Oncology Flashcards Preview

4th Year Drugs > Oncology > Flashcards

Flashcards in Oncology Deck (77):
1

What is chemotherapy in general?

Group of cytotoxic agents used to SYSTEMATICALLY manage cancer

2

Why is it necessarily for chemo to systemically Tx patients, rather than being just localised?

Metastasis kills patients, not local recurrence in primary organ

3

What is the % of people with cancer who will require chemotherapy?

60-70%

4

What is the mechanism by which chemo exerts its anti-cancer action?

Most target DNA directly/indirectly

Preferentially toxic to actively proliferating cells ∴ work best on rapidly dividing tumours

5

What are the uses for chemo?

  • NEOADJUVANT - Tx of operable tumour pre-op to reduce its size ∴ allow for less radical Tx. Also Tx micro mets.
  • PRIMARY - initial Tx for inoperable tumour - reduce tumour bulk to allow surgical resection (↑ cure rates)
  • ADJUVANT - post op Tx for micro mets after complete resection (↑ cure rates)
  • PALLIATIVE - relieve Sx and prolong life when incurable. Balance so not to ↓ QoL
  • CURATIVE - mostly germ cell, (non)Hodgkin's lymphoma, childhood cancer WITHOUT surgery, even with mets! ∴ justifies intensive Tx with ↑ toxicity
  • PROPHYLACTIC - hormonal Tx before overt malignancy appears e.g. tamoxifen for in-situ breast cancer before invasive carcinoma

6

Cytotoxic chemo is most commonly given in combo of different drugs. Why is this?

  1. Different mechs of action give highest chance of result (several sub-lethal cell injuries can kill cell in combination- synergism) 
  2. ↓ chance of drug resistance
  3. Different drugs = different toxicity effects ∴ dose can be maintained

7

How are most schedules of chemotherapy treatments given? 

Cyclically - every 3-4 weeks

8

Why are chemotherapy treatments scheduled cyclically (i.e. every 3-4 weeks)?

Allows normal cells to recover from toxicity - low blood counts (myelosuppression) and mucositis 

Repeated cycles required for full clearance as only a proportion of tumour cells killed each time

 

9

Why are many chemotherapy treatments only maximally effective after a 6 month course?

Due to resistance emergence (chemo sensitive die and resistant remain ► replicate) and increased toxicity

10

Why do most people with cancer take conventional doses of chemotherapy?

Known to be effective against the particular malignancy in majority of PTs

Side effects are tolerable

11

Why is it bad to take high doses of chemo? 

Higher toxicity, and potentially lethal SEs (1-2% mortality) (bone marrow suppression) → specialised supportive care required (GFs, rescue stem cells/bone marrow, ABx)

12

What cancers are ones where high doses of chemo are justified? 

High doses justified only when long term survival or cure possible (HELL-MUG):

Hodgkins

Ewing's sarcoma

Leukaemia

Lymphoma

MUltiple myeloma

Germ cell tumours of testis

13

Why is prolonged chemotherapy to maintain remission not advised/advantageous?

Increased resistance and toxicitiy 

14

What condition/group of patients is maintenance chemotherapy advised? 

Childhood Leukaemia - 18 months maintenance Tx post remission

15

What is the advantage of giving chemo orally?

Freeing the patient from lenghty hospital visits and invasive procedures 

16

What is the disadvantages of taking chemo orally?

  1. Doesnt reduce toxicity - requires regular review
  2. Only few chemo drugs avaliable orally (cyclophosphamide, etoposide, capecitabine, tamoxifen)
  3. Absorption issues can effect levels in circulation 

 

17

How is most chemotherapy given?

IV mostly as bolus injection or short infusion.

Can be continuous infusion via central line 

18

Chemotherapy Tx can be administered regionally. What are the methods?

Intravesical - high doses given at site, ↓ systemic absorption and toxicity e.g. superficial bladder cancer 

Intraperitoneal  - for trans-coelomically spread tumour e.g. ovarian cancer

Intra-arterial - for tumours with well-defined blood supply (e.g. hepatic artery infusion for liver mets). ↑ doses to involved site ↓ systemic absorption

19

How are chemotherapy doses calculated?

