Ashley & Brooke Barlow PharmD Profile picture
May 27, 2021 12 tweets 5 min read Read on X
Alert 🎙Pharmacy Grand Rounds Thread Ahead! 🚨

Last week I had one of my final presentations of the year! With a catchy title😉

Urine for an Update! Updates in the management of metastatic urothelial cancer

Hold your bladders, this is an extensive update! 😂
#oncopharm Image
Bladder cancer can be divided into two ✌️subtypes:
1) Non-muscle invasive: encompasses in-situ and localized disease➡️5-yr OS >70%

2) Muscle invasive: encompasses regional or metastatic disease➡️5-yr OS dismal especially for metastatic disease 😔 Image
Cisplatin=SOC
50% of pts w are ineligible due to older age👵🏻, poor PS, ⬇️ renal function, ⬇️hearing, neuropathy, heart failure 🫀& other comorbities that ⬆️ risk of ⚠️

Carboplatin yields inferior responses➡️NOT 🙅🏻‍♀️ an equal alternative due to ⬇️ OS😢➡️pt left w/minimal tx options Image
Luckily 👍🏼 there has been a tsunami 🌊 of new therapies approved for mUC in the recent decade: my presentation discussed the orange treatments in detail below! Image
1st: Pembro/Atezo to provide pts who are cisplatin inelidgble improved tx💊options
✅median OS > what we see 👀 with carbo (‼️indirect comparison‼️)

However an important POINT to CHECK(no pun intended)is PDL1 status➡️indicated only for PDL1+ pts unless ineligible for all chemo Image
The most predominant advancement in mUC is maintenance avelumab

JAVELIN Bladder 100➡️7 month improvement 🏆in OS compared to BSC➡️1st maintenance therapy for mUC!

Please 👀 advantages and disadvantages below! Image
💊1st targeted🎯tx for mUC‼️

Erdafitinib➡️pan-FGFR inhibitor❌approved for 2nd/3rd line mUC in for pts w/ susceptible FGFR3/2 genetic alterations

FGFR expressed in ~15% of mUC pts, studied in phase 2 trial BLC2001 ORR of 40% (improved ORR vs chemotherapy which yields~8-13% ORR) Image
One☝🏻cool😎 fact about erdafitnib➡️FGFR found in apical membrane of renal tubules➡️❌exchange of Phos/Na leading to hyperphosphatemia (👀👇🏻)

Interestingly🧐associated w/tx response😮

Dose titration req (8mg/d➡️14 days➡️9mg/d if phos <5.5mg/dL)
⚠️caution renal imp or hyperCa⚠️ ImageImage
Enfortumab-vedotin: antibody-drug conjugate🎯nectin-4 (expressed in 93% of mUC) bound to MMAE (microtubule distrusting agent🧬)

EV-301 phase 3 trial of EV in the 3L setting➡️30% RR for death 🤯

Ongoing studied looking at EV in earlier lines of tx & combined with immunotherapy! ImageImage
Big AE to monitor for with EV are
1️⃣Hyperglycemia🍭(1💀 due to DKA on trial)
2️⃣ 👀disorders (dry eye, keratitis: Rx💊ocular steroid)
3️⃣Neuropathy: like brentuximab-VEDOTIN, the MMAE results in peripheral neurop
4️⃣Skin: nectin-4 expressed ubiquitously in skin➡️🔎 for SJS/TEN⚠️
How to decide between novel therapies? 🧐

✅Favors EV: retinal disorder (BBW for central serous retinopathy for erda), concern for adherence, absent FGFR (only found in 15%!), CKD/hyperCa due to hyperphosphatemia risk

✅Favors erdafitnib: uncontrolled DM, prefers oral tx, PN! Image
Thank you for viewing! Feel free to add your thoughts💭 about novel updates in mUC! #oncopharm #bladdercancer #immunoOncology #TwitteRx

• • •

Missing some Tweet in this thread? You can try to force a refresh
 

Keep Current with Ashley & Brooke Barlow PharmD

Ashley & Brooke Barlow PharmD Profile picture

Stay in touch and get notified when new unrolls are available from this author!

Read all threads

This Thread may be Removed Anytime!

PDF

Twitter may remove this content at anytime! Save it as PDF for later use!

Try unrolling a thread yourself!

how to unroll video
  1. Follow @ThreadReaderApp to mention us!

  2. From a Twitter thread mention us with a keyword "unroll"
@threadreaderapp unroll

Practice here first or read more on our help page!

More from @theABofPharmaC

Jan 7, 2022
Time ⏰ for Part #2 of the Tweetorial 🧵 on the DDI btwn PHT & VPA with a focus on drug metabolism 💊🔄

If you haven’t seen it yet - check out Part 1 by @JimmySuhMD on the albumin interaction btwn PHT & VPA
 
However, that’s only half of the story!⚠️
 
1/n First, let’s discuss basics on phases of drug metabolism 🔄
 
Phase I: Oxidation (ex. CYP450 enzymes)
 
Phase II: Conjugation (ex. Glucuronidation)
 
🎯 Goal 👉🏻 covert drug to an active (pro-drug) or inactive metabolite and ⤴️ solubility ➕ ⤴️drug elimination via urine/bile
2/n What are the key 🔑 metabolic pathways for VPA?

There’s 3️⃣ big ones
 
Phase1️⃣ (~10%)
➢ Substrate of CYP2A6, CYP2B6, CYP2C9
➢ *4-ene metabolite▶️ hepatotoxic ⚠️
 
Phase2️⃣ (~30 – 50%)
➢ Conjugation via glucuronosyltransferase
 
Other▶️Mitochondrial β-oxidation (~40%)
Read 12 tweets
Nov 30, 2021
A #MedTwitter🧵on the frequently obtained, but ever mysterious🕵️‍♀️ Procalcitonin (PCT) 🦠

💡 What is it?
💡 Where does it come from?
💡 What factors/comorbid conditions may impact PCT?

