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Oncology Therapeutics > Intro to ChemoTX and Targeted Therapy > Flashcards

Intro to ChemoTX and Targeted Therapy Flashcards

1
Q

Cytotoxic Chemotherapy includes which classes ? (6)

A
  1. Alkylating agents
  2. platinums
  3. topoisomerase inhibs
  4. Antitumor antibx
  5. microtubule inhibs
  6. antimetabolites
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2
Q

Cell Cycle specific vs Non specific

  1. SPECIFC
    - Speak about cell kill capabiliities
    - increase cell kill by incr ____
    -Prolonged exposure or repeat doses often to allow what ?
  2. NON SPECIFIC
    -affects cells whether it’s ___ or ____
    -chemotx doenst have to be present during ___
    -Has ____
    -Incr cell kill by incr __
A
  1. Has a limit to cell kill bc only cells in that particular phase are killed
  • duration of chemotx exposure
  • more cells to enter the sensitive phase of the cycle
  1. proliferating, resting
    - a specific phase of the cell cycle
    - linear dose-response curve
    - dose
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3
Q

Which agents are CELL CYCLE SPECIFIC? (4)

A
  1. antimetabolites
  2. topo isom inhibs
  3. Microtubule inhibs
  4. antitumor abx : bleomycin
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4
Q

ANTIMETABOLITES
1. Maximal cytotoxic effects during which phase of cell cycle?
2. Name 6 antimetabs , their indications, and major ae’s

6
5
3
3
4
2

A
  1. S phase
  2. 5-FU
    colon cancer
    Mucositis, diarrhea, nausea, vomiting,hand-foot syndrome,myelosuppression
  3. Capecitabine (oral prodrug of 5fu)
    colon cancer
    Diarrhea, hand-foot syndrome, myelosuppression, nausea & vomiting, hyperbilirubinemia
  4. cytarabine
    - AML
    Myelosupp, ocular toxicity, cerebellar toxicity
  5. Fludarabine
    - bone marrow transplant
    - Myelosuppression, neurotoxicity, hand-
    foot syndrome (HFS)
  6. Methotrexate
    - Acute lymphoblastic leukemia , BMT
    - Mucositis!, nephrotoxicity, transaminitis, myelosuppression
  7. Pemetrexed
    lung cancer
    -myelosuppression, rash
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5
Q

Topoisomerase Inhibitors
1. Affects which stage of cell cycle?
2. name the 2 agents, what theyre clinically used for and their major AE’s

A
  1. S and G2
  2. Irinotecan –> colon cancer , Inhibs TOPO1
    Mucositis, diarrhea!!!!, nausea, vomiting, myelosuppression, fatigue
  3. Etoposide (inhibs TOPO II)
    - Lung cancer, NHL, BMT
    Nausea/vomiting, alopecia!!, myelosuppression
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6
Q

Irinotecan Induced Diarrhea :

  1. Acute
    -Onset ?
    -Additional cholinergic sx’s?
    -Severity of sx’s is ____
    -Prevention ?
  2. Delayed
    -Due to ?
    -Onset is ?
    -Tx?
A
  1. Observed during irinotecan infusion up to 24 hrs after the infusion
    - abdom cramping, diaphoresis, hypersalivation, visual changes, hyperlacrimation, rhinitis, flushing
    - dose-related
    -atropine 0.25 mg IV or SQ given prior to irinotecan infusion
  2. SN 38 metabolite
    - >=24h after infusion of irinotecan
    - Fluids/electrolytes, BRAT diet
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7
Q

Microtubule Inhibitors :
1. What are the 2 types ?

  1. Describe what each of them do
A
  1. Vinca alkaloids and Taxanes
  2. Vincas prevent microtubule assembly
    - taxanes prevent microtubule disassembly
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8
Q

For each, state what cancer theyre used for and major ae’s :

  1. Vincristine (5)
  2. Vinorelbine (2)
  3. vinblastine (3)
  4. docetaxel (3)
  5. paclitaxel (3)
A
  1. NHL, acute lymphoblastic leukemia
    Neutropenia,thrombocytopenia, peripheral neuropathy,constipation, NEUROTOXICITY
  2. Lung cancer, NHL
    Neutropenia, peripheral neuropathy
  3. Hodgkins lymphoma
    Leukopenia, alopecia, neuropathy
  4. Lung and breast cancer
    Neutropenia,thrombocytopenia, peripheral neuropathy
  5. Lung and breast cancer
    Neutropenia!!!, thrombocytopenia,
    peripheral neuropathy
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9
Q

Which Vinca alkaloids have more neurotoxicityand alopecia vs Mucositis/stomatitis and myelosuppression ?

WHich taxanes have more neurotoxicity+hypersensitivity rxns vs myelo+fluid retention ?

