Classification of Chemotherapy Drugs for Adult Cancer Patients
Chemotherapy drugs should be classified into five major mechanistic categories: alkylating agents, antimetabolites, anthracycline antibiotics, plant alkaloids (including taxanes and vinca alkaloids), and topoisomerase inhibitors, with selection based on cancer histology, prior treatment exposure, and specific toxicity profiles. 1
Primary Classification by Mechanism of Action
Alkylating Agents
- Platinum compounds (cisplatin, carboplatin, oxaliplatin) form DNA crosslinks and are preferred for lung, ovarian, testicular, and colorectal cancers 2, 3
- Carboplatin is generally better tolerated than cisplatin with easier administration, making it the preferred platinum agent for many patients 4
- Cyclophosphamide is used primarily in breast cancer combination regimens (AC, CAF/FAC, FEC) 5
Antimetabolites
- Fluoropyrimidines (5-fluorouracil, capecitabine) inhibit thymidylate synthase and are foundational for colorectal, gastric, and breast cancers 2
- Gemcitabine is preferred for pancreatic, lung, and breast cancers with response rates of 28-30% in metastatic breast cancer 2
- Pemetrexed is specific for non-squamous non-small cell lung cancer and requires mandatory vitamin B12 (1000 μg IM every 9 weeks) and folic acid (0.4-1.0 mg daily) supplementation 4
Anthracycline Antibiotics
- Doxorubicin (60-75 mg/m² every 3 weeks or 20 mg/m² weekly) achieves 30-47% response rates in breast cancer but carries significant cardiotoxicity risk 2
- Epirubicin is used in breast cancer regimens (FEC, ECF) with lower cardiotoxicity than doxorubicin 2
- Liposomal doxorubicin (50 mg/m² every 4 weeks) reduces cardiotoxicity from 26% to 7% compared to conventional doxorubicin, though increases palmar-plantar erythrodysesthesia risk 2
Plant Alkaloids
Taxanes:
- Paclitaxel administered weekly (80 mg/m²) improves overall survival compared to every-3-week dosing (HR 0.78; 95% CI 0.67-0.89) in advanced breast cancer 2
- Docetaxel (75-100 mg/m² every 3 weeks) is preferred for breast, lung, and gastric cancers with 86% grade 3-4 neutropenia at higher doses 2
- Sequential anthracycline-taxane regimens are superior to concomitant administration 2
Vinca Alkaloids:
- Vinorelbine (25-30 mg/m² weekly) is used for non-small cell lung cancer with 82% grade 3-4 neutropenia when combined with cisplatin 2
Microtubule Inhibitors:
- Eribulin is reserved for metastatic breast cancer after at least 2 prior chemotherapy regimens 2
Topoisomerase Inhibitors
- Irinotecan (125 mg/m² weekly) causes 54% grade 3-4 neutropenia when combined with fluorouracil-leucovorin in colorectal cancer 2
- Topotecan is used for recurrent small-cell lung cancer with 70% grade 3-4 neutropenia 2
Classification by Cancer Type and Clinical Context
Breast Cancer Hierarchy
Preferred single agents: taxanes (paclitaxel), anthracyclines (doxorubicin, liposomal doxorubicin), capecitabine, gemcitabine, eribulin, vinorelbine 2
HER2-positive disease: Trastuzumab combined with chemotherapy halves recurrence risk and must not be given concomitantly with anthracyclines due to cardiotoxicity 2
Triple-negative disease: Platinum agents (carboplatin, cisplatin) are preferred for patients with germline BRCA1/2 mutations 2
Lung Cancer Stratification
Non-squamous NSCLC: Carboplatin/pemetrexed/pembrolizumab is standard first-line treatment 4
Squamous cell carcinoma: Paclitaxel (175 mg/m² over 3 hours) plus cisplatin (100 mg/m²) or docetaxel/cisplatin/5-FU regimens 2
Gastrointestinal Cancers
Colorectal cancer: FOLFOX (oxaliplatin 85 mg/m² plus leucovorin/5-FU) causes 44-53% grade 3-4 neutropenia 2, 3
Gastric/esophageal cancer: ECF (epirubicin/cisplatin/5-FU), DCF (docetaxel/cisplatin/5-FU), or modified DCF regimens are preferred, with DCF modifications favored over standard DCF 2, 5
Critical Toxicity-Based Considerations
Myelosuppression Risk Stratification
High-risk regimens (>20% febrile neutropenia): TAC, BEACOPP, RICE require primary G-CSF prophylaxis 6, 5
Moderate-risk regimens: Docetaxel monotherapy (65-86% grade 3-4 neutropenia), gemcitabine/cisplatin (57% grade 3-4 neutropenia) 2
Nadir timing: Blood counts typically reach lowest levels on days 8 and 15 of each cycle, requiring monitoring at these intervals 4, 5
Organ-Specific Toxicities
Cardiotoxicity: Anthracyclines should not be combined with trastuzumab; liposomal formulations reduce cardiac risk 2
Neurotoxicity: Platinum agents and taxanes cause cumulative peripheral neuropathy requiring dose modifications 5, 3
Nephrotoxicity: Cisplatin and high-dose methotrexate require aggressive pre/post-hydration protocols 5
Pulmonary toxicity: Pembrolizumab can cause pneumonitis requiring immediate evaluation for new respiratory symptoms 4
Practical Administration Algorithm
Dose-Dense vs. Standard Scheduling
Dose-dense schedules (every 2 weeks with G-CSF support) should be considered for highly proliferative tumors 2, 5
Combination Therapy Principles
- Sequential anthracycline-taxane administration is superior to concomitant use 2
- Two-drug regimens are preferred over three-drug combinations except in medically fit patients with good performance status 2
- Continuous chemotherapy until progression improves progression-free survival (HR 0.66; 95% CI 0.6-0.72) compared to limited cycles 2
Renal Impairment Adjustments
Oxaliplatin requires dose modifications for creatinine clearance <30 mL/min 3
Common Pitfalls to Avoid
Never use high-dose chemotherapy with stem cell support in breast cancer—it provides no survival benefit 2
Avoid aromatase inhibitors alone in premenopausal patients—no efficacy evidence exists without ovarian suppression 2
Do not start tamoxifen concurrently with chemotherapy—it should begin after chemotherapy completion 2
Monitor for immune-related adverse events months after pembrolizumab completion—colitis, pneumonitis, and other toxicities can occur late 4
Ensure vitamin supplementation before pemetrexed—starting B12/folic acid at least 1 week prior reduces severe toxicity risk 4