14.2 (12.2) Disease modifying therapies in advanced cancer

Question 1

List 3 factors that influence the stage of cancer at the time of diagnosis

(ie how early will cancer be diagnosed)

Answer 1

1. Resource factors such as:
   region where the patient is living (more advanced disease in developing countries)
   the health-care system
   screening programmes
2. patient factors such as:
   cancer awareness
   beliefs
   financial resources
3. cancer-related factors such as:
   visibility (ulcerations)
   early physical complaints (e.g. bleeding and pain)

Question 2

List THREE advanced cancers that can be cured with chemotherapy alone

Answer 2

◆ germ cell
◆ acute lymphoblastic leukaemias*
◆ Hodgkin’s disease*
◆ high-grade non-Hodgkin’s lymphoma*

Box 14.2.1

Question 3

List THREE advanced cancers that can be cured with combination of chemo + surgery*

Answer 3

◆ breast *
◆ lung*
◆ colorectal*
◆ osteosarcoma

Box 14.2.1

Question 4

List THREE advanced cancers that can be cured with a combination of chemo + rads*

Answer 4

◆ head and neck cancer*
◆ lung*
◆ anal *

◆ cervical

Box 14.2.1

Question 5

List 2 cancers where lymph node dissection will contribute to better overall survival even in advanced stage cancer

Answer 5

intermediate and high-risk endometrial cancer
malignant melanoma*
non-small cell lung cancer *
bladder cancer*

Question 6

Metastasectomy resulting in improved survival is possible for mets in what three organs

Answer 6

brain (in combo w/ whole brain rads)
Lung
Liver

Question 7

Radioisotopes are used to control advanced disease. Give two examples of cancers that utilize this therapy and list the isotope used

Answer 7

thyroid cancer - radioactive iodine (WP: ?iodine 131)

carcinoid tumors (met) - yttirum (90Y)-edotreotide

castration resistant prostate cancer - radium 223

WP: move to 14.3?

Question 8

List FOUR major categories of medications used to treat cancers (name ONE example of each)

Answer 8

◆ Hormone therapy (ADT and aromatase inhibitor)
- letrozole, tamoxifen

◆ Cytotoxic agents
- antimetabolites (5-FU, capecitabin)
- alkylating drugs (cyclophosphomide, ifosfamide)
- anti-tumor antibodies (doxorubicin, bleomycin)
- Plant alkaloids (vincristine, paclitaxel)

◆ Targeted agents
- monoclonal antibodies “-mabs” (bevacizumab, panitumumab)
- small molecules inhibiting protein kinase “-nibs” (imatinib, sorafenib)

◆ Immune system modulating drugs (aka checkpoint inhibitors)
- monoclonal antibodies “-mabs” (ipilimumab, nivolumab)

Question 9

List four cancers where hormone therapy plays a role (name the hormone therapy)

Answer 9

breast cancer - aromatase inhibitor
prostate cancer - ADT (androgen deprivation therapy)
thyroid cancer - synthroid 
neuroendocrine tumors - somatostatin analogues
endometrial cancer

Question 10

List FOUR side effects of hormone therapy (anti-estrogen) in breast cancer

Answer 10

hot flushes
sweats
osteoporosis
loss of sex drive
vaginal discharge
thromboembolism

FS:
Hot
Osteoporosis

Sex drive
Sex function (vag dryness, erectile dysfunction)

Fatigue
Depression

(HOSS-FD)

Question 11

List SIX side effects of hormone therapy (anti-androgen) in prostate cancer

Answer 11

absent sex drive
erectile dysfunction

Depression
Fatigue
Anemia

Loss of muscle
Osteoporosis

hot flushes

inc cholesterol

weight gain

dec mental sharpness

Question 12

Targeted therapy

• Name 2 broad types
• Name 2 examples of each type
• Name 2 molecular targets

Answer 12

◆ Monoclonal antibodies
- bevacizumab: vascular endothelial growth factor (VEGF)*
- cetuximab: endothelial growth factor receptor (EGFR)*
- panitumumab: EGFR
- trastuzumab: human epithelial growth factor receptor 2 (HER-2)
- pertuzumab: HER-2

◆ Small molecule protein kinase inhibitor (TKI)
- afatinib: EGFR
- erlotinib: EGFR*
- gefitinib: EGFR*
- lapatinib: EGFR, HER-2
- imatinib: BCR ABL, KIT, PDGF
- everolimus: mTOR
- temsirolimus: mTOR
- sorafenib: VEGF, KIT, PDGF, RET, RAF
- sunitinib: VEGF, KIT, PDGF, RET, FLT3

Table 14.2.2

FS: BEET
Bevacizumab
Erlotinib
Everolimus
Trastuzumab

Question 13

List FIVE immune-related adverse events (IRAE) associated with checkpoint inhibitors/immunotherapy

Answer 13

◆ hypophysitis
◆ throiditis
◆ mucositis
◆ vitiligo
◆ pneumonitis
◆ pancreatitis
◆ hepatitis
◆ nephritis
◆ neuropathy

Box 14.2.4

FS:
Thyroiditis
Pneumonitis
Hepatitis
Pancreatitis
Colonitis

Question 14

What are 2 side effects of EGFR modulators (TKI, monoclonal antibodies)

Answer 14

cardiotox w/ lapatinib (due to HER2 inhibition)

GI s/e

skin toxicity

Question 15

What are the THREE primary aims of anticancer treatment in advanced disease

Answer 15

◆ curative
◆ life prolongation
◆ symptom management

Question 16

Name SIX essential elements of the cancer phenotype.*

Answer 16

◆ proliferate in the absence of ext. growth factors
◆ lack of response to growth inhibitors

◆ avoidance of apoptosis
◆ unlimited replicative capacity

◆ overcoming immune system
◆ induction of inflamm

◆ angiogenesis

◆ met spread

Question 17

Define primary & secondary resistance to cytotoxic drugs

Answer 17

primary - cancer forms that are not responsive to cytotoxic drugs at the START of treatment

secondary - loss of effect DURING treatment due to selection of cancer cells that are not sensitive to cytotoxic drugs

Question 18

Name 4 patient-related factors associated with high risk morbidity & mortality in febrile neutropenia

Answer 18

◆ advanced dz*
◆ older age*
◆ malnutrition

◆ prev febrile neutropenia
◆ heavily pre-treated patients
◆ presence of cytopenias due to bone marrow involvement

◆ current infections
◆ liver/renal dysfunction*
◆ multiple comorbidities*