What is chemotherapy?

What is Chemotherapy

Chemotherapy is a systemic cancer treatment that uses cytotoxic drugs to kill rapidly dividing cancer cells by interfering with DNA synthesis and cell division, though it also affects normal rapidly dividing cells, causing significant toxicity. 1, 2

Mechanism of Action

Chemotherapy drugs target cancer cells through several distinct mechanisms:

• Alkylating agents damage DNA directly, preventing cancer cells from reproducing 2
• Antimetabolites interfere with DNA and RNA synthesis by mimicking normal cellular building blocks 2
• Anthracycline antibiotics insert between DNA base pairs and inhibit topoisomerase enzymes 2
• Plant alkaloids (taxanes, vinca alkaloids) disrupt microtubule function during cell division 3, 2

The fundamental principle is that these drugs preferentially kill rapidly dividing cells, which includes cancer cells but unfortunately also normal tissues like bone marrow, gastrointestinal epithelium, and hair follicles 1, 4

Clinical Applications

Curative Intent

• Adjuvant chemotherapy is given after surgery to eliminate microscopic residual disease and reduce recurrence risk 3
• Neoadjuvant chemotherapy is administered before surgery to shrink tumors and improve surgical outcomes 3
• Primary treatment for chemotherapy-sensitive cancers like leukemias, lymphomas, and certain solid tumors 3

Palliative Intent

• Used in metastatic or recurrent disease to extend survival and control symptoms 3
• Treatment continues until disease progression or unacceptable toxicity 3

Common Regimens

Combination chemotherapy is preferred over single agents because it provides higher response rates and longer progression-free survival, though at the cost of increased toxicity 3

Breast Cancer

• Anthracycline-based regimens (AC, EC, FAC/CAF, FEC) followed by taxanes 3, 5
• Sequential administration of anthracyclines and taxanes is recommended over concurrent use 3
• Dose-dense schedules with G-CSF support should be considered for highly proliferative tumors 3

Bladder Cancer

• Cisplatin-based combinations (gemcitabine/cisplatin, MVAC) are standard for metastatic disease 3
• Carboplatin may substitute for cisplatin when glomerular filtration rate is <60 mL/min 3, 6

Head and Neck Cancer

• Cisplatin or carboplatin combined with 5-FU and cetuximab 3
• Docetaxel/cisplatin/5-FU for induction therapy 3

Major Toxicities and Management

Hematologic Toxicity

• Myelosuppression is the most common dose-limiting toxicity, requiring growth factor support (G-CSF) for high-risk regimens 5, 1
• Monitor complete blood counts regularly and adjust doses based on nadir counts 5

Gastrointestinal Toxicity

• Nausea and vomiting managed with 5-HT3 antagonists, NK1 antagonists, and dexamethasone based on emetogenic risk 5, 1
• Mucositis and diarrhea require supportive care and dose modifications 5, 2

Organ-Specific Toxicity

• Cardiotoxicity particularly with anthracyclines; trastuzumab should not be given concomitantly with anthracyclines 3, 2
• Nephrotoxicity with platinum agents requires adequate hydration and renal function monitoring 5, 7
• Neurotoxicity (peripheral neuropathy) common with taxanes and platinum agents 3, 1

Other Common Effects

• Alopecia, fatigue, infertility, and cognitive impairment ("chemo brain") 1, 2

Critical Treatment Principles

Duration and Response Assessment

• Reevaluate after 2-3 cycles and continue for 2 additional cycles if disease responds or remains stable 3
• Maximum of 6 cycles for metastatic disease unless complete resection is achieved 3
• Change therapy if no response after 2 cycles or significant toxicity develops 3

Sequential vs. Combination Therapy

• Sequential single-agent therapy is preferred over combination therapy for metastatic disease when rapid disease control is not required, as it decreases toxicity without compromising survival 3
• Combination therapy is reserved for patients requiring rapid symptom control or those with aggressive disease 3

Important Caveats

The therapeutic window is narrow—chemotherapy kills both cancer cells and normal rapidly dividing cells, making toxicity management critical 1, 4

Renal function assessment is essential before initiating platinum-based chemotherapy; use actual creatinine clearance (Cockcroft-Gault equation), not serum creatinine alone, especially in elderly patients 6, 7

Performance status determines treatment intensity—patients with poor performance status should receive less toxic regimens or palliative care 3, 6

Solid tumors are inherently more resistant to chemotherapy than hematologic malignancies due to biological differences in tumor microenvironment and drug resistance mechanisms 8