Med Onc Bits Flashcards
(29 cards)
Name some applications of Durvalumab for lung Ca (and trials and benefit, who does it not benefit, alternative drug trial ongoing, typical dosing)
This card fucking sucks.
1) Adeno:
Pacific - Stg III and stable after standard treatment (e.g 55/20) and 2 cycles platinum.
1 yrs of q2week Durv = 66% 2yr OS vs 56%, also DMFS including decreased mets to the noodle.
No benefit in EGFR+
LAURA trial suggests Osimertinib may be even better with high PFS rates OS data soon (at 3 years)/
2)SCLC:
LS - Adriatic - 3yr OS 60%
ES - Caspian - Increase OS 3 months to 13months from 10months
A NSCLC may (with debate) be considered for chemo at what stage?
When is chemo generally always indicated?
Most common regimen?
Give doses:
T2b = 4cm, NO = Stage IIA
Stg III = begins at T1-T4N1 or T4NO,
Common regimen:
1) Weekly Cisplatin (50mg/m2 D1) + Q4W Etoposide (50mg/m2 D1-5, and D29-33)
2) Weekly Carboplatin (2AUC) and weekly Paclitaxel (45mg/m2)
Capecitabine:
1) uses
2) MOA/Class
3) Side effects
1) Concurrent with RT:
- Rectum LC and TNT: BD 825mg PO (alt continuous 5-FU) - obviously not if dMMR tumour
- Anal MMC (essential) and either 5-FU or capecitabine)
2) Converts to 5-FU which among other things targets thymidylate synthase decreasing nucleotide for DNA synthesis.
3) Classic side effect Hand Foot Mouth occurs in ~5% much more common than in 5-FU. Other side effects (typically to a lesser degree than 5-Fu) Stomatitis/mucocitis, nausea, diarhoea, gastritis, abdominal pain. Rarer - clinically significant/High risk neutropenia.
5-FU:
1) uses
2) MOA/Class
3) Side effects
1) Uses:
Bladder (D1 MMC and 5-FU 2.5g/msq, D15 5-FU)
Anal (MMC essential) + 5-FU or capecitabine
Rectum LC and TNT: BD 825mg PO (alt continuous 5-FU) - obviously not if dMMR tumour
Adjuvant for Her2-ve (biggest benefit x3neg) with partial response to NA
2) Among other things targets thymidylate synthase decreasing nucleotide for DNA synthesis.
3) Mucocitis most common, classic is coronary artery spasm, hand foot and mouth (less common than capecitabine).nausea, diarhoea, gastritis, abdominal pain. Rarer - clinically significant/High risk neutropenia.
Current Gold Standard preoperative approach to esophagus and gastric cancer?
Describe the cycles
Adeno:
Esopec = FLOT 5% 3yr OS benefit over
FLOT is 5-FU, Leucovin, Oxaliplatin Docetaxel. 8 2 week cycles total. 4 pre, 4 6-12 weeks post.
CROSS: RT concurrent with Carboplatin + Paclitaxel.
For each of these systemic therapies give the side effects for which they are famous:
Taxanes
Cisplatin
Carboplatin
Oxaloplatin
5-FU
Capecitabine
Etoposide
Ritux
Cetuxumab
Taxanes: Perif oedema (docetaxel). Perif neuropathy (Paclitaxel more common)- cardiomyopathy if used with Acanthracycline. Myelosuppression - typically neutropenia. Complete allopecia,
Cisplatin: Neuropthy, ottotoxicity, nephropathy, N&V
Carboplatin: Myleosuppression
Oxaloplatin (e.g adj rectal ca) famous for peripheral neuropathy - 90% peaks at 6months. 50% Pts some residual @2yrs
5-FU: Mucocitis, hand foot and mouth - like rash, coronary artery spasm
Capecitabine: Is converted to 5-FU
Etoposide: Myleosuppression
Ritux: Super COVID
Cetuxumab: Skin rash - 95% of the time.
A 45yro woman with tripple neg T3N2 breast cancer was found to have a partial response at mastectomy. What should her treatment include and why?
CREATE-X
Her 2neg with incomplete PR:
Adjuvant capecitabine.
Improves DFS and OS - in particular in women with x3 negative disease. %yr OS 79 vs 70%
What evidence is there for chemo for a patient with oncotype int risk (i.e. score less than?) ER/PR+ve Her2-ve disease with 3 or less nodes positive?
RX-PONDER:
For post menopausal women.
No benefit (on any subtype)
For pre-meno a small invasive disease free survival benefit (IDFS)
*IDFS though more specific than DFS, especially where recurrence rates are low - allowing disambiguation of what occured - i.e. IDC vs lobular. And therefore a more “meaningful” clinical outcome within the context of the clinical study.
What is TPF chemo?
TPF (docetaxel, cisplatin, fluorouracil) is the standard chemotherapy used for induction in locally advanced head and neck squamous cell carcinoma (LAHNSCC).
Its toxicity limits it to younger patients with good functional status and without significant comorbidity.
Use is somewhat controversial for this
Cisplatin:
1) uses
2) MOA/Class. Mechanisms of resistance and preferred chemo when this occurs.
3) Side effects
1) H&N: Weekly D1 40mg/msr or more toxic but favoured 100mg/msq q3week
2) Non-cell cycle specific toxicity: Binds DNA, forming adducts that lead to DNA damage and ultimately cell death, primarily apoptosis.