Most calculated according to patients body surface area (DuBois and DuBois formula):

BSA = (Weight (kg) 0.425 x Height (cm) 0.725) x 0.007184 

Others:

  • Carboplatin - renal function
  • Newer drugs e.g.traztuzumab - body weight

20

What type of ADVANCED cancers is chemo most effective (i.e. cure of advanced disease in >50%)

Hodgkins disease

Testicular/germ cell cancers

Acute lymphoblastic leukaemia 

Choriocarcinoma 

Paediatric cancers e.g. leukaemia, lymphoma, sarcoma

21

What are the ADVANCED cancers where chemo is less effective (<50% cure)

Non-Hodgkins

Ovarian cancer

Paediatric Neuroblastoma

Osteosarcoma, Ewings Sarcoma, Rhabdomyosarcomas

22

What types of REGIONAL cancers will chemo increase cure rates?

Breast

Colorectal

Non-small cell Lung

Oesophageal/gastric

Bladder

23

What types of cancer will chemo result in remission in most pts?

Those in list of curable cancers.

Breast

Small cell lung cancer (very chemo sensitive)

Ovarian cancer

24

What types of ADVANCED REGIONAL cancer will chemo prolong survival but NOT cure in most?

Non-small/small cell lung cancer

Colorectal cancer

Gastric cancer

Breast cancer 

Bladder

Prostate

25

What types of cancer is chemo only really effective for pallitation of Sx?

Renal Cancer

Melanoma

Head and neck cancer

Pancreatic

Billiary Tract cancers 

26

What are the IMMEDIATE GI SEs of chemotherapy 

N&V - direct stimulation of vomiting centre, peripheral stiumlation and anticipatory.

GI - rapidly dividing cells ∴ susceptible. 

  • Mucositis (especially oral)
  • Diarrhoea (colitis/inflammation)
  • Constipation  (dehydration, other drugs e.g. opioids)

27

What are the IMMEDIATE bone marrow related SEs of chemotherapy?

Myelosuppression - kills haematopoietic progenitor cells.

  • ↓WCC (< 1 x 109), ↓platelets  (rare if standard doses used) - after 10-14 days.
    • Higher doses - cause worse/longer leucocyte fall (but drug dependent)
    • Lowest point of drop = nadir.
    • Recovery after 3-4 weeks.

28

What are the immediate hair related SEs of Chemo?

Alopecia - hair follicles rapidly dividing (reversed with discontinuation) - ↓ with cold cap 

29

What are the immediate neurological SEs of chemotherapy?

  • Peripheral/Autonomic neuropathies (mainly sensory)  (e.g. cisplatin, taxanes, vinca alkaloids)
  • Central toxicity - ifosfamide induced encephalopathy, 5-FU induced cerebellar toxicity
  • Ototoxicity (e.g. pernament cochlear damage with cisplatin) 

30

What are the immediate genitourinary SEs of chemotherapy?

  • Nephrotoxicity - e.g. cisplatin, ifosfamide - renally excreted ∴ adequate renal func required
  • Bladder toxicities e.g. cyclophosphamide, ifosfamide - haemorrhagic cystitis

31

What are the immediate cardiac SEs of chemotherapy? 

  • Arrythmias e.g. doxorubicin, paclitaxel 
  • Cardiac ischamia (coronary art spasm) - 5-FU

32

What are the immediate hepatic SEs of chemotherapy?

  • ↑LFTs (transient)
  • Failure (rare)

33

What are the immediate skin and soft tissue SEs of chemotherapy?

  • Extraversion (leakage of IV drugs) - some chemo = highly vesicant and can cause dmg ∴adminsiter through fast running drips, use dilutants and withdraw if EV occurs
  • Palmar plantar erythema (Hand foot syndrome) - temporary
    •  5FU, caecitabine, some targetted agents.
    • Cause unknown.
    • Tx with emollients. 
  • Photosensitivity - 5FU, use high factor sunscreen 
  • Skin/nail Pigmentation - beau lines -  bleomycin (+ pilmonary fibrosis)
     

34

What are the 'other' immediate SEs of chemotherapy?

  • Myalgia and arthralgia - paclitaxel (Tx with NSAIDs)
  • Allergic reactions - paclitaxel and docetaxel ass with hypersensitivity 
  • **Lethargy** - general malaise = common and debilitating. Unknown aetiology

 

35

What are the long term complications with chemotherapy? 

  • Secondary malignancies - e.g. alkylating agents/procarbazine
    • Sub -lethal DNA dmg  → genetic changes → 2o malignancy
  • Fertility e.g. alkylating agents, high dose
    • consider sperm/ova storage 
  • Pulmonary fibrosis/pneumonitis 
    • e.g. bleomycin, busulphan, alkylating agents - particularly high dose/prolonged
  • Cardiac fibrosis e.g. docorubicin 
  • Psychological and social - ↓QoL

36

What is the Tx of anaemia?

  • Hb <10gdl - impair quality of life 
    • Transfusion
    • Recombinant EPO - ↓risk of transfusion reaction/viral transmission

37

What are the signs of thrombocytopenia?

  • Petechial haemorrhage
  • Nose bleeds
  • Corneal haemorrhage 
  • Haematuria 

38

What is the Tx for thrombocytopenia?

  • Ass with high dose chemotherapy (as opposed to standard doses)

Tx dep on platelet count

  • <10 x 109 - Urgent platelet transfusion 
    • sig risk of spontaneous bleeding e.g. intra-cerebral 
  • ​10 x 109 - 20 x 109 - supportive platelet tranfusion 
  • >20 x 10- do not need platelet trans routinely 

 

39

What are the potential SEs of repeated administration of blood products?

  • Development of specific anti-bodies to blood cells 
    • failure to ↑platelet counts immediately after transfusion
    • Reduce development with using single donor donations

40

What are three main types of targetted agent therapies?

  1. MONOCLONAL ANTIBODIES (end in -mab) - IV infused
    • Trastuzumab (Herceptin) - HER2 receptor
    • Ipilimumab  
  2. TYROSINE KINASE INHIBITORS (end in -ib) - Oral​ 
    • Erlotinib - anti EGFR for NSCLC
    • sunitinib - anti-VEGFR (palliative for renal cell, pancreatic, GI stromal)
    • Vemurafenib - metastatic melanoma 
    • Metabolised by CYP450 - remember drug interactions
  3. mTor INHIBITORS (end in -us) - oral (Everolimus) or IV (temsirolimus)
  • Serine/threonine kinase inhibitor of mTor, part of the apoptosis pathway.
  • Palliative in renal cell and in mets breast cancer ER+HER2+.

41

What are the SEs the targetted chemo therapies? 

    Theoretically better than normal chemotherapy
    • More toxic to cancer
    • Less damage to normal cells
    • Better tolerated - long periods with fewer breaks (chronic dosing)
  • However, chronic dosing can lead to:
    • Chronic toxicity - low grade Sx e.g. mild diarrhoea, taste change, rash 
      • tolerable for few weeks but can adversely affect QoL long term
    • Emergent toxicity - only apparent after months of Tx e.g. thyroid disturbance with sunitinib
    • Risk of drug interaction 
    • Mounting costs

42

What type of cancers are hormonal therapies useful in?

Only work in cancers which are 'hormone dependent'  i.e.  cancers arising from tissues under hormonal control 

  • Prostate
  • Breast
  • Endometrium
  • Lymphocytic e.g. lymphoma, leukaemia, myeloma

43

At what stages are hormone treatments useful in cancer treatment?

  • Shrink 1o tumours before (NEOADJUVANT) OR instead of sugery (1o medical therapy)
  • Prevent/delay growth of micromets following surgery (ADJUVANT)
  • Shrink estalbished mets and improve QoL/prolong survival (PALLIATIVE)

44

Regarding hormone therapies, what techniques are employed to remove SOURCES of hormone production?

 

  • Surgically e.g. oophorectomy, bilateral orchidectomy
  • Radiotherapy induced ablation
  • Reversible Medical castration 

45

What are the reversible medical castration methods that are used? Name examples for both

LHRH/GnRH blockers e.g. goserelin (zoladex), leuprorelin, degarelix (♂)

  • Block LH/FSH production by pituritary gland (indirectly/directly)  (non-menopausal ♀/♂) 
  • ∴ ↓ gonadal hormone production
  • Not for post-menopausal ♀ ► oestrogen = extra-gonadal (fat/adrenals)

AROMOTASE INHIBITORs  e.g. anastrozole, exemestane, letrozole

  • Post-menopausal ♀
  • Blocks aromatase - converts androstenedione to oestrone
  • ↓ oestrogen synthesis from androgens

46

How do aromotase inhibitors work?

