Medical Oncology Flashcards
What malignancy and manifestations is antibody Hu associated with?
Small cell lung cancer
Limbic encephalitis, peripheral neuropathy
What malignancy and manifestations is antibody Yo associated with?
Breast / Ovarian Ca
Cerebellar degeneration
What malignancy and manifestations is antibody Ri associated with?
Small cell lung cancer
Opsoclonus myoclonus, rhomboencephalitis
What malignancy and manifestations is antibody Ma/Ta associated with?
Testicular cancer
Rhomboencephalitis
Which malignancies is H Pylori associated with?
Gastric cancer
MALT lymphoma
Mechanism is chronic inflammation
Which cancers is HPV implicated in?
Cervical cancer
Vulval cancer
Vaginal cancer
Penile cancer
Anal cancer
Oropharyngeal cancer
Which genes are involved in the pathogenesis of Lynch syndrome?
MLH1
MSH2
MSH6
PMS2
EPCAM
MLH1 and PMS2 co-associated
MSH2 and MSH6 co-associated
Name 5 different classes of chemotherapy.
Alkylating agents - e.g. platinum-based, mustard-based
Anti-metabolites - anti-folates, purine and pyramidine analogues
Alkaloids - microtubule and topoisomerase poisons
Antibiotics
Hormones
Name 6 different alkylating agents.
Mustard and derivatives
- cyclosporin
- cyclophosphamide
- chlorambucil
- temozolamide
Platinum agents
- cisplatin
- carboplatin
- oxaliplatin
What is the mechanism of action of alkylating chemotherapy agents?
Non-cell cycle specific
“Alkylates” guanine, distorting DNA structure; repair enzymes fail and fragment DNA
Cross-links DNA forming strong bond preventing helicase separating double strand, preventing replication
Name 5 examples of anti-metabolite chemotherapy.
Purine antagonists (adenine, guanine)
- fludarabine
- 6MP
- methotrexate
Pyramidine antagonists (thymine, cytosine, uracil)
- 5FU
- gemcitabine
Name 6 different alkylating agents.
Mustard and derivatives
- cyclosporin
- cyclophosphamide
- chlorambucil
- temozolamide
Platinum agents
- cisplatin
- carboplatin
- oxaliplatin
Name 5 different classes of chemotherapy.
Alkylating agents - e.g. platinum-based, mustard-based
Anti-metabolites - anti-folates, purine and pyramidine analogues
Alkaloids - microtubule and topoisomerase poisons
Antibiotics
Hormones
Name 5 examples of anti-metabolite chemotherapy.
Purine antagonists (adenine, guanine)
- fludarabine
- 6MP
- methotrexate
Pyramidine antagonists (thymine, cytosine, uracil)
- 5FU
- gemcitabine
How do alkaloids work?
Vinca alkaloids - bind to tubulin and stop microtubule formation
Taxanes - bind to tubulin and stop microtubule disassembly
Topoisomerase inhibitor - DNA “tensioning” - S phase specific
Name 7 examples of alkaloids.
Vinca alkaloids
- vincristine
- vinblastine
- vinorelbine
Taxanes
- paclitaxel
- docetaxel
Topoisomerase inhibitors
- Irinotecan
- etoposide
Name 5 examples of antibiotic-based chemotherapies.
Doxorubicin
Daunorubicin
Epirubicin
Mitoxantrone
These are anthracyclines derived from streptomyces bacteria
How do alkaloids work?
Vinca alkaloids - bind to tubulin and stop microtubule formation
Taxanes - bind to tubulin and stop microtubule disassembly
Topoisomerase inhibitor - DNA “tensioning” - S phase specific
Name 7 examples of alkaloids.
Vinca alkaloids
- vincristine
- vinblastine
- vinorelbine
Taxanes
- paclitaxel
- docetaxel
Topoisomerase inhibitors
- Irinotecan
- etoposide
Name 5 examples of antibiotic-based chemotherapies.
Doxorubicin
Daunorubicin
Epirubicin
Mitoxantrone
These are anthracyclines derived from streptomyces bacteria; non-cell cycle specific; interferes with topoisomerase 2
How do anthracycline chemotherapies work?
Interferes with topoisomerase 2
Metabolite is a free radical causing widespread damage
Non-cell cycle specific
Induces histone eviction from chromatin
…definitely not to treat infections
Name 6 classes of hormone-based chemotherapy.
