, Adverse Effects, and Supportive Care

Introduction

Chemotherapy refers to drugs used to treat cancer by killing or inhibiting the growth of malignant cells. Anticancer pharmacology includes traditional cytotoxic chemotherapy, targeted therapy, immunotherapy, hormonal therapy, and adjunctive agents. Treatment selection depends on cancer type, stage, molecular markers, and patient factors. Modern oncology increasingly uses biomarker-driven therapy and combination approaches.

Cell Cycle and Chemotherapy

Cell Cycle Phases and Drug Specificity

Phase	Description	Duration	Cell Cycle-Specific Drugs	Cell Cycle-Nonspecific Drugs
G0 (Resting)	Quiescent, non-dividing cells	Variable months-years	Not targeted	Alkylating agents, nitrosoureas
G1 (First gap)	Cell growth, protein synthesis	6-12 hours	Erlotinib, lapatinib (EGFR inhibitors)	Platinum compounds
S (Synthesis)	DNA replication	6-8 hours	Antimetabolites (5-FU, methotrexate, gemcitabine, cytarabine), topoisomerase I inhibitors	Mitomycin
G2 (Second gap)	Preparation for mitosis, DNA repair	2-6 hours	Etoposide, bleomycin, irinotecan	Cyclophosphamide
M (Mitosis)	Cell division	0.5-1 hour	Taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine, vinblastine)	Doxorubicin, dactinomycin

Cytotoxic Chemotherapy Classes

Alkylating Agents

Drug Class	Mechanism	Examples	Indications	Key Toxicities
Nitrogen mustards	DNA crosslinking via alkyl groups (N-7 guanine)	Cyclophosphamide, ifosfamide, melphalan, chlorambucil	Lymphoma, breast, ovarian, multiple myeloma, CLL	Hemorrhagic cystitis (cyclophosphamide/ifosfamide - use mesna), myelosuppression, cardiotoxicity (high dose cyclophosphamide), SIADH
Platinum analogs	DNA crosslinking (intrastrand and interstrand)	Cisplatin, carboplatin, oxaliplatin	Lung, ovarian, testicular, colorectal, head/neck	Cisplatin: nephrotoxicity, neurotoxicity, ototoxicity, N/V; Carboplatin: myelosuppression (dose by AUC); Oxaliplatin: cold-induced neuropathy
Nitrosoureas	DNA crosslinking (alkylation + carbamoylation)	Carmustine (BCNU), lomustine (CCNU)	Brain tumors, lymphoma	Delayed/prolonged myelosuppression, pulmonary fibrosis
Triazenes	DNA methylation at O-6 guanine	Temozolomide, dacarbazine	Glioblastoma, melanoma, lymphoma	Myelosuppression

Antimetabolites

Drug	Mechanism	S-Phase Specific	Indications	Key Toxicities
Methotrexate	Dihydrofolate reductase inhibitor (blocks thymidine synthesis)	Yes	ALL, lymphoma, breast, choriocarcinoma, RA	Mucositis, myelosuppression, hepatotoxicity, pneumonitis, nephrotoxicity (high dose)
5-Fluorouracil (5-FU)	Thymidylate synthase inhibitor + RNA incorporation	Yes	Colon, breast, gastric, head/neck, pancreatic	Mucositis, diarrhea, hand-foot syndrome, myelosuppression, cardiotoxicity
Capecitabine	Oral prodrug of 5-FU	Yes	Breast, colon, gastric	Hand-foot syndrome, diarrhea
Cytarabine (Ara-C)	DNA polymerase inhibitor, chain termination	Yes	AML, ALL, NHL	Cerebellar toxicity (high dose), myelosuppression, mucositis
Gemcitabine	Ribonucleotide reductase inhibitor + chain termination	Yes	Pancreatic, lung, breast, bladder, ovarian	Myelosuppression, flu-like syndrome, rash, pulmonary edema
Fludarabine	DNA polymerase inhibitor	Yes	CLL, indolent NHL	Lymphopenia (prolonged), myelosuppression, autoimmune hemolytic anemia
Pemetrexed	Multi-targeted antifolate (thymidylate synthase, DHFR, GARFT)	Yes	Non-squamous NSCLC, mesothelioma	Myelosuppression, fatigue, rash; must supplement with B12 and folate

Topoisomerase Inhibitors

Drug	Target	Mechanism	Indications	Key Toxicities
Doxorubicin (Adriamycin)	Topoisomerase II	Intercalation, topo II poisoning, ROS generation	Breast, lymphoma, sarcoma, AML, ALL	Cardiotoxicity (cumulative, dose-dependent; limit <450-550 mg/m2), myelosuppression, mucositis, alopecia, extravasation injury
Daunorubicin	Topoisomerase II	Same as doxorubicin	AML, ALL	Same as doxorubicin (cardiotoxicity)
Epirubicin	Topoisomerase II	Same as doxorubicin (less cardiotoxic)	Breast, gastric	Similar to doxorubicin (less cardiotoxic)
Idarubicin	Topoisomerase II	Same as doxorubicin (oral available)	AML	Similar
Mitoxantrone	Topoisomerase II	Intercalation, topo II poisoning	AML, prostate, MS	Cardiotoxicity, myelosuppression
Etoposide	Topoisomerase II	Topoisomerase II poisoning (G2-phase)	Small cell lung, testicular, lymphoma	Myelosuppression, secondary AML (with topo II), hypersensitivity
Irinotecan	Topoisomerase I	Topoisomerase I poisoning	Colon, pancreatic	Diarrhea (early and delayed), myelosuppression
Topotecan	Topoisomerase I	Same as irinotecan	Ovarian, small cell lung	Myelosuppression