#IDTwitter #TwitteRx
1/n First, let’s discuss the normal, physiologic role of PCT 🧬

✨116 chain amino acid
✨Neuroendocrine hormone
✨Produced by thyroid C-cells
✨Enzymatically cleaved to calcitonin
✨ Regulate Ca+2 & PO4- homeostasis

DOI 10.1093/ajhp/zxaa089

@AJHPOfficial @SESmithPharmD Image
2/n Why/How does PCT ⤴️ in bacterial infections?

✨Nonendocrine tissues (adipocytes, spleen, pancreas, etc) produce PCT but LACK 🛑 enzymes to cleave to calcitonin

✨Stimulus for non-thyroid PCT production include
1️⃣LPS/bacterial toxins ⚠️
2️⃣Cytokines (IL6, TNFa, ILb) Image
Read 9 tweets
Sep 21, 2021
Let’s talk CSF 🧠 💦

☝️ What is it & why is it important?
✌️ Key considerations in CSF sampling 🧪 & analysis 🧐 for suspected infection 🦠

A #NeuroTwitter 🧵 inspired by bedside rounds with attending @BuslKatharina & NCC team👏🏻
So to start, what is CSF? 🤔

CSF▶️clear, sterile fluid secreted by choroid plexus 💦 in the ventricles ➡️circulates throughout the subarachnoid space🧠 & spinal canal🦴

⭐️Function▶️ protective barrier 🛡 provides nutrients 🍎& facilitates removal toxins/metabolic byproducts⚠️
Now, let’s discuss🖐key pearls when analyzing CSF🧐for poss infection🦠

1️⃣Consider the source!

Obtained from a…
▶️“Closed”system, ie LP💉?
▶️“Open”system, ie EVD🧠?

⚠️Interpret CSF💦from “open”sys w/caution▶️blood🩸& inflammation🔥from underlying condition are often present
Read 8 tweets
Aug 20, 2021
Now that the salty🧂debate on the TYPE of fluid to use in the ICU has largely been solved, how about the RATE of IVF? 🤔

Back to the BaSICS💦

✅The Balanced Solutions in Intensive Care Study📖 (BaSICS) ▶️compared 333mL/hr vs 999 mL/h

Does IVF rate impact 90-day mortality? 🤔
💡 10, 520 ICU pts randomized 🏥

Fluid volume:

1162 mL in the SLOW infusion group 💦
vs. 1252 mL in the FASTer group

🛑NO difference in☝️ outcome: 90-day mortality (HR 1.03, CI, 0.96-1.11)

🛑No difference in✌️outcomes: RRT, AKI, ventilator free days, ICU/hospital LOS
Notably, when reviewing this study, the baseline characteristics are a key 🔑 consideration

< 5% of the cohort in both groups had sepsis (⬇️ the generalizability in this population) 🦠

Patients with AKI or ESRD were excluded from the trial 💡
Read 5 tweets
Apr 26, 2021
What medications 💊 are should be avoided 🛑 or used with caution ⚠️ in patients with Myasthenia Gravis? 🤔

See 👀 the thread 🧵below⤵️ that summarizes an amazing grand rounds presentation by @UKPharmRes PGY1 @AliW_PharmD on key 🔑 medication considerations in MG
1️⃣Antibiotics to avoid or use w/caution🦠 💊

🛑FQs = FDA BBW for ⤴️ risk of MG crisis ➡️ avoid use if possible
⚠️ Macrolides ⤴️ rate of MG crisis (case reports)
⚠️ AG linked to ⤴️ ICU acquired weakness & exacerbate ‼️ MG crisis
📝Risk⬆️ w/neomycin vs. tobramycin & amikacin
Antibiotics considered to be SAFE alternatives to the above include

✅Beta-lactams
✅Tetracyclines
✅Linezolid
✅Bactrim

Ex. In an MG patient who presents 🏥 w/CAP 🫁 ➡️ choose ceftriaxone + doxycycline✅ OVER ceftriaxone + azithromycin🛑
Read 7 tweets
Mar 12, 2021
Urine Trouble: A review of Immune checkpoint inhibitor associated nephritis

See below some of the data I collected on this topic from a recent inservice! @OncoPharmPod #nephrotwitter #oncopharm
Immune checkpoint inhibitors (ICI) ➡️revolutionized tx 💊 of various malignancies
✅Treatment that offers some pts🙋🏻‍♀️a chance of cure🤯

Also see a range of unique toxicities⚠️➡️autoimmune in nature

An emerging one of which is nephritis! (Insert a needed kidney emoji)
Pathogenesis of ICI-nephritis is unknown

Some hypothesis exist 🧐
✅stopping the breaks on the immune system results in excessive immune activation➡️ATIN
✅Previous renal insult or concurrent medications that lead to ATIN can accelerate the emergence of renal injury ☢️
Read 8 tweets

Did Thread Reader help you today?

Support us! We are indie developers!


This site is made by just two indie developers on a laptop doing marketing, support and development! Read more about the story.

Become a Premium Member ($3/month or $30/year) and get exclusive features!

Become Premium

Don't want to be a Premium member but still want to support us?

Make a small donation by buying us coffee ($5) or help with server cost ($10)

Donate via Paypal

Or Donate anonymously using crypto!

Ethereum

0xfe58350B80634f60Fa6Dc149a72b4DFbc17D341E copy

Bitcoin

3ATGMxNzCUFzxpMCHL5sWSt4DVtS8UqXpi copy

Thank you for your support!

Follow Us!

:(