LHRH analogues e.g. lucrin, Zoladex
Selective Oestrogen Receptor Modulator (SERM) e.g. tamoxifen
Aromatase inhibitors e.g. anastrozole, letrozole
Steroidal aromatase inhibitors e.g. exemestane
Peripheral androgen blockers e.g. bicalutamide, glutamine
Adrenal androgen synthesis e.g. abiraterone
How does obesity impact upon the chance of developing pre-menopausal and post-menopausal breast cancer?
Obesity decreases the chance of developing pre-menopausal breast cancer
Obesity increases the chance of develop post-menopausal breast cancer
Which gene is deleted in Familial Adenomatous Polyposis?
Deleted APC gene as germ-like mutation
25% have no family history
Which cancers may be seen in conjunction with FAP besides colorectal cancer?
Papillary thyroid
Ileal carcinoid
Gastric cancer
What is the Amsterdam criteria for Lynch syndrome?
“3-2-1 rule”
3 affected members
2 generations
1 under age 50
What features would suggest that a stage 2 colorectal cancer might be “high risk”? Name 4.
Obstruction
Poor differentiation
Extramural venous invasion
Adjacent organ invasion
What is the treatment for stage 2colorectal cancer?
Surgery cures 80% of cases
3-6 months adjuvant chemo for high risk stage 2 (5FU)
Which cancers may be seen in conjunction with FAP besides colorectal cancer?
Papillary thyroid
Ileal carcinoid
Gastric cancer
What is the Amsterdam criteria for Lynch syndrome?
“3-2-1 rule”
3 affected members
2 generations
1 under age 50
What features would suggest that a stage 2 colorectal cancer might be “high risk”? Name 4.
Obstruction
Poor differentiation
Extramural venous invasion
Adjacent organ invasion
What is the treatment for colorectal cancer?
Surgery
3-6 months adjuvant chemo for high risk stage 2 and stage 3
What is the treatment for colorectal cancer?
Surgery
3-6 months adjuvant chemo for high risk stage 2 and stage 3
What is the treatment for stage 3 colorectal cancer?
Stage 3, any T, N1/2 - surgery + 6 months adjuvant FOLFOX
T3/4 or node positive disease in rectal - XRT too (5FU is sensitiser)
If resectable mets - aim to cure
If unresectable - chemo (FOLFOX/FOLFIRI) + targeted therapy
What is bevacizumab, how does it work and what adverse effects does it have?
Mono Ab - binds and inhibits VEGF
Hypertension
Proteinuria
GI perforation
Thromboembolic events
Delayed wound healing
Can be used regardless of RAS/RAF status and location of tumour
What is bevacizumab, how does it work and what adverse effects does it have?
Mono Ab - binds and inhibits VEGF
Hypertension
Proteinuria
GI perforation
Thromboembolic events
Delayed wound healing
Can be used regardless of RAS/RAF status and location of tumour
What is cetuximab, how does it work and what are its side effects?
Mono Ab - anti-EGFR (EGFR -> RAS -> RAF -> MAPK)
Indicated in KRAS/RAF wild type (50% of CRC)
Rash (correlates with activity)
Skin sensitivity
Diarrhoea
Renal salt wasting
Worse toxicity in combination with capecitabine
What is cetuximab, how does it work and what are its side effects?
Mono Ab - anti-EGFR (EGFR -> RAS -> RAF -> MAPK)
Indicated in KRAS/RAF wild type (50% of CRC)
Rash (correlates with activity)
Skin sensitivity
Diarrhoea
Renal salt wasting
Worse toxicity in combination with capecitabine
What is trifluridine/tiperacil (Lonsurf)?
Nucleoside analogue and thymidine phosphorylase inhibitor
Works differently to 5-FU based fluoropyrimidines for CRC
SE - neutropenia
With GIST, what positive maker would you expect to see?
CD117 positive in 50% of cases (C-kit positive)
What sort of cells do you expect to see with GIST on histopath?
Spindle shaped cells
How are GISTs treated?
Imatinib
If PD - escalate doses (800mg daily max), then sunitinib and regorafenib
As well as a hypervascular liver lesion, what sort of AFP level would you expect to see in patients you suspect of HCC?
AFP >400
What is the main cause of HCC in Australia?
Viral hepatitis infection
What is the Barcelona Criteria for HCC and how does it influence treatment?
