Caprelsa

Vandetanib (Vandetanib) instruction manual
Common name: Caprelsa
Trade name: Vandetanib
Full names: Vandetanib, Vandetanib tablets, Vandetanib, Caprelsa, Zactima, ZD6474

Indications:
1. Vandetanib is a kinase inhibitor suitable for the treatment of symptomatic or progressive medullary thyroid cancer that is unresectable, locally advanced or metastatic. Because vandetanib has treatment-related risks, use of vandetanib in patients with indolent, asymptomatic, or slowly progressive disease should be considered with caution.
2. Mutations in these targets also exist in patients with non-small cell lung cancer, so this drug is also used in patients with lung cancer with specific gene mutations. In clinical studies of non-small cell lung cancer, some researchers even call it "Iressa second generation". At present, vandetanib is only used clinically for medullary thyroid cancer.

Usage and dosage:
Thyroid cancer and lung cancer: 300 mg orally, once a day. It can be taken with or without food, and cannot be crushed. It can be placed in 60ml of water and stirred for about 10 minutes to disperse (not completely dissolved) before being taken immediately or administered through a nasogastric tube or gastrostomy tube. The remaining residue can be mixed with 120ml of water and administered.

Adverse reactions:
Well tolerated when ≤300mg/d. The most common toxicities are diarrhea, rash, nausea, hypertension, anorexia, asymptomatic QT prolongation, and proteinuria; with increasing dose. Hypophosphatemia, folliculitis, elevated transaminase, non-specific intestinal obstruction, thrombocytopenia, congestive heart failure, deep vein thrombosis, pulmonary embolism, etc. may occur. The most common dose-limiting toxicities (DLTs) were diarrhea, hypertension, and rash.
Common (more than 10%) adverse reactions of Vandetanib include cold, bronchitis, upper respiratory tract infection, urinary tract infection, decreased appetite, insomnia and depression, dizziness, blurred vision, long QT syndrome, high blood pressure, stomach pain, diarrhea, nausea, vomiting, indigestion, rash, acne, dryness and itching, protein in urine, kidney stones, weakness, fatigue, pain and edema.
Vandetanib is common (accounting for 1 % to 10% of people) adverse reactions include pneumonia, sepsis, influenza, cystitis, sinusitis, laryngitis, folliculitis, kidney infection, low thyroid hormone levels, low potassium, high calcium levels, low sodium levels, anxiety, tremors, drowsiness, unconsciousness Loss of consciousness, balance disorder, changes in taste, visual impairment, halo vision, corneal disease, hypertensive crisis, nose bleeding, hemoptysis, colitis, dry mouth, stomatitis, constipation, gastritis, painful urination, hematuria, renal failure, frequent urination, fever.

Contraindications:
Do not use in patients with congenital long QT syndrome.

Notes:
1. Monitor electrocardiogram and serum potassium, calcium and TSH levels 2-4 weeks and 8-12 weeks after starting vandetanib treatment, and every 3 months thereafter and after dose adjustment. When dose reduction is appropriate.

2. Severