Hi ,

Welcome back to the Oncology Insights Newsletter which fosters your continuous growth in oncology pharmacy practice

Last time you learned about the passion tax, different types of genetic mutations, and a Thanksgiving reminder

This week you'll learn about hand-foot syndrome, treatment in the 4 clinical stages of pancreatic cancer, and why language matters

Have a great week!

Kelley

🧠 IPS (Insight, Pearl, Sundry)

Insight

A patient on capecitabine presents with uncomfortable, red, swollen palms that look like they were out in the sun ☀️ for too long

What is this?

Capecitabine (the oral prodrug of 5-fluorouracil) is an antimetabolite - it’s structure resembles the pyrimidine uracil which helps it interrupt DNA and RNA synthesis to shut down cell replication

Capecitabine is known for causing hand-foot syndrome (HFS) which is dryness, redness, and swelling of the palms of the hands and soles of the feet - Google image it, it looks like a sunburn

As you can imagine, this is very uncomfortable and can cause treatment interruptions

Historically, the most important prevention is to keep these areas well moisturized, but there has also been a study looking at topical diclofenac

The D-ToRCH study randomized 264 patients on capecitabine to prophylaxis with 1% topical diclofenac or a placebo gel. The primary outcome was grade 2+ of HFS.

Any grade HFS was lower in the diclofenac group (6.1% vs 18.1%) as well as grade 2/3 HFS (3.8% of vs 15%, 95% CI 4.3-18.1, p=0.003)

Patients that received diclofenac also had fewer dose reductions 🙌

Less than 20% of patients had any HFS in this study and given how uncomfortable it is for patients and that it can lead to dose reductions which we want to avoid if we can, this is an easy intervention to make to reduce this toxicity

Pearl

Pancreatic cancer is one of those diseases that carries its own black cloud - anytime you hear the name you know it’s not good

And that’s because survival is very poor - 5 year overall survival for all stages is ~13%. It’s better for localized disease (~44%), but not many patients are diagnosed that early given that it’s often asymptomatic.

When thinking about treatment options, we first need to understand that staging is different in pancreatic cancer. Although most solid tumors use the TNM system, pancreatic cancer is staged clinically into 4 groups: resectable, borderline resectable, locally advanced, and metastatic.

These stages show you the importance of surgery - the only chance of a cure is a full resection but not many patients present with resectable disease

These clinical stages are what guide treatment so let’s review them

Resectable

Pharmacists likely won’t see these patients until after surgery since they are going to the operating room fast if they are in this category. The surgery is the very extensive Whipple procedure which means even if patients have resectable disease, they may have comorbidities preventing them from getting the surgery.

Even if the surgeon thinks they removed all the tumor, we know recurrence rates are very high so these patients will get adjuvant therapy. Options include mFOLFIRINOX, which is reserved for fit patients with an ECOG of 0/1 because it’s tough to tolerate, or gemcitabine + capecitabine. Both are preferred and category 1 recommendations.

Borderline Resectable

Since surgery is the only cure, we want to get the patient to surgery if possible so those in this stage will get neoadjuvant therapy, anywhere from 2-6 cycles, followed by 6 months of adjuvant after surgery. Preferred regimens are mFOLFIRINOX, gemcitabine + nab-paclitaxel, or for those with a BRCA or PALB2 mutation, gemcitabine + cisplatin.

During adjuvant treatment, you may see regimens being changed or radiation being added as we try to get a better response. The addition of radiation hasn’t been shown to improve survival but it can improve local control.

Locally Advanced

These patients are getting systemic therapy, sometimes with radiation. Which regimen depends on their performance status, age, and comorbidities. The common options include mFOLFIRINOX, gemcitabine + nab-paclitaxel, and gemcitabine + cisplatin (BRCA or PALB2+). NALIRIFOX is in the picture here too but it’s not used often due to the cost. This is what NCCN has to say about it:

“While NCCN recognizes that there is high-level evidence supporting the use of NALIRIFOX over gemcitabine and albumin-bound paclitaxel, it should be recognized that this regimen does not appear to have an advantage over FOLFIRINOX and adds considerably more expense compared to FOLFIRINOX.”

I have to say, it’s kind of cool when NCCN lays it out like that 😂

These treatments hopefully achieve disease control but given the aggressive nature of the disease and high likelihood of recurrence, patients are often treated with a maintenance regimen of a single agent like gemcitabine. This is not necessarily guideline driven but is done in practice. In the words of my pancreatic expert, Makenna Smack, “we know pancreatic cancer won’t slow its roll”.

Metastatic

Unfortunately, most patients present here and the treatment goal is to achieve disease stability and maintain quality of life

Options include mFOLFIRINOX, gemcitabine + nab-paclitaxel (or cisplatin for those with BRCA/PALB2), or NALIRIFOX (same caveat from NCCN applies here despite it having a category 1 recommendation). Once they progress, you switch therapies. If you started with a gemcitabine-based regimen due to performance status, you might give FOLFOX or FOLFIRI if they can’t tolerate mFOLFIRINOX. We don’t use a lot of radiation in metastatic disease unless patients have localized metastatic sites.

I’ve mentioned patients with BRCA or PALB2 mutations so genetic testing is important in these patients. If they are BRCA+, they need exposure to a platinum agent (either the oxaliplatin in mFOLFIRINOX or cisplatin with gemcitabine) and olaparib. Olaparib maintenance is given after 4-6 months of disease stability.

If they are positive for other mutations (which are not super common), they would qualify for those targeted disease-agnostic therapies (NTRK, BRAF V600E, MSI-H, RET).

Sundry

I was out of the country on election day

Before voting early, I looked at a sample ballet and was surprised at how a particular issue was described. It was written in a way that was more confusing than it should have been. If you didn’t do your own research ahead of time, the ballot language would not of helped you understand what you were being asked to vote on.

Language matters

In healthcare, we have a steep language barrier - lots of terms, acronyms, and slang that is used regularly

In pharmacy, people use both chemical/generic and brand names as well as abbreviations. It’s hard enough the remember drug names when you’re new to oncology, let alone when you hear pembro, nivo, carbo, doxo, and liso-cel.

I know brand names are often easier to pronounce, and that’s by design; their manufacturers want you to use their name - marketing 101!

Using the chemical name and not using abbreviations or slang helps others understand what kind of drug is being discussed and ensures clear communication, which benefits everyone given how fast this industry is moving!

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