Stage 0 - single <2cm lesion, carcinoma in situ - resect/transplant
Stage A-B (multiple nodules, CPA or B) - chemoembolisation
Stage C - advanced(portal invasion) - TKIs
Stage D - terminal - (mets) - symptomatic
How is prostate Ca treated?
Organ confined - radical prostatectomy comparable to radical radiotherapy
Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy
What is the Barcelona Criteria for HCC and how does it influence treatment?
Stage 0 - single <2cm lesion, carcinoma in situ - resect/transplant
Stage A-B (multiple nodules, CPA or B) - chemoembolisation
Stage C - advanced(portal invasion) - TKIs
Stage D - terminal - (mets) - symptomatic
What is the main cause of HCC in Australia?
Viral hepatitis infection
As well as a hypervascular liver lesion, what sort of AFP level would you expect to see in patients you suspect of HCC?
AFP >400
How are GISTs treated?
Imatinib
If PD - escalate doses (800mg daily max), then sunitinib and regorafenib
What sort of cells do you expect to see with GIST on histopath?
Spindle shaped cells
With GIST, what positive maker would you expect to see?
CD117 positive in 50% of cases (C-kit positive)
How is prostate Ca treated?
Organ confined - radical prostatectomy comparable to radical radiotherapy
Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy
How is prostate Ca treated?
Organ confined - radical prostatectomy comparable to radical radiotherapy
Neo-adjuvant and adjuvant hormones for higher risk tumours treated with radiotherapy
In castrate-sensitive metastatic prostate cancer, patients with which symptoms benefit most from anti-androgen cover? Name 3 symptoms.
Extensive vertebral metastases
Risk of urinary retention
Poorly controlled pain
What is the treatment for metastatic castrate-resistant prostate cancer?
Chemo - docetaxel, cabazetaxel
Novel androgen receptor targeted therapies - abiraterone, enzalutamide
PARP inhibitors
Radiopharmaceuticals - radium-223, lutetium-PSMA
What is the treatment for metastatic castrate-resistant prostate cancer?
Chemo - docetaxel, cabazetaxel
Novel androgen receptor targeted therapies - abiraterone, enzalutamide
PARP inhibitors
Radiopharmaceuticals - radium-223, lutetium-PSMA
What are important toxicities with docetaxel? Name 3.
Sensory/motor PN
Neutropenic sepsis
Hypersensitivity reactions
What are important toxicities to consider with cabazitaxel? Name 4.
Diarrhoea
Cytopenias
Sensory/motor PN (less than docetaxel)
What are important toxicities to consider with abiraterone? Name 4.
Hypertension
Hypokalaemia
Peripheral oedema
Transaminitis
What are important toxicities to consider with enzalutamide? Name 3.
Hypertension
Fatigue
Contraindicated in seizures
What is sipuleucel T, and how is it used?
Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient
Used for metastatic castrate-resistant prostate cancer
Side effects are typically immune-based
What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.
Osteoporosis
Dyslipidaemia
Weight gain
BMD
Mood
Insulin resistance
CVS morbidity / mortality
What is the significant side effect of V600E inhibitors such as vemurafenib?
Hand-foot syndrome
How do the presence of brain mets impact upon melanoma treatment?
1-3 mets - stereotactic surgery (SRS) or surgery
> 3 mets - BRAF inhibitors or immunotherapy
Name 6 indications for BRCA testing in breast Ca.
<40 years old
“Triple negative” pathology <50 years
Bilateral breast Ca, one <50 years
Male breast cancer
Jewish ancestry
Family history of ovarian cancer
Name 3 indications for BRCA testing in ovarian Ca.
<70 years
Jewish ancestry
Family history of breast or ovarian cancer
What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.
Breast
- offer bilateral mastectomy (best age <40)
- offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
- offer screening - annual MRI/MG from age 30 (MG only from 50)
Ovarian
- RRSO once family complete or <35 (BRCA1), <45 (BRCA2)
No evidence for screening benefit
How do PARP inhibitors work?
Cell death via synthetic lethality
PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.
What are side effects of PARP inhibitors? Name 4.
Nausea
Diarrhoea
Fatigue
Abdominal pain
How does sentinel node biopsy help inform treatment plans for breast Ca?
Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required
1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast
> 2 sentinel nodes - axillary dissection improves local control
What chemotherapy agents are typically used for breast cancer?