  • Blocks Aromotase - Enzyme which aromatases androstenedione (from adrenals) to oestrone (oestrogen synthesis)

 

47

Why did older versions of aromatase inhibitors require co-prescribed corticosteroids?

  • Earlier ones (e.g. aminoglutethimide) used to block earlier stages of steroid synthesis  ∴ required corticosteroid supplements. 
  • Newer inhibitors e.g. anastrozole, exemestane, letrozole = more specific blockage

48

Regarding hormone therapies, what methods are used to inhibit hormones?

  • Block hormone binding in tumour cell receptors

    • Anti-oestrogen - blocks oestrogen receptors e.g. Tamoxifen (breast cancer) 

    • Anti-androgen - blocks androgen receptor (tumour and hypothalamus)  e.g. Flutamide, bicalutamide, cyproterone acetate 

49

What are the side effects of using LHRH/GnRH blockers and hormone blockers?

  • Rapid increase in gonadotrophins ('FLARE') (7-10 days)
    •  Can worsen Sx short term e.g. bone pain 
  • Non specific Sx
    • Fatigue 
    • Impotence
    • Hot flushes/Sweating
    • Menopausal Sx - vaginal dryness, hot flushes, sweating, ↓labido
    • Breast tenderness/gynaecomastia
    • Hair thinning (♀)
    • Mood changes 
    • ↓Memory
    • Oesteoperosis (↓testosterone/oestrogen)
    • ↑weight ∴ ↑cardiac risk
    • Thrombosis (♀) - esp tamoxifen 

50

How could you increase the response of hormone therapy in different cancers?

Combination hormone therapy 

  • Some can produce improved response rates (LHRH blockers + hormone blockers)
  • However, can ↑SEs without increasing efficacy

51

Regarding hormone therapies, what methods are used to increase hormones? (i.e. tumour growth reducing)

  • Glucocorticoids - induce apoptosis in malignant lymphoid cells
    • e.g. lymphoid leukaemia, lymphoma, myeloma, Hodgkin's
  • Sex-hormones to induce -ve feedback loops
    • oestrogen - down-regulate LRHR in prostate cancer
  • Progestogens e.g. medroxyprogesterone acetate
    • ​progesterone sensitive tissues (breast, endometrium)
    •  ↓tumour growth by inhibiting progesterone receptor and  inducing -ve feedback loops

52

What is radiotherapy? 

  • Use of ionising radiation for managing loco-regional cance

53

What is the mechanism by which RT works?

  • X-rays penetrate body tissue whilst sparing overlying skin
  • Produce electrons/free radicals that damage DNA in cancers/normal cells
    • Normal cells - repair DNA damage and ∴ survive ('skin sparing')
    • Cancer cells - defective DNA repair ∴ mitotic/apoptotic cell death 

54

At what stages in cancer can radiotherapy be used?

  • Radical/curative - if no METs,  may be delivered as sole Tx modality (e.g. prostate cancer) or in combo with chemo
  • Neo-adjuvant  - reduce risk of local recurrence e.g. rectal ca
  • Adjuvant - reduce local-regional recurrence e.g. breast Ca
  • Palliative - ↓Sx/↓growth

55

What ways is radiotherapy delivered?

Delivered by LINEAR ACCELERATOR in form of:

  • Photons/X-rays (External beam)**
  • Electrons
  • Radio-isotopes
  • Protons 

** most common in UK

56

What units are used to express doses of radiation delivered to body tissues?

Gray (Gy) 

57

How is radiotherapy delivered (doses)?

  • Series of small doses (fractions) rather than one large dose
  • Number of fractions and dose (Gy) depends on Tx intent

58

If the intent of RT is curative, what dose/number of fractions would you expect?

  • Large dose overall over multiple small fractions
    • e.g. head/neck - 70Gy in 35 fractions over 7 weeks

59

If the intent of RT is palliative, what dose/number of fractions would you expect?

  • Alleviate Sx - small number of fractions and lower doses
  • e.g. 8Gy in 1 fraction, 20Gy in 5 fractions, 30Gy in 10 fractions

60

 Regarding tumour kill and toxicity of RT, what factors can influence the degree of these?

