Chemotherapy Explained: How It Works, Drug Classes, Side Effects, and Coping Strategies

Chemotherapy uses cytotoxic drugs to kill rapidly dividing cells—primarily cancer, but also affecting healthy tissues like bone marrow, GI mucosa, hair follicles, and gonads. It's systemic: it reaches cancer anywhere in the body.

Mechanism of Action

Drugs damage DNA or disrupt mitosis → apoptosis (programmed cell death). Cancer cells, with defective checkpoints, die preferentially. Effectiveness depends on growth fraction, drug sensitivity, and the tumor microenvironment.

Major Drug Classes

Class	Mechanism	Examples	Key Toxicities
Alkylating agents	DNA cross-linking	Cyclophosphamide, cisplatin, carboplatin, melphalan	Myelosuppression, nausea, infertility, second malignancies
Antimetabolites	Inhibit DNA/RNA synthesis	Methotrexate, 5-FU, gemcitabine, cytarabine, pemetrexed	Mucositis, myelosuppression, hepatotoxicity (MTX), neuropathy (gem)
Anthracyclines	Topo II inhibition, ROS	Doxorubicin, epirubicin, daunorubicin	Cardiotoxicity (cumulative dose), alopecia, myelosuppression
Taxanes	Stabilize microtubules → mitotic arrest	Paclitaxel, docetaxel, cabazitaxel	Neuropathy, myelosuppression, hypersensitivity (paclitaxel)
Vinca alkaloids	Inhibit microtubule assembly	Vincristine, vinblastine, vinorelbine	Neuropathy, constipation, SIADH (vincristine)
Topoisomerase inhibitors	Topo I/II inhibition	Irinotecan, topotecan (Topo I); Etoposide, teniposide (Topo II)	Diarrhea (irinotecan), myelosuppression
Platinum analogs	DNA adducts	Cisplatin, carboplatin, oxaliplatin	Nephrotoxicity (cis), neuropathy (oxali), ototoxicity (cis)
Antitumor antibiotics	DNA intercalation	Bleomycin, dactinomycin, mitomycin	Pulmonary fibrosis (bleo), skin/mucosal toxicity

Common Side Effects and Management

• Nausea/vomiting: 5-HT3 (ondansetron), NK1 (aprepitant), dexamethasone, olanzapine – prophylaxis per emetogenic risk
• Alopecia: Scalp cooling (caps) reduces; regrowth post-treatment
• Myelosuppression: Nadir 7–14 days. G-CSF (filgrastim/pegfilgrastim) for febrile neutropenia prevention. Transfusions if symptomatic.
• Mucositis: Oral hygiene, magic mouthwash, palifermin (stem cell transplant)
• Peripheral neuropathy: Duloxetine (prevention/treatment), gabapentin, cryotherapy (taxanes/platinum)
• Fatigue: Exercise (paradoxically helps), treat anemia, sleep hygiene
• Fertility preservation: Sperm/egg/embryo freezing BEFORE treatment. Gonadal shielding.

Combination Strategies

• Chemo + Radiation: Concurrent (radiosensitization) or sequential. Organ preservation (anal, cervical, H&N, lung).
• Chemo + Targeted: Trastuzumab (HER2+), bevacizumab (VEGF), rituximab (CD20)
• Chemo + Immunotherapy: Checkpoint inhibitors (PD-1/PD-L1) + chemo → standard in many (lung, TNBC, gastric, urothelial)
• Neoadjuvant (pre-surgery): Downstage, assess response (pCR = prognostic), enable breast conservation
• Adjuvant (post-surgery): Eradicate micrometastases

Quality of Life and Coping

• Palliative care integration early → improved QOL, reduced depression, may improve survival
• Exercise during treatment (ONS guidelines) – reduces fatigue, neuropathy, anxiety
• Nutrition: Protein, calories, hydration. Dietitian access.
• Psychosocial: Support groups, counseling, financial navigation, spiritual care
• Fertility, sexual health, body image – address proactively

Future: Precision Chemotherapy

Biomarker-driven (HRD, MSI, TMB, NTRK, HER2), ADCs (antibody-drug conjugates: trastuzumab deruxtecan, sacituzumab govitecan, enfortumab vedotin) – targeted chemo delivery. Less toxicity, more efficacy.

Chemotherapy remains curative for many cancers. Understanding it demystifies the journey.