培米替尼的功效与作用及副作用？

It is a small molecule tyrosine kinase inhibitor that mainly targets receptors of the fibroblast growth factor receptor (FGFR) family. FGFR plays an important role in cell growth, differentiation, migration, and angiogenesis. In some patients with cholangiocarcinoma, the FGFR gene may have abnormalities, such as fusion or rearrangement, and these abnormalities are related to tumor development.

Efficacy and role of pemetinib

1. Targeted inhibition of the FGFR signaling pathway: pemetinib competitively binds to the ATP binding site of FGFR1/2/3, inhibiting the phosphorylation and signaling of FGFR, thereby preventing the growth and spread of tumor cells.

2. Inhibit tumor proliferation: Pemetinib can directly inhibit the proliferation and division of tumor cells and slow down the rate of tumor growth.

3. Inhibit angiogenesis: In addition to directly acting on tumor cells, pemetinib may also inhibit the development of tumors by inhibiting the angiogenesis process and reducing the blood supply to tumors.

4. Improve patients’ quality of life: Pemetinib has shown certain efficacy in the treatment of cholangiocarcinoma, which can delay disease progression, improve survival and improve patients’ quality of life.

Side effects of pemetinib

1. Skin and subcutaneous tissue diseases: alopecia, nail toxicity, dry skin, palmar and plantar dysesthesia syndrome.

2. Gastrointestinal diseases: diarrhea, nausea, constipation, stomatitis, dry mouth, vomiting, abdominal pain.

3. Systemic diseases: fatigue, peripheral edema.

4. Nervous system diseases: dysgeusia, headache.

5. Musculoskeletal and connective tissue diseases: joint pain, back pain, and limb pain.

6. Metabolic and nutritional diseases: hyperphosphatemia, anorexia, hypophosphatemia, and dehydration.

Measures to deal with the side effects of pemetinib

1. Nausea or vomiting: Nausea patients can use anti-nausea drugs, such as ondansetron, etc. as directed by the doctor. At the same time, pay attention to adjusting their diet, avoid eating greasy and spicy food, and drink more water to increase their fluid intake. If symptoms are severe, the drug may need to be temporarily discontinued or the dose adjusted.

2. Fatigue: Ensure adequate rest time, make appropriate adjustments to daily activities and work plans, and avoid overexertion.

3. Hair loss: Use mild shampoo and conditioner and avoid using irritating shampoo products. If hair loss is severe, you can consider wearing a wig.

4. Stomatitis: To maintain oral hygiene, you can use mouthwash to rinse your mouth.

5. Dry skin and itching: Use moisturizer to keep skin moist, and avoid excessive bathing and the use of harsh soaps and detergents.

6. Joint pain: You can use non-steroidal anti-inflammatory drugs as directed by your doctor to relieve pain, such as ibuprofen tablets, etc., and you can also perform physical therapy or hot compress on the local area.

Efficacy of pemetinib

In a single-arm phase 2 study, more than one-third of pretreated patients with advanced cholangiocarcinoma had an objective response after receiving once-daily pemetinib, and nearly half had stable disease. The median progression-free survival and overall survival at the time of final analysis were 7 months and 17.5 months, respectively.

Pemetinib was generally well tolerated and had a manageable safety profile. The most common treatment-related adverse events were only grade 1-2 in severity. Likewise, the severity of observed ocular and nail toxicities was rarely grade ≥3. Pending confirmation of clinical benefit in an ongoing controlled phase 3 study of cisplatin plus gemcitabine (FIGHT-302), pemetinib provides a valuable targeted therapy for pre-treated patients with advanced (I) CCA harboring FGFR2 fusions or rearrangements.

Recommended dosage

The recommended dose of pemetinib is 13.5 mg once a day for 14 consecutive days, followed by 7 days of discontinuation, for a total cycle of 21 days. Continue treatment until disease progression or unacceptable toxicity.

Summary

Patients should undergo regular blood and liver function tests while taking pemetinib to detect and manage possible side effects in a timely manner. If any discomfort occurs, patients should communicate with their doctor promptly so that the treatment plan can be adjusted. If you want to learn more about pemigatinib, you can read the article:

Reference:

Frampton JE. Pemigatinib: A Review in Advanced Cholangiocarcinoma. Target Oncol. 2024 Jan;19(1):107-114. doi: 10.1007/s11523-023-01024-x. Epub 2024 Jan 11. PMID: 38206555.

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