Med Onc Bits Flashcards
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 neuropathy - cardiomyopathy if used with Acanthracycline.
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