  • Treatment issues e.g. Tx dose, total volume Tx, doses per fraction, Tx time
  • Co-morbidities e.g. DM, IBD, smoking
  • Cancer radiosensitivity 
    • HIGHLY SENSITIVE - Germ cells, Lymphocytes e.g. Hodgkins  
    • MODERATE SENSITIVIE - Epithelial cells
    • HIGHLY RESISTANT -  CNS cells (e.g. glioblastoma multiform), Connective Tissue cells
  • Tumour hypoxia - hypoxic cells 2-3x less sensitive

  • Additional treatments (concurrent chemo increases radio sensitivity but also increased toxicity) 

61

What is the term used to describe the balance between tumour control and SEs of Tx?

Therapeutic index

62

What is the most common external beam radiotherpy used? What is the process? 

  •  3D conformal radiotherapy - individual tumour mapping to target tumour 
    • tumour shape and size measured with CT
    • Patient immboilised 

63

64

When measuring CT slices for radiotherapy, what volume do you get? 

Gross tumour volume (GTV)

65

Regarding RT, what margin is used to account for potential microscopic spread?

Clinical target volume (CTV)

66

Regarding RT targetting, what margin is used to account for minor daily variations in patient/tumour position? 

Planning target volume (PTV) 

 

67

Why is a RT plan created? (i.e. RT accounting for gross tumour, clinical target and planning target volumes)

Allow specific targeting and reduce damage to normal tissue.  

68

How is the target of RT defined? (GTV, CTV, PTV)

69

What are the instant SEs of RT?

  • Teratogenic - CI in pregnancy
  • Painless during delivery 

70

What are the acute SEs of Radiotherapy?

  • Localised Tx ∴ SEs related to anatomical areas of body receiving Tx. Usually after first 5-10 fractions. SEs ↑ during Tx and peak in first few weeks 
    • Due to damage of normal tissue (reversible)

REMEMBER - SHORT TERM = INFLAMMATION (-itis)

  • Fatigue/weakness
  • Skin - Erythema ► desquamation (peeling, moist, pain) ► ulceration 
  • Oral - erythema, ulceration
  • Mucositis/Oesphagitis 
  • Gastrititis/colitis- N&V/Diarrhoea
  • Rectum - tenesmus, mucous discharge, bleeding
  • Pneumonitis - cough, dyspnoea, X-ray changes
  • Pericarditis 

71

What are the long term side effects of RT?

  • >3 months after RT (can manifest yrs after) - often irreversible, worsen with time, difficult to manage

REMEMBER - LONG TERM SE = BROADLY FIBROSIS (-osis)

  • Skin - skin colour change, atrophy, fibrosis, telangiectasia,
  • Oral Mucosa - Dry mouth (salivary gland irridation)
  • GI - mucosal ulceration, fibrosis/obstruction, necrosis 
  • CNS - demyelination effects 
  • Lung - fibrosis 
  • Heart -  cardiomyopathy/conduction blocks 
  • Infertility/↓labido/impotence
  • Carcinogenic - (2cancer 5-30yrs after exposure) - esp thyroid/breast (e.g. mantle RT) and in childhood/young adulthood

72

73

74

What is brachytherapy? What is it used for? 

  • Radiation Tx where radiation sources = placed within/close to tumour 
    • ↑tumour dose and ↓dose to surrounding tissue
  • Prostate, gynaecological, oesphageal, neck cancers

75

What are the two types of brachytherapy?

  1. Intracavity - radioactive material placed INSIDE body cavity e.g. uterus, cervix
  2. Interstitial - material put into target e.g. prostate 

76

What is the problem of brachytherapy?

  • Patient will be RADIOACTIVE 
    • advise patient about radiation risk to others 

77

What cancer uses radioisotopes in its therapy? What does it entail and what are the associated risks?

  • Radioisotopes - unstable chemical element - emits radiation when it decays 
    • Thyroid - iodine I-131
      • Specifically taken up and concentrated by thyroid tissue 
      • Emits radiation as it undergoes radioactive decay
  • Patient = irradiated and risk to others 
    • ∴ must remain in lead room until radiation is low so not to pose a risk to others (~4 days)