Antineoplastic agents are crucial in cancer chemotherapy, targeting rapidly dividing cells to slow or stop tumor growth. These drugs work through various mechanisms, from damaging DNA to disrupting cell division, and are often used in combination for maximum effect.

Understanding antineoplastic agents is key to grasping modern cancer treatment. While these drugs can be highly effective, they also come with significant side effects, making supportive care and targeted therapies important aspects of comprehensive cancer management.

Antineoplastic agents: Mechanism of Action and Target Specificity

Alkylating Agents and Antimetabolites

• Antineoplastic agents categorized into several classes based on mechanisms of action include alkylating agents, antimetabolites, topoisomerase inhibitors, mitotic inhibitors, and targeted therapies
• Alkylating agents directly damage DNA through alkylation preventing cell division
  • Cyclophosphamide and cisplatin exemplify this class
• Antimetabolites interfere with DNA and RNA synthesis by mimicking natural metabolites
  • Methotrexate inhibits dihydrofolate reductase disrupting folate metabolism
  • 5-fluorouracil acts as a pyrimidine analog inhibiting thymidylate synthase

Topoisomerase and Mitotic Inhibitors

• Topoisomerase inhibitors prevent DNA unwinding and replication by inhibiting topoisomerase enzymes
  • Irinotecan targets topoisomerase I
  • Etoposide inhibits topoisomerase II
• Mitotic inhibitors disrupt microtubule formation preventing cell division during mitosis
  • Paclitaxel stabilizes microtubules
  • Vincristine prevents microtubule polymerization

Targeted Therapies and Hormone Therapies

• Targeted therapies interfere with specific molecular targets involved in tumor growth and progression
  • Imatinib inhibits BCR-ABL tyrosine kinase in chronic myeloid leukemia
  • Trastuzumab targets HER2 protein in HER2-positive breast cancer
• Hormone therapies modulate hormone signaling pathways to treat hormone-dependent cancers
  • Tamoxifen acts as an estrogen receptor modulator in breast cancer
  • Leuprolide suppresses testosterone production in prostate cancer

Combination chemotherapy: Principles for cancer treatment

Rationale and Design of Combination Therapy

• Combination chemotherapy uses multiple antineoplastic agents with different mechanisms of action to enhance overall treatment efficacy
• Targeting different cellular pathways reduces drug resistance and potentially lowers individual drug doses minimizing toxicity
• Synergistic effects between drugs lead to improved tumor cell kill rates compared to single-agent treatments
• Combination regimens balance maximal therapeutic effect with acceptable toxicity profiles
• Sequencing of drugs in combination therapy affects both efficacy and side effect profiles

Examples and Development of Combination Regimens

• Common combination regimens exemplify diverse approaches
  • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) treats lymphomas
  • FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) addresses colorectal cancer
• Development of new combination strategies involves clinical trials determining optimal drug combinations, dosing schedules, and treatment durations
  • Phase I trials establish safety and maximum tolerated doses
  • Phase II trials assess efficacy in specific cancer types
  • Phase III trials compare new combinations to standard treatments

Adverse effects of chemotherapy

Hematological and Gastrointestinal Toxicities

• Myelosuppression leads to anemia, neutropenia, and thrombocytopenia
  • Neutropenia increases infection risk
  • Thrombocytopenia may cause bleeding complications
• Gastrointestinal toxicities frequently observed with various chemotherapy regimens
  • Nausea and vomiting impact quality of life and nutrition
  • Mucositis causes painful inflammation of the digestive tract lining

Dermatological, Cardiac, and Neurological Effects

• Alopecia (hair loss) occurs with many antineoplastic agents
  • Affects scalp hair, eyebrows, and body hair
• Cardiotoxicity particularly associated with anthracyclines like doxorubicin
  • Can lead to long-term cardiac complications (cardiomyopathy)
• Neurotoxicity manifests as peripheral neuropathy with certain drug classes
  • Platinum compounds (cisplatin) cause sensory neuropathy
  • Taxanes (paclitaxel) induce both sensory and motor neuropathy