Anthracycline (doxorubicin, epirubicin) best in meta-analyses
Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone
2 weekly dose dense chemotherapy better than 3 weekly
Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year
How does alcohol impact upon chemotherapy-induced emesis?
High ETOH is protective
For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?
RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone
RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment
RS >25 - chemo + hormonal therapy
What are side effects of tamoxifen? Name 2.
Increased DVT/PE
Increased risk of uterine cancer
Describe the interaction between SSRIs and tamoxifen.
Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine
Name 3 side effects of aromatase inhibitors.
Menopausal symptoms
Arthralgia
Accelerated osteoporosis
How does fulvestrant work, for whom is it indicated, and what is the major side effect?
ER destroyer
For metastatic breast Ca in post-menopausal women
Hepatoxicity
What are palbociclib/ribociclib, when can they be used and what is the major side effect?
CDK4/6 inhibitor
Metastatic breast Ca in combination with aromatase inhibitor or fulvestrant
Neutropaenia
What is everolimus, and when can it be used in breast Ca?
mTOR inhibitor
Metastatic breast Ca combined with exemestane
Name 3 side effects associated with everolimus
Stomatitis
Rash
Fatigue
Name 4 different HER2/3 target drugs.
Trastuzumab - HER2
Pertuzumab - targets HER2 and HER3 hetero-dimerisation
Lapatinib - oral anti-HER2 agent
T-DM1 - antibody drug conjugate
Which tumour markers are associated with seminomas and non-seminomas respectively?
Seminomas - bHCG (half-life 5-7 days)
Non-seminomas - AFP (half-life 18-36 hours)
AFP is NEVER seminoma
Name 4 risk factors for testicular cancer.
Siblings with testicular Ca (6-10x risk)
Crypto-orchidism
Klinefelter’s
Atrophy
What is the treatment for stage I (confined to testicle) seminomas following orchidectomy?
Option 1 - surveillance
Option 2 - 1 x carboplatin
What is the treatment for stage 1 (confined to testicle) non-seminoma?
Option 1 - surveillance
Option 2 - 1 x BEP
What is the standard chemotherapy regimen for metastatic testicular cancer?
BEP (bleomycin, etoposide, cisplatin) for 3-4 cycles
Surgical resection of residual disease in non-seminomas
Name 3 side effects associated with cisplatin.
Ototoxicity - dose-related, tinnitus; permanent high frequency hearing loss
Nephrotoxicity - average 15% decline in GFR in testicular patients treated with BEP
Neurotoxicity - peripheral (sensory) neuropathy, usually resolves in 6-12 months (may be permanent)
What types of chemotherapies are more likely to predispose patients to secondary malignancies?
Alkylating agents e.g. cyclophosphamide
What material predisposes to the development of mesotheliomas?
Blue asbestos (crocidolite)
What treatments are available for mesotheliomas?
Palliative chemotherapy with cisplatin and pemetrexed
Chemo toxicity can be reduced by concurrent treatment with B12 and folic acid
Some ICI activity in mesothelioma second-line
How are NSCLCs treated per stage in general terms?
Stage I and II
- surgery where patient is fit (radical, or SABR if not fit for surgery)
- adjuvant chemotherapy for resected stage II (hilar nodes involved)
Stage IIIA (ipsilateral mediastinal nodes involved) - radical combination radiotherapy + chemotherapy +/- surgery
Stage IIIB (contralateral mediastinal nodes involved) - palliative chemotherapy and/or radiotherapy
Stage IV (metastatic) - palliative chemotherapy and/or radiotherapy
What cancer would cancer cells staining for TTF1 suggest?
Adenocarcinoma
Name 3 factors that might suggest an EGFR mutation in an adenocarcinoma.
Female
Asian
Non-smoker
What sort of chemotherapies can be considered for palliative NSCLC?
Platinum drug + paclitaxel or gemcitabine or vinorelbine
Adenocarcinomas may do better with pemetrexed combined with platinum
In all lung cancers, name 2 factors where PD-L1 expression might be higher.
Males
Smokers
Name 4 targets for targeted therapies in lung adenocarcinomas.
EGFR mutation
ALK translocation
ROS1 re-arrangement
BRAF mutation
Name 3 drugs that can be used as targeted therapies in patients with lung adenocarcinoma with an EGFR mutation.
