SM_276b: Chemotherapy Basics Flashcards
Describe systemic therapy for cancer
Systemic therapy is one of the major cancer treatment modalities
- Reduce tumor size: can promote resection
- Treat micro-metastatic disease: decreasing relapse
- Prolong survival
- Can be a curative treatment modality
- Chemotherapy: cytotoxic, teratogenic, carcinogenic
- Cancer treatment is fluid
Describe the drug development process
Drug development process
- Drug discovery
- Preclinical research
- Phase 1
- Phase 1
- Phase 3
- FDA approval (may be done earlier with accelerated FDA approval or adaptive trial design)
- Phase 4
Describe Phase I studies
Phase I studies
- Goal: define toxicity (dose limiting doxicity, maximum tolerated dose)
- Patient population: typically refractory patients, various tumor types
- Dose escalation studies: often use a 3+3 design
- Key characteristics: low number of patients, multiple doses used, toxicity endpoints
Describe Phase II studies
Phase II studies
- Goals: provide general response rates at maximal tolerated dose, provide additional safety data
- Patient population: small group of patients with specific tumor type
- Key characteristics: more but not a ton of patients, may not provie clinical benefit
Describe Phase III studies
Phase III studies
- Goal: efficacy in a specific line of therapy
- Patient population: large cohort with specific type of cancer at same level of treatment
- Key characteristics: large number of patients, usually a RCT with set control, gold standard points for assessment (overall survival, progression free survival)
Describe Phase IV studies
Phase IV studies
- Post-market safety monitoring
- Studies completed after drug has been FDA approved
- Long term effect
- Key characteristics: enormous number of patients, retrospective or FDA dictated RCT, gold standard points for assessment
Describe types of cancer treatment
Cancer treatment: CREST
- Chemo
- Radiation
- Endocrine therapy
- Surgical intervention
- Targeted therapy
- Immune therapy
Describe chemotherapy basics
Chemo basics
- Goal: cure vs palliation
- Requirements: killing most cancer cells, control most cancer cells, differentiation of cancer cells
- Mechanism: exploit differences between cancer cells and normal host cells to develop anti-cancer agents
Describe combination chemo
Combination chemo
- Used to overcome inherent drug resistance to single agents, delay / prevent acquired resistance
- Which agonists?: single agent activity against tumor, differing mechanisms of action, non-overlapping toxicities
Describe neoadjuvant and adjuvant treatment
- Neoadjuvant: given prior to removal of the tumor, to decrease tumor size in order to increase likelihood of complete resection
- Adjuvant: given after removal of tumor, to eliminate micro-metastatic tumor deposits and decrease risk of tumor recurrence
Describe concurrent therapy
Concurrent therapy
- Two treatment modalities at same time: chemo + radiation
- Chemo radio sensitizes tumor to increase tumor killed
- Increased risk of toxicities
Describe maintenance therapy
Maintenance therapy
- After initial chemo treatment
- Delays return of tumor
- Less return of toxicities
Describe remission induction
Remission induction
- First course of chemo in hematologic cancers
- To eradicate 99% of initial tumor burden and restore normal hematopoiesis and performance status
Describe consolidation therapy
Consolidation therapy
- During remission
- Administered at high level of intensity
- To reduce leukemic burden and decrease likelihood of relapse
____ and ____ are important dosing considerations
Dose intensity and density are important dosing considerations
Describe doxorubicin + cyclophosphamide dosing
Doxorubicin + cyclophosphamide dosing
- Traditional dosing: doxorubicin 60 mg/m2 IVP on day 1 + cyclophosphamide 600 mg/m2 IV on Day 1 of every 21 day cycle
- Dose dense: doxorubicin 60 mg/m2 IVP on day 1 + cyclophosphamide 600 mg/m2 IV on Day 1 of every 14 day cycle
Pharmacokinetics is ___
Pharmacokinetics is what body does to drug
- ADME: absorption, distribution, metabolism, and excretion
Pharmacodynamics is ___
Pharmacodynamics is what drug does to the body
Describe cell cycle
Cell cycle
- G0: cell cycle arrest
- G1: cellular contents, excluding chromosomes, are duplicated
- S: each of 46 chromosomes is duplicated by the cell
- G2: cell double checks the duplicated chromosomes for error and makes repairs
- Mitosis
- Cytokinesis
___ is a chemotherapeutic agent that targets G1
Asparaginase is a chemotherapeutic agent that targets G1
___ and ___ are chemotherapeutic agent that target S
Antimetabolites and topoisomerase-I inhibitors are chemotherapeutic agents that target S
___ and ___ are chemotherapeutic agents that target G2
Epipodophyllotoxins and anthracenediones are chemotherapeutic agents that target G2
____ are chemotherapeutic agents that target M
Antimicrotubule agents are chemotherapeutic agents that target M
Describe chemotherapy classes
Chemotherapy classes
___ and ___ are cell cycle nonspecific chemotherapeutic agents
Alkylating agents and anthracyclines are cell cycle nonspecific chemotherapeutic agents