While there is often an initial brisk response, cisplatin-resistance is common and may involve a number of mechanisms: efflux pumps, increased DNA repair. Paclitaxel is chem to change to in this setting.
3) Nephro, neuro, ototoxicity post-chemo cognitive impairment. Electrolyte derrangements = low Mg, Ca, and K. Others = nausea.
2 examples of PD-1 inhibitors.
1 made-up example.
2Examples of PD-L1:
PD1:
Pembro: fucken heaps
NIvo: Melanoma as part of dual T-cell (i.e. with CTLA4 ipi)
P-diddyluzimab: Pembroluzimab + Baby oil
PD-L1:
Durvalumab:
Avelumab: Merkel’s- under investigation
Atezolizumab: SCLC
Gemcitabine:
Classic uses
Was previously Key chemo in resectable/borderline pancreas (PRODIGE inferior to FOLFURINOX).
Could be given in borderline 1cycle then 2 cycles concurrent w/36Gy/15#s.
More commonly as a 2ndline:
Bladder - cisplatin+gem
Pancreas: if FOLFURINOX 1st line
Breast: Recurrent after AC in tripple neg - gemcitabine + carbo + pembro.
Gemcitabine MOA:
Anti metabolite. activated pro drug interferes with DNA synthesis.
Key toxicities associated with taxanes:
Differentiate between docetaxel and paclitaxel
Classic toxicities:
Myelosuppression (primarily neutropenia),
complete alopecia,
hypersensitivity reactions.
Peripheral neuropathy and myalgias/arthralgias can also occur, though these are more commonly observed with paclitaxel.
Docetaxel is known for fluid retention (edema, ascites, pleural effusions), which can be mitigated with prophylactic corticosteroids.
& Acral Erythema
MOA for taxanes:
inhibits cell division by preventing microtubules from breaking down (by stabilising them) -> cell arrest at mitosis ->apoptosis/cell death.
Compare Cisplatin to Carboplatin in terms of toxicity:
In comparison with cisplatin, carboplatin is less nephrotoxic and less emetogenic.
Neurotoxicity and ototoxicity are minimal or absent for carbo.
Its major and dose-limiting toxicity is myelosuppression, particularly thrombocytopenia.
Carboplatin is a useful alternative in situations where cisplatin is contraindicated and this is not universally at the expense of efficacy.
Mechanisms of platinum resistance:
Key are increased DNA repair, efflux pumps.
Also implicated increased metabolism/excretion, decreased cellular influx.
Is Herceptin safe with radiation.
Yes, trastuzumab can generally be used safely with radiotherapy in patients with breast cancer, especially in the adjuvant setting. Studies have shown that concurrent use of trastuzumab and radiotherapy does not significantly increase the risk of cardiac toxicity.
Herceptin cardiomyopathy is reversible, and radiation does not increase this risk anyway.
MOA adriamycin cardiac toxicity:
Anthracycline-induced cardiotoxicity is due in large part to the generation of free radicals from doxorubicin through mitochondrial redox cycling of doxorubicin in the cardiomyocyte, which ultimately results in left ventricular dysfunction, and in the most severe cases, congestive heart failure
Mechanism of action for Osimertinib? Older alternatives?
Mutations associated with resistance to alternatives?
Most common side effects?
OsimERtnInb - has better CNS penetrance than older (Erlotinib, Getfitinib, possibly slower resistance).
15% (white ppl) to 50% (yellow ppl) of lung adeno Have EGFR mut. Most commonly Exon 19 or 21associated (40% each).
T790M (Exon 20) is a mutation that causes resistance, or can have it at Dx - in which case only 5% response to Osi. BUT T790M mutation are less aggressive than tumour with EGFR TKI resistance due to other mechanisms
Osi side effects: Acne/rash, dry skin, diarrohoea (fuck with EGFR get gastro - like cetux).
Serious:
Resp - pneumonitis and ILD
Cardiac - long QT
For osimertinib give the common and serious side effects?
Common:
Acne
Rash
Gastritis/colitis
Serious:
Resp - pneumonitis and ILD
Cardiac - LongQT, CHF
BEACOPP serious side effects?
Infertility
Second malignancy - the main cause of death: E.g. AML
-Chemo-
Cell cycle phase specific chemo (CCPS) classes:
ANtimetabolites - work in the S Phase:
E.g. Methotrexate.
5-FU/Capecitabine
S and G2:
Topoisomerase II inhibitors (topoisomerases separate strands of DNA. Drugs the ability of the cell to copy DNA): Etoposide
G2:
- Bleomycin
- Etoposide
Mitotic inhibitors (plant alkaloids):
- Taxanes (i.e stabilise tubules)
- Vinca alkaloids: Vinblastine, Vincristine
NOTE: Corticosteroids inhibit G1…
-Chemo-
Cell cycle phase non-specific chemo (CCPNS) classes:
Why is it important?
1) SOME Alkylating agents:
- cyclophosphamide (nitrogen Mustard)
1.1) Platinum drugs: Cisplatin, carboplatin, oxaliplatin
2) Anti-tumour antibiotics
Anthracycline antibiotics:
Doxorubicin
Epirubicin
Current chemotherapy regimens tend
to combine CCPS and CCPNS drugs for
maximum efficacy and cancer kill potential.