Microtubule Targeting Agents

Drug	Mechanism	Phase Specificity	Indications	Key Toxicities
Paclitaxel (Taxol)	Promotes microtubule assembly, inhibits depolymerization	M-phase	Breast, ovarian, lung, head/neck, bladder	Neuropathy (sensory), myelosuppression (neutropenia), hypersensitivity (Cremophor), alopecia
Docetaxel (Taxotere)	Same as paclitaxel	M-phase	Breast, prostate, lung, gastric, head/neck	Neuropathy, myelosuppression (neutropenia, febrile neutropenia), fluid retention, nail changes, rash
Nab-paclitaxel (Abraxane)	Albumin-bound paclitaxel	M-phase	Breast, pancreatic, lung	Less hypersensitivity, less neutropenia than paclitaxel
Vincristine	Inhibits microtubule assembly	M-phase	ALL, lymphoma, Wilms tumor, brain tumors	Neuropathy (sensory, motor, autonomic), SIADH, constipation; minimal myelosuppression
Vinblastine	Same as vincristine	M-phase	Hodgkin, testicular, bladder	Myelosuppression > neuropathy
Vinorelbine	Same as vincristine	M-phase	NSCLC, breast	Myelosuppression, neuropathy

Antibiotics (Antitumor)

Drug	Mechanism	Indications	Key Toxicities
Bleomycin	DNA strand breaks (free radicals)	Hodgkin, testicular, head/neck	Pulmonary fibrosis (dose-related >400 U), skin hyperpigmentation, mucositis
Dactinomycin (Actinomycin D)	DNA intercalation, RNA synthesis inhibition	Wilms tumor, Ewing sarcoma, gestational trophoblastic	Myelosuppression, mucositis, extravasation injury
Mitomycin C	DNA crosslinking (bioreductive alkylation)	Gastric, pancreatic, bladder	Myelosuppression (delayed, cumulative), hemolytic uremic syndrome, pulmonary fibrosis

Molecular Targeted Therapy

Tyrosine Kinase Inhibitors (TKIs)

Drug	Target	Cancer Indications	Key Toxicities
Imatinib	BCR-Abl, c-KIT, PDGFR	CML (first-line), GIST	Edema, rash, muscle cramps, myelosuppression; well tolerated
Dasatinib	BCR-Abl (multiple conformations), SRC	CML (second-line, resistance)	Pleural effusion, pulmonary hypertension, QT prolongation
Nilotinib	BCR-Abl	CML (second-line, resistance)	QTc prolongation, pancreatitis, hyperglycemia, cardiovascular events
Erlotinib	EGFR	NSCLC (EGFR mutant), pancreatic	Rash, diarrhea, interstitial lung disease
Osimertinib	EGFR T790M (resistance mutation)	NSCLC (EGFR T790M, first-line)	Rash, diarrhea, nail changes, ILD
Sorafenib	VEGFR, PDGFR, RAF	RCC, HCC	Hand-foot syndrome, diarrhea, hypertension, hypophosphatemia
Sunitinib	VEGFR, PDGFR, c-KIT	RCC, GIST, pancreatic NET	Fatigue, hypertension, hypothyroidism, hand-foot syndrome, myelosuppression
Lapatinib	HER2, EGFR	Breast (HER2+)	Diarrhea, rash, hepatotoxicity

Monoclonal Antibodies

Drug	Target	Mechanism	Indications	Key Toxicities
Rituximab	CD20	ADCC, CDC, apoptosis	NHL, CLL, RA, autoimmune	Infusion reactions, PML (rare), hepatitis B reactivation
Trastuzumab (Herceptin)	HER2	ADCC, HER2 signaling inhibition	Breast (HER2+), gastric (HER2+)	Cardiotoxicity (reversible, particularly with anthracyclines)
Pertuzumab	HER2 (dimerization domain)	Blocks HER2 dimerization	Breast (HER2+)	Same as trastuzumab (diarrhea worse)
Bevacizumab (Avastin)	VEGF	Anti-angiogenesis	Colon, lung, RCC, glioblastoma, ovarian	Hypertension, hemorrhage, thromboembolism, wound healing, GI perforation
Cetuximab	EGFR	EGFR signaling blockade	Colorectal (KRAS wild-type), head/neck	Acneiform rash, hypomagnesemia, infusion reaction
Panitumumab	EGFR	Same as cetuximab (fully human)	Colorectal (KRAS/NRAS wild-type)	Same rash (less infusion reaction)