Erlotinib
Gefitinib
Afatinib
Name 2 drugs that can be used in lung adenocarcinoma with an ALK translocation.
Crizotinib
Alectinib
Alectinib has a better response rate (including CNS mets) and disease control at 12 months with lower toxicity than crizotinib
Name a drug that can be used in lung adenocarcinoma patients with ROS1 rearrangement.
Crizotinib
Name a drug combination that can be used in lung adenocarcinoma patients with a BRAF mutation.
Trametinib/dabrafenib
What are the 6 grades of ECOG?
0 - fully active, able to carry on all predispose activities without restriction
1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g. light housework or office work)
2 - Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours
3 - Capable of only limited self-care; confined to bed or chair more than 50% of waking hours
4 - Completely disabled and not capable of self-care; totally confined to bed or chair
5 - Dead
What is sipuleucel T, and how is it used?
Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient
Used for metastatic castrate-resistant prostate cancer
Side effects are typically immune-based
What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.
Osteoporosis
Dyslipidaemia
Weight gain
BMD
Mood
Insulin resistance
CVS morbidity / mortality
What is the significant side effect of V600E inhibitors such as vemurafenib?
Hand-foot syndrome
How do the presence of brain mets impact upon melanoma treatment?
1-3 mets - stereotactic surgery (SRS) or surgery
> 3 mets - BRAF inhibitors or immunotherapy
Name 6 indications for BRCA testing in breast Ca.
<40 years old
“Triple negative” pathology <50 years
Bilateral breast Ca, one <50 years
Male breast cancer
Jewish ancestry
Family history of ovarian cancer
Name 3 indications for BRCA testing in ovarian Ca.
<70 years
Jewish ancestry
Family history of breast or ovarian cancer
What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.
Breast
- offer bilateral mastectomy (best age <40)
- offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
- offer screening - annual MRI/MG from age 30 (MG only from 50)
Ovarian
- RRSO once family complete or <35 (BRCA1), <45 (BRCA2)
No evidence for screening benefit
How do PARP inhibitors work?
Cell death via synthetic lethality
PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.
What are side effects of PARP inhibitors? Name 4.
Nausea
Diarrhoea
Fatigue
Abdominal pain
How does sentinel node biopsy help inform treatment plans for breast Ca?
Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required
1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast
> 2 sentinel nodes - axillary dissection improves local control
What chemotherapy agents are typically used for breast cancer?
Anthracycline (doxorubicin, epirubicin) best in meta-analyses
Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone
2 weekly dose dense chemotherapy better than 3 weekly
Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year
How does alcohol impact upon chemotherapy-induced emesis?
High ETOH is protective
For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?
RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone
RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment
RS >25 - chemo + hormonal therapy
What are side effects of tamoxifen? Name 2.
Increased DVT/PE
Increased risk of uterine cancer
Describe the interaction between SSRIs and tamoxifen.
Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine
Name 3 side effects of aromatase inhibitors.
Menopausal symptoms
Arthralgia
Accelerated osteoporosis
What is sipuleucel T, and how is it used?
Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient
Used for metastatic castrate-resistant prostate cancer
Side effects are typically immune-based
What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.
Osteoporosis
Dyslipidaemia
Weight gain
BMD
Mood
Insulin resistance
CVS morbidity / mortality
What is the significant side effect of V600E inhibitors such as vemurafenib?
Hand-foot syndrome
How do the presence of brain mets impact upon melanoma treatment?
1-3 mets - stereotactic surgery (SRS) or surgery
> 3 mets - BRAF inhibitors or immunotherapy
Name 6 indications for BRCA testing in breast Ca.
<40 years old
“Triple negative” pathology <50 years
Bilateral breast Ca, one <50 years
Male breast cancer
Jewish ancestry
Family history of ovarian cancer
Name 3 indications for BRCA testing in ovarian Ca.
<70 years
Jewish ancestry
Family history of breast or ovarian cancer
What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.
Breast
- offer bilateral mastectomy (best age <40)
- offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
- offer screening - annual MRI/MG from age 30 (MG only from 50)
Ovarian
- RRSO once family complete or <35 (BRCA1), <45 (BRCA2)
No evidence for screening benefit
How do PARP inhibitors work?
Cell death via synthetic lethality
PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.
What are side effects of PARP inhibitors? Name 4.