A

Neuro + Alopecia : Vincristine
Muco/myelo : Vinblastine/Vinorelbine

Neuro+Hypersensitivity : paclitaxel
Myelosupp+fluid retention : docetaxel

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10
Q

MICROTUBULE INHIBS AND NEUROPATHY

  1. Peripheral neuropathy
    -if severe or refractory cases of neuropathy what to do with chemo?
    -What can u consider?
  2. Autonomic neuropathy
    -presents as ?
    -This is ___ and ___
    -Use prophylatic ____
    -Whats an option for ileus treatment after ruling out possible bowel obstruction ?
A
  1. Discontinue chemo
    -dose reductions and delays
  2. constipation, urinary retention, impotence, and ortho hypo
    - cumulative, dose dependent
    - stool softeners
    -metoclopramide
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11
Q

BLEOMYCIN :

AE’s ?
1. Idiosyncratic rxn with sx’s such as ?
When does this occur?
How to test for this rxn?

  1. Pulm toxicity such as ? ***
    -Risk is higher in ?
  2. S H
  3. S
A
  1. Hypotension, mental confusion, fever, chills, and wheezing
    - after 1st or second dose
    -2 unit test dose –> observe x 1-2 hrs
  2. Pneumonitis, occasionally progressing to pulm fibrosis
    - elderly pt’s or pt’s receiving > 400 units total lifetime dose
  3. Skin hyperpigmentation
  4. Stomatitis
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12
Q

CELL CYCLE NON SPECIFIC

  1. WHich 3 agents?
A
  1. Anti tumor abx such as anthracyclines
  2. platinums
  3. alkylating agents
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13
Q

Anthracyclines : For the following name their indication, and major AE’s as a class

  1. Idarubicin
  2. Doxorubicin
  3. Daunorubicin
  4. These agents are ____ (central line)
A
  1. AML
  2. NHL, breast cancer, AML
  3. NHL

Myelosuppression
Nausea/vomiting
Mucositis
Alopecia
Cardiotoxicity!!!!!!!!!
Secondary malignancy
Extravasation

  1. Vesicants
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14
Q

Anthracyclines and Cardiotoxicity
1. What are the risk factors?
2. Prevention ? (2)
3. Monitoring
4. Whats the max lifetime dose in mg/m^2 for doxo, dauno, epi, mitoxantrone

A
  1. Cardiovasc disorder
    -concomitant cardiotoxic chemo
    -radiation to chest
    -cumulative lifetime dose
  2. Iron binder Dexrazoxane
    -Liposomal Formulations DOxil, DaunoXome
  3. LVEF with ECHO or MUGA scan before, during and after tx
    -calculate max lifetime dose
  4. 450-500
    400-550
    900
    140
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15
Q

Platinums : Cisplatin, Carboplatin, Oxaliplatin

What side effects do they have as a class? (6)

A
  1. Nephrotoxicity !!!!
    N/V
    Neuropathy (Cisplatin mainly)
    Ototoxicity (not oxaliplatin) !
    Myelosuppression (carboplatin mainly)
    Hypersensitivity
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16
Q

Cisplatin Induced Nephrotoxicity :

  1. Pt’s need hydration !
    -How much and when ?
    -Maintain UOP of ?
    -Monitor?
  2. What interferes w/anti tumor efficacy of Cisplatin?
  3. Mannitol (no compelling evidence that this could be nephron protective)
A
  1. 1-2 L for 2 hrs prior to and for 2 hrs after admin
    - > 100 mL/hr
    ie 1L NS + 10mEq KCL + 2 grams of Magnesium sulfate over 2h prior to chemotherapy and 1L NS + 10mEq KCL to run for 2h after chemotherapy
  • serum electrolytes (mag and potass), BUN/scr
  1. Amifostine
17
Q

Oxaliplatin related Acute neurotoxicity

  1. ACute sensory neurotoxicity
    -occurs in ?
    -When does it happen?
    -sx’s resolve when ?
    -Manifests as ?
A
  1. Nearly ALL patients
    -during or within hrs of infusion
    - 1 week but can recur with subsequent infusions

-Rapid Onset of cold-induced distal dysesthesia and or paresthesia sometimes accompanied by cold-dependent muscular contractions of the extremities or the jaw (know this)

18
Q

Oxaliplatin-related CHRONIC Neurotoxicity

  1. 10-15% of patients after ????
    -Non cold related ___ and ___ of the extremities
    -Sx’s are consistently ____
A
  1. cumulative doses of about 8-10 cycles

dysesthesias , paresthesias

reversible

19
Q

Alkylating Agents : For each agent state what its indications are and the major ae’s

