====== Combination Therapy ======

**Combination therapy** refers to the use of **two or more therapeutic agents or modalities** simultaneously or sequentially to treat a disease, aiming to enhance efficacy, reduce resistance, and improve patient outcomes.

===== Objectives =====
  * **Synergistic effect**: Achieve greater therapeutic impact than with monotherapy
  * **Target multiple pathways**: Interrupt tumor growth, survival, or resistance mechanisms
  * **Delay resistance**: Reduce the likelihood of tumor adaptation to single agents
  * **Lower doses**: Reduce toxicity by using lower doses of each component

===== Types of Combination Therapy =====
  * **Drug + Drug**:
    * EGFR inhibitor + Chemotherapy (e.g., Gefitinib + Cisplatin)
    * Immunotherapy + Antiangiogenic agent (e.g., Nivolumab + Bevacizumab)
  * **Drug + Radiotherapy**:
    * Radiation + EGFR inhibitor (e.g., Cetuximab + Radiotherapy in HNSCC)
  * **Targeted + Immunotherapy**:
    * EGFR-TKI + PD-1/PD-L1 inhibitor (under investigation)
  * **Multimodal (surgery, chemo, radio)**:
    * Glioblastoma: Surgical resection + Radiotherapy + Temozolomide

===== Clinical Applications =====
  * **Oncology**:
    * Lung cancer, breast cancer, glioblastoma, colorectal cancer
  * **Infectious diseases**:
    * HIV, tuberculosis, malaria
  * **Chronic diseases**:
    * Hypertension, diabetes

===== Considerations =====
  * **Pharmacokinetic and pharmacodynamic interactions**
  * **Increased risk of toxicity**
  * **Sequential vs. simultaneous administration**
  * **Cost-effectiveness and patient compliance**

===== Example: Combination in EGFR+ NSCLC =====
  * First-line: [[oncology:egfr_tki|EGFR-TKI]] (e.g., Erlotinib)
  * Resistance phase: Add **anti-MET** agent or **immune checkpoint inhibitor**
  * Investigational: EGFR-TKI + **anti-VEGF** or **ALK inhibitor** in co-mutated tumors

===== Related Topics =====
  * [[oncology:monotherapy|Monotherapy]]
  * [[oncology:drug_synergy|Drug Synergy]]
  * [[oncology:egfr_inhibitor|EGFR Inhibitors]]
  * [[oncology:immunotherapy|Immunotherapy]]
  * [[pharmacology:adverse_effects|Adverse Effects and Toxicity]]