Intro to oncology pt 2 Flashcards
Recall/learn these terms from Oncology Basics
• Neoadjuvant
• Adjuvant
• Palliative
TESTABLE
Neoadjuvant chemotherapy
• Use of chemotherapy prior to local treatment (surgery or radiation)
• Goal is usually to enhance the potential effectiveness of local treatment by reducing tumour burden
Tumor is big, give some radiation first before surgery
Adjuvant therapy
• Use of a treatment following a local treatment
• For potentially curable patients, goal is to destroy residual and/or undetectable tumour cells to prolong survival and/or reduce the risk of recurrence
Need chemo after the local surgery
Palliative therapy
• Use of a treatment to alleviate/reduce symptoms, stabilize disease/slow progression, and improve/maintain quality of life
chronic condition with no cure, can give treatmen t to make them feel better, tumor smaller, extend their life and quality
• Induction
• Consolidation
• Maintenance
define
Induction: inducing a remission, not often sustaiable (leukemia)
Consolidation: keep in remission, chemo
Maintenance: we will hold remission
Considerations in Choosing Pharmacotherapy
• Patient Factors
• Age
• A younger patient can often tolerate more intensive treatment
• A younger patient could be at higher risk for long term toxicities
• Performance Status (ECOG)
• ECOG is a scale of 0-5 to quantify performance status
• It helps inform how the disease is impacting a patient’s daily living abilities and inform treatment decisions
• Comorbidities
• Pre-existing medical conditions may influence drug selection
• Example if poor cardiac function (low EF) then avoid anthracyclines
• Substantial co-morbidities may impact patient’s lifespan and hence appropriateness and tolerance of aggressive therapy
Considerations in Choosing Pharmacotherapy
Disease Factors
• Cancer type, stage and grade
• Provides insight into possible treatment outcomes and aggressiveness
of the disease
• Molecular profiling - BIOMARKERS
• Provides insight into the prognosis of this patient’s specific disease type
and characteristics
• Provides insight into potential response to specific (often targeted)
agents – Personalized Medicine!
• Other prognostic factors:
• Many cancers have validated algorithms to estimate patient prognosis
Considerations in Choosing Pharmacotherap
• Drug/Medication Factors
• What is the standard of care based on:
• Published guidelines
• Institutional practices
• Primary literature
What is the toxicity profile of the standard of care?
Is modification required based on patient factors?
• Molecular profiling – Pharmacogenomics/genetics
• What is the evidence of the therapy’s efficacy with the specific molecular profiling of the patient’s disease?
• Cost/Availability
Considerations in Choosing Pharmacotherapy
• Treatment Goals:
• Cure?
• Extension of Life (Prolonging Survival)?
• Improved Quality of Life?
• Palliation?
• Considerations for goals:
• What does the evidence estimate is likelihood of the desired goal
for the patient’s specific disease?
• How do the patient factors influence this estimate?
• Patient Perspective
• Goals of Therapy:
• Cure
• Patient is cancer free and expected to have a life span
equivalent to the general population
• Keep in mind the following:
• Even though imaging, pathology, and laboratory tests can be used to
assess if disease is present, there can be undetectable microscopic
disease (micrometastases) present.
• Often measured in the literature/trials as “5 year disease free
survival”
• In other words, at 5 years after treatment, the patient is still alive and detectable cancer is still absent
• Goals of Therapy:
• 5 year disease free survival:
• Fictitious Example:
• In the XYZ trial of chemotherapy added to surgery, disease
free survival was 60% at 5 years
• In other words 60% of the patients in the trial were still alive
and had no detectable disease relapse 5 years after their
treatment
Goals of Therapy:
• Prolonging Survival
• If cure is not achievable, treatment can be used to
increase survival time and/or improve quality of life
• Antineoplastic pharmacotherapy use for prolonging
survival is often measured in the literature/trials as
“progression free survival” (PFS)
• the number/proportion of patients that are still alive
and free of disease progression
• Progression Free Survival:
• Fictitious Examples:
• In the WRX trial of a new oral therapy, progression free survival
at 2 years was 68% for the new therapy compared with 22% for those on the older therapy.
• In other words, after 2 years, 68% of patients that receive the new therapy are alive and their disease has not progressed
(32% have either died or progressed)
• In the HIJ trial of a new oral therapy, median progression free survival was at 29 months with the new therapy compared with 12 months with the older therapy
• In other words, half of patients in the trial receiving the new therapy had either progressed or died at 29 months whereas half of patients receiving the old therapy either progressed or dies at 12 months.
Where 50% of patients were hit
At 29 months 50% of pt died or got worse
More people are living
• What about overall survival (“OS”)?
• Cancer treatments can have significant toxicities
• Many trials will report “OS” as well
• The proportion of patients that are still alive at a specified time.
• Takes into account death of any cause
In the WRX trial of a new oral therapy, overall survival at 2 years was 75% for the new therapy compared with
46% for those on the older therapy.
• In the HIJ trial of a new oral therapy, median overall survival was at 32 months with the new therapy compared with 18 months with the older therap
• Improving/Maintaining Quality of Life
• Minimizing or managing treatment toxicities
• Organ toxicity (heart, lung, kidney, liver, brain)
• Nausea/vomiting
• Rash
• Changes to bowel habits (diarrhea or constipation)
• Mucositis
• Infection risk
• Minimizing or managing cancer symptoms
• Symptoms due to site of tumour. Examples:
• Breathing (lung, lymphoma)
• Endocrine function (pancreatic, thyroid)
• Cognitive function or seizure control (brain)
• Pain control
• End of life issues (palliative lecture)
Strategies for using Antineoplastics
• CONCEPT:
• Maximize cancer cell kill with antineoplastics while avoiding irreversible
toxicities
• In other words - balance maximizing cancer destruction with what the
human body can handle or recover from
• Consider strategies like dosing (intensity), frequency (density) and using
combination therapy
• Dosing
• Antineoplastic agents often have a narrow therapeutic window
• “dose limiting toxicity” – an agent’s specific toxicity(ies) that ultimatelycaps how much antineoplastic drug can be administered
• Dosing can be based on:
• Body Surface Area (“BSA”) - Common with cytotoxic chemotherapy
• Renal Function - example is Carboplatin based on Calvert Formula
• Flat dosing - Common with oral targeted agents
• Adjustments for organ function
• Specific recommendations may be set for adjustments based on renal
function, liver function, blood cell counts
Strategies for using Antineoplastics
• Frequency:
• Cytotoxic agents:
• The body needs appropriate time to recover after exposure to traditional cytotoxic agents. Hence, many agents are given cyclically!!
• Example: Chemo might be administered once every 14, 21, or 28 days (Wait 14, 21, 28 days to do it again)
• In practice we would say “Chemo administered on DAY 1 of a 21 day cycle)
• Targeted oral agents (small molecules)
• Many of these agents are administered daily for several consecutive days followed by a rest period.
• Targeted IV therapies (monoclonal antibodies)
• Administered IV cyclically (with chemo)
• Very long half life
Combination Therapies
• Concepts to maximize efficacy:
• Each drug must have clinical activity against the tumour alone
• Somewhat Obvious
• Each drug should have a different MOA
• Better cell kill if attacking cancer through various mechanisms, targets, and/or
stages of cell cycle
• Helps minimize the capacity for the cancer to mutate and acquire resistance
• The combinations should be synergistic
• Again, somewhat obvious