Nausea
Diarrhoea
Fatigue
Abdominal pain
How does sentinel node biopsy help inform treatment plans for breast Ca?
Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required
1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast
> 2 sentinel nodes - axillary dissection improves local control
What chemotherapy agents are typically used for breast cancer?
Anthracycline (doxorubicin, epirubicin) best in meta-analyses
Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone
2 weekly dose dense chemotherapy better than 3 weekly
Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year
How does alcohol impact upon chemotherapy-induced emesis?
High ETOH is protective
For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?
RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone
RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment
RS >25 - chemo + hormonal therapy
What are side effects of tamoxifen? Name 2.
Increased DVT/PE
Increased risk of uterine cancer
Describe the interaction between SSRIs and tamoxifen.
Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine
Name 3 side effects of aromatase inhibitors.
Menopausal symptoms
Arthralgia
Accelerated osteoporosis
What is sipuleucel T, and how is it used?
Patient’s own immune cells (APCs) used and combined with prostatic acid phosphates and GM-CSF fusion protein, before being returned to the patient
Used for metastatic castrate-resistant prostate cancer
Side effects are typically immune-based
What are the late effects of long term hormonal deprivation for prostate cancer therapy? Name 7.
Osteoporosis
Dyslipidaemia
Weight gain
BMD
Mood
Insulin resistance
CVS morbidity / mortality
What is the significant side effect of V600E inhibitors such as vemurafenib?
Hand-foot syndrome
How do the presence of brain mets impact upon melanoma treatment?
1-3 mets - stereotactic surgery (SRS) or surgery
> 3 mets - BRAF inhibitors or immunotherapy
Name 6 indications for BRCA testing in breast Ca.
<40 years old
“Triple negative” pathology <50 years
Bilateral breast Ca, one <50 years
Male breast cancer
Jewish ancestry
Family history of ovarian cancer
Name 3 indications for BRCA testing in ovarian Ca.
<70 years
Jewish ancestry
Family history of breast or ovarian cancer
What should be offered to patients carrying BRCA mutations? Name 3 things for breast Ca, and one for ovarian Ca.
Breast
- offer bilateral mastectomy (best age <40)
- offer risk-reducing salpingo-oophorectomy (not useful for BRCA1; most are ER/PR -ve)
- offer screening - annual MRI/MG from age 30 (MG only from 50)
Ovarian
- RRSO once family complete or <35 (BRCA1), <45 (BRCA2)
No evidence for screening benefit
How do PARP inhibitors work?
Cell death via synthetic lethality
PARP1 is responsible for base-excision repair. BRCA is responsible for homologous recombination, another mechanism for DNA repair. However, homologous recombination does not occur with a BRCA mutation in place. With both PARP1 and BRCA pathways not intact, no DNA repair occurs, resulting in cell death.
What are side effects of PARP inhibitors? Name 4.
Nausea
Diarrhoea
Fatigue
Abdominal pain
How does sentinel node biopsy help inform treatment plans for breast Ca?
Negative sentinel node (70% of patients) - better prognosis overall and no further surgery required
1-2 sentinel nodes involved with cancer - no benefit for axillary dissection noting most get radiotherapy to breast
> 2 sentinel nodes - axillary dissection improves local control
What chemotherapy agents are typically used for breast cancer?
Anthracycline (doxorubicin, epirubicin) best in meta-analyses
Addition of taxane (paclitaxel, docetaxel) improves on anthracycline alone
2 weekly dose dense chemotherapy better than 3 weekly
Concurrent trastuzumab (Herceptin) in HER2 positive improves disease free survival and survival; standard treatment duration one year
How does alcohol impact upon chemotherapy-induced emesis?
High ETOH is protective
For women with ER +ve breast Ca, how is risk stratified via Oncotype Dx?
RS <11 - 1% chance of recurrence at 5 years with endocrine treatment alone
RS 11-25 - no benefit from addition of chemotherapy to endocrine treatment
RS >25 - chemo + hormonal therapy
What are side effects of tamoxifen? Name 2.
Increased DVT/PE
Increased risk of uterine cancer
Describe the interaction between SSRIs and tamoxifen.
Blocking of CYP2D6 reduces active tamoxifen metabolites by SSRI - avoid concurrent fluoxetine or paroxetine
Name 3 side effects of aromatase inhibitors.
Menopausal symptoms
Arthralgia
Accelerated osteoporosis