  1. Cyclophosphamide
  2. Ifosfamide
  3. Dacarbazine
  4. Bendamustine
  5. CArmustine
  6. Busulfan
  7. Melphalan
A
  1. Breast cancer, NHL
  2. NHL
  3. HL
  4. HL
  5. BMT
  6. BMT

Mucositis
Myelosuppression
Nausea/vomiting
Infertility
Secondary malignancies

20
Q

Ifosfamide and Cyclophosphamide : Hemorrhagic Cystitis

  1. Sx’s
  2. Risk factors
  3. Prevention ?
A
  1. Hematuria, dysuria, urinary freq/urg, suprapubic pain
  2. Ifosfamide any dose
    -high dose of cyclophosphamide > 1 g/m^2
    -dehyration
    -renal impairment
  3. Hydration, frequent urination, Mesna
21
Q

Targeted Therapy Classes (2)?

A

Monoclonal Antibodies and signal transduction inhibs

22
Q

Monoclonal Antibodies , target, indication, and ae’s see chart

A

see chart

23
Q

Signal transduction inhibitors : Oral Targeted therapy for breast cancer

  1. Lapatinib
    -targets?
    -DDI?
    - FDA approval for ?
  2. Precautions and warnings
    -Decr in ___
    -H
    -D
    -P
    -P
  3. PK considerations? (2)
A
  1. HER2, EGFR
    - CYP 3a4 substrate
    -advanced/metastatic disease
  2. LVEF
    - hepatotoxic
    diarrhea
    penumonitis
    prolonged QT
  3. CYP 3A4 inhibs/inducers
    -hepatic impairment
24
Q

Oral targeted therapies : Lung cancer
State target and dosing

  1. Erlotinib
  2. Afatinib
  3. Gefitinib
  4. Osimertinib
A
  1. EGFR , 150 mg PO daily on empty stomach
  2. EGFR 40 mg PO daily on empty stomach
  3. EGFR with EXON 19 mut or exon 21 sub –> 250 mg PO daily with or without food
  4. EGFR T790M , 80 mg po daily with or without food
25
Q

Erlotinib : AE’s and DDIs/PK

  1. 7 ae’s
  2. Which enzyme is it an ihib or inducer for
  3. What kinda of drugs will decr erlotinib plasma concentrations
  4. what action decr erlotinib plasma concentrations?
A
  1. RASH
    * DIARRHEA
    * Anorexia
    * Fatigue
    * SOB
    * Cough
    * Nausea/vomiting
  2. CYP 3a4
  3. drugs affecting gastric pH such as PPI’s or h2ra’s
  4. cig smoking
26
Q

Prevention of EGFR inhib associated rash

  1. H, M, D
  2. TX of rash ? F, M, D
  3. Non pharm reccs?
A
  1. Hydrocortisone 1% cream w/moisturizer and suncreen BID AND minocycline 100mg daily or doxy 100 mg PO BID
  2. Fluocinonide 0.05% cream BID and minocycline 100mg daily or doxy 100 mg PO BID
  3. Cleaning w/mild soaps and BID moisturizing w/thick emoliient based creams
    -avoid prolonged hot showers, remain hydrated, use alcohol, dye- fragrance free products
27
Q

Regorafenib
1. targets
2. DDI’s ?
3. FDA approval for

  1. Dosing ?
  2. BBW for ?
  3. AE’s ?
A
  1. VEGFR, PDGFR, C-KIT, REF, BRAF
  2. CYP3a4 substrate
  3. metastatic CRC , in pt’s who have received a fluoropyrimidine-oxaliplatin, irinotecan and VEGF inhibitor tx
  4. 160 mg PO qam with a low fat meal
  5. Hepatotoxicty !!!!
  6. Fatigue
    * Decreased appetite
    * Hand-foot skin reaction
    * Diarrhea
    * Mucositis
    * Infection
    * Hypertension
28
Q

Ivosidenib –> IDH1

  1. Used in which state?
  2. Dose
  3. BBW? whats the onset ?
  4. AE’s
  5. DDI’s?
A
  1. relapsed or refractory AML w/susceptible IDH1 mutation
  2. 500 mg PO daily w/or without food until disease progression or unacceptable toxiicty –> avoid HIGH FAT meal
  3. Differentiation syndrome (fever, dyspnea, hypoxia, pulmonary infiltrates,
    pleural or pericardial effusions, rapid weight gain or peripheral edema,
    hypotension, and hepatic, renal, or multi-organ dysfunction)
    -7-10 days to 5 months after initiation
  4. Fatigue, arthralgia, leukocytosis, mucositis, rash, cough, nausea, diarrhea, constipation
  5. CYP3A4 inducers/inhibs and QTc prolonging drugs
29
Q

See chart for Drug Combo Lapatinib for Breast Cancer

A

See chart

Oncology Therapeutics (17 decks)

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