Organ-specific Toxicities and Long-term Consequences

• Hepatotoxicity and nephrotoxicity occur with specific agents
  • Methotrexate can cause liver damage
  • Cisplatin may induce kidney injury
• Secondary malignancies develop as a long-term consequence of certain chemotherapeutic agents
  • Alkylating agents increase risk of acute myeloid leukemia
  • Topoisomerase II inhibitors associated with treatment-related leukemias

Supportive care in cancer chemotherapy

Antiemetic Therapy and Hematopoietic Support

• Antiemetic therapy manages chemotherapy-induced nausea and vomiting
  • Ondansetron (5-HT3 receptor antagonist) prevents acute emesis
  • Aprepitant (NK1 receptor antagonist) controls delayed emesis
• Growth factors manage myelosuppression reducing infection and anemia risk
  • G-CSF (filgrastim) stimulates neutrophil production
  • Erythropoietin boosts red blood cell production

Pain Management and Nutritional Support

• Pain management strategies improve quality of life during cancer treatment
  • Opioid analgesics (morphine) control moderate to severe pain
  • Non-opioid analgesics (NSAIDs) address mild to moderate pain
• Nutritional support maintains patient strength and promotes recovery
  • Dietary counseling addresses treatment-related appetite changes
  • Enteral or parenteral nutrition supplements inadequate oral intake

Psychosocial Support and Symptom Management

• Psychosocial support addresses emotional and psychological impact of cancer and treatment
  • Counseling helps patients cope with diagnosis and treatment stress
  • Support groups provide peer support and shared experiences
• Management of treatment-related fatigue involves pharmacological interventions and lifestyle modifications
  • Methylphenidate may alleviate cancer-related fatigue
  • Exercise programs improve energy levels and physical functioning
• Proper dental care and oral hygiene prevent and manage chemotherapy-induced mucositis
  • Chlorhexidine mouthwash reduces oral bacterial load
  • Oral cryotherapy during chemotherapy may prevent mucositis

Targeted Therapies and Immunotherapy in Cancer Treatment

Monoclonal Antibodies and Small Molecule Inhibitors

• Targeted therapies interfere with specific molecular pathways involved in cancer growth and progression
  • Offer potentially more effective and less toxic treatment options
• Monoclonal antibodies target specific antigens on cancer cells
  • Rituximab targets CD20 on B-cell lymphomas
  • Trastuzumab blocks HER2 signaling in breast cancer
• Small molecule inhibitors block specific enzymes or receptors involved in cancer cell signaling and survival
  • Imatinib inhibits BCR-ABL in chronic myeloid leukemia
  • Erlotinib targets EGFR in non-small cell lung cancer

Immunotherapy Approaches

• Immunotherapy harnesses the body's immune system to fight cancer
• Checkpoint inhibitors block proteins preventing T cells from attacking cancer cells
  • Pembrolizumab inhibits PD-1 receptor
  • Nivolumab targets PD-1 pathway
• CAR T-cell therapy involves genetically modifying patient's T cells to target specific cancer antigens
  • Tisagenlecleucel treats B-cell acute lymphoblastic leukemia
  • Axicabtagene ciloleucel addresses certain types of non-Hodgkin lymphoma

Combination Strategies and Future Directions

• Combination strategies explore targeted therapies, immunotherapies, and traditional chemotherapies to improve outcomes
  • Combining checkpoint inhibitors with chemotherapy in non-small cell lung cancer
  • Integrating targeted therapies with hormone therapy in breast cancer
• Ongoing research focuses on identifying biomarkers for treatment response
  • PD-L1 expression guides checkpoint inhibitor use
  • Tumor mutational burden informs immunotherapy decisions
• Development of novel immunotherapy approaches continues
  • Bispecific antibodies engage T cells and tumor cells simultaneously
  • Cancer vaccines stimulate immune responses against tumor-specific antigens