Immune Checkpoint Inhibitors

Drug	Target	Mechanism	Indications	Key Toxicities (Immune-Related)
Ipilimumab (Yervoy)	CTLA-4	Blocks CTLA-4, enhances T-cell activation	Melanoma, RCC, MSI-H colorectal	Colitis (severe), hypophysitis, hepatitis, dermatitis
Nivolumab (Opdivo)	PD-1	Blocks PD-1, restores anti-tumor T-cells	Melanoma, NSCLC, RCC, Hodgkin, H&N, UC, HCC	Pneumonitis, colitis, hepatitis, thyroiditis, dermatitis, nephritis
Pembrolizumab (Keytruda)	PD-1	Same as nivolumab	Melanoma, NSCLC, H&N, MSI-H tumors, many others	Similar to nivolumab
Atezolizumab (Tecentriq)	PD-L1	Blocks PD-L1, prevents PD-1/PD-L1 interaction	NSCLC, UC, breast (TNBC), HCC	Similar to anti-PD-1 (less thyroiditis)
Durvalumab (Imfinzi)	PD-L1	Same as atezolizumab	NSCLC (consolidation after chemoradiation)	Similar

Hormonal Therapy

Drug Class	Mechanism	Cancer	Key Adverse Effects
Tamoxifen	SERM (estrogen receptor antagonist in breast)	Breast (ER+), pre- and post-menopausal	Hot flashes, DVT/PE, endometrial cancer, cataract
Aromatase inhibitors	Inhibit peripheral aromatase (androgen to estrogen)	Breast (ER+), post-menopausal only	Arthralgia, osteoporosis, fractures, hot flashes
Anastrozole/letrozole/exemestane	3rd-gen AI	Same	Same as above
Leuprolide/goserelin	GnRH agonist (suppresses FSH/LH after flare)	Prostate, premenopausal breast	Hot flashes, impotence, osteoporosis, gynecomastia
Abiraterone	CYP17A1 inhibitor (blocks adrenal androgen synthesis)	Castration-resistant prostate	Hypermineralocorticoidism (HTN, hypokalemia, edema), hepatotoxicity
Enzalutamide	Androgen receptor antagonist	Castration-resistant prostate	Fatigue, hypertension, seizure risk (rare)

Adverse Effect Management

Adverse Effect	Causative Agents	Management
Myelosuppression (neutropenia)	Most cytotoxics, especially carboplatin, docetaxel, anthracyclines	G-CSF (filgrastim, pegfilgrastim) for febrile neutropenia prophylaxis; dose delay/reduction
Anemia	Platinum, alkylating agents	Erythropoiesis-stimulating agents (ESA), blood transfusion; iron supplementation
Thrombocytopenia	Carboplatin, gemcitabine, alkylating agents	Platelet transfusion if <10,000-20,000; TPO-receptor agonists (romiplostim, eltrombopag)
Nausea/vomiting	Cisplatin (highly emetogenic), cyclophosphamide, anthracyclines	Antiemetics: 5-HT3 (ondansetron), NK1 (aprepitant), dexamethasone, olanzapine
Mucositis/stomatitis	5-FU, methotrexate, doxorubicin, etoposide	Oral care, cryotherapy (melphalan), palifermin (KGF), laser photobiomodulation
Diarrhea	Irinotecan, 5-FU/capecitabine, TKIs	Loperamide (early diarrhea); octreotide (severe); atropine for early cholinergic diarrhea (irinotecan)
Hand-foot syndrome	Capecitabine, 5-FU (continuous infusion), liposomal doxorubicin, sunitinib, sorafenib	Dose interruption, cool soaks, emollients, pyridoxine (limited data)
Cardiotoxicity	Doxorubicin (anthracyclines), trastuzumab	Limit cumulative dose; dexrazoxane (cardioprotectant); LVEF monitoring
Peripheral neuropathy	Cisplatin, oxaliplatin, paclitaxel, docetaxel, vinca alkaloids, bortezomib	Dose reduction, pregabalin/gabapentin, duloxetine, TENS
Renal toxicity	Cisplatin, methotrexate (high dose), ifosfamide	Hydration, magnesium supplementation, avoid nephrotoxins
Hemorrhagic cystitis	Cyclophosphamide, ifosfamide	Mesna (sodium 2-mercaptoethane sulfonate), aggressive hydration

Conclusion

Chemotherapy and anticancer pharmacology encompass a rapidly evolving array of cytotoxic, targeted, immunotherapeutic, and hormonal agents. While traditional cytotoxic drugs remain important, the field is increasingly driven by molecular profiling, biomarker selection, and immunotherapy combinations. Adverse effect management and supportive care have significantly improved patient tolerance and outcomes. Emerging areas include antibody-drug conjugates, bispecific antibodies, CAR-T cell therapy, and combination immunotherapy approaches.