Lecture 14 Flashcards
Chemotherapy
Remission
Absence of detectable disease. Often achieved after 1-2 courses of chemotherapy.
When are patients with malignancies often the sickest?
When they initially present
What do most malignancies require for remission and long term survival?
Aggressive Chemotherapy
What risk does chemotherapy carry?
Considerable risk of toxicity. Managed by appropriate scheduling and use of adjunct medications.
Are children considered small adults?
No.
Pre-B Cell
Refers to the cellular lineage where the leukemia developed. Lymphocytic leukemia may develop in either the B-cell or the T-cell lineage.
Blasts
Immature cells with no function
Erythroid Precursors
RBC precursors
Neutrophil Precursors
Metamyelocytes, promyelocytes, myelocytes
Segs
Segmented polymorphonuclear leukocytes or mature neutrophils
DNA Index
A value denoting the relative number of chromosomes. Patients with a value of 1.0 have 46 chromosomes. A patient with a DNA index of 1.5 would have 1.5 x 46 or 69 chromosomes. Abnormal chromosome content is restricted to the malignant cell line
Nadir
Lowest blood count following chemotherapy (typically for WBCs)
Induction
1st phase of chemotherapy - given to obtain a complete remission
Consolidation
Some chemotherapy regimens (leukemia for example) include this second phase, which is a period of intensified chemotherapy designed to kill tumor cells that aren’t eliminated by induction therapy.
Maintenance
Used to kill any remaining tumor cells, essential component of acute lymphoblastic leukemia regimens
Course
1 “round” of chemotherapy, usually consists of a set of chemotherapy drugs given over 1-2 weeks
Dose Limiting Toxicity (DLT)
-Toxicity that limits the dose per course or the frequency in which courses of chemotherapy can be administered
Translocations
Switching of portions of chromosomes
General Principles of Cancer Chemotherapy (5)
- Use of combination chemotherapy
- Use chemotherapy agents with non-overlapping toxicity whenever possible
- Some toxicities recover quickly (myelosuppression)
- Some toxicities recover slowly if at all (nephro or neurotoxicity)
- Use maximally tolerated doses of chemotherapy
Use of Combination Chemotherapy
- Use of drugs with different mechanisms of action
- Use of drugs with activity in the particular malignancy
Use Maximally Tolerated Doses
Dose reduction will affect (Reduce) overall survival (cure) but often will not affect remission. Adjust doses to give the patient the best chance for “cure” or long term survival, try to avoid intolerable toxicity.
Cancer’s Cure Definition
Return to the length of survival that the patient would have if they never had cancer.
Common Chemotherapy Toxicities (4)
- Myelosuppression
- Alopecia
- Nausea/Vomiting (N/V)
- Tumor Lysis Syndrome (TLS)
Myelosuppression
- Can result in neutropenia, thrombocytopenia, and anemia
- Neutropenia & thrombocytopenia occur initially
- Anemia occurs week to months later
- Can also occur from disease itself like in cancers like leukemia
Neutropenia
- Causes a significant risk of infection
- Risk determined by absolute neutrophil count (ANC)
- ANC = WBC * %seg + %bands
- ANC < 1000 = increases risk for infection, ANC < 500 = substantial risk for infection, ANC < 100 = virtually all patients will be infections
- The longer the neutropenia lasts the greater the risk for infection
Thrombocytopenia
- Increased risk of bleeding, especially if counts drop below 20 X 10/mm.
- Utilize transfusions since no CSF is available
Anemia
- Hct < ~30%
- Fatigue pallor, S.O.B., morality
Management of Myelosuppression
- Schedule chemotherapy every 2-3 weeks to allow for platelet and neutrophil recovery
- Give aggressive IV antibiotic regimens for patients who develop fever and neutropenia after chemotherapy (usually hospitalized)
- Consider prevention f myelosuppression by utilizing CSF and given in a prophylactic manner after chemotherapy and until neutrophil recovery achieved.
Darbepoetin & Epoetin
- Given throughout chemotherapy
- Epoetin every week and darbepoetin every 2-3 weeks
- Alternative to RBC transfusions and not approved for use in children
Problem with Epoetin and Darbepoetin
- In certain cancers the use of these drugs can cause cancer progression
- Not indicated for patients receiving myelosuppressive therapy
Alopecia
- Loss of hair
- Will re-grow following completion of chemotherapy
Nausea/Vomiting
- Among the most problematic of toxicities from a patient’s perspective
- Linked to refusal of curative chemotherapy
- Can be acute or delayed
- Even with appropriate management, patients may vomit 20+ times per course
N/V Severity Factors (3)
- Age: decreased symptoms in the very old and very young
- Alcohol: decreased symptom in those with history of increased alcohol consumption
- Chemotherapy: certain chemotherapies increase the likelihood of experiencing this symptom (platinum, high-dose alkylating agents)
Nausea Pathology
- Poorly understood
- Animal models provide insight and demonstrate action by cannabinoids
- Endogenous cannabinoids = similar effects
- Corticosteroids also had good anti-nausea activity, mechanism explaining why remained elusive however
N/V Management
- Often prevented or reduced with drug therapy (antiemetics)
- Most effective are 5-HT (serotonin) antagonist (zofran) and corticosteroids (dexamethasone)
- Newer agents include NK-1 (bradykinin) antagonists
- Antiemetics are more effective at preventing vomiting than controlling nausea
- Control of N/V from severely emetogenic chemotherapy or in the delayed phase is still challenging though
TLS
- Tumor Lysis Syndrome
- Defined as a combination of two or more metabolic derangements occuring in patients with cancer
- Commonly prior to or within 1-5 days of initiating chemo for leukemias and lymphomas
- Most commonly associated with Non-Hodgkin’s lymphoma and acute leukemias
Metabolic Derrangements
- Hyperuricemia
- Hyperkalemia
- Hypocalcemia
- Hyperphosphatemia
TLS Pathophysiology
- Begins with massive lysis of malignant cells
- Leads to rapid breakdown of nucleotide precursors from these cells to hypoxanthine and xanthine with subsequent conversion to uric acid
- Cellular lysis also results in the release of electrolytes, including potassium and phosphate which can lead to serious electrolyte disturbances and possible renal failure
TLS Prevention
- Usually can be prevented with Allopurinol, IV hydration, and possible alkalinization on first week of chemo
- Allopurinol inhibits xanthine oxidase and the conversion of xanthine to uric acid
- Alkalinization is controversial
- Those with high risk of TLS (high levels of uric acid, large tumor burdens, and renal dysfunction) may not respond to these methods and may require the use of Rasburicase instead
Rasburicase
Lyses uric acid into allantoin and hydrogen peroxide
Immunotherapy Changes
As more immunotherapy agents are incorporated into cancer treatment, the spectrum of toxicities will change from N/V, myelosuppression,
and alopecia to skin, colonic, hepatic, endocrine.
M3 AML
- All-trans retinoic acid for acute promyelocytic leukemia
- Causes blasts to mature into normal cells
- Not curative for all patients yet, but is a marked improvement in remission and survival when combined with chemo
Imatinib
- Inhibits BCR-ABL tyrosine kinase, abnormal gene product of Philadelphia chromosome in CML
- Blocks proliferation and induces apoptosis of cell
Is cost a problem when dealing with cancer treatment and prevention?
Yes, extremely. Oncologics is the most expensive therapeutic classes in the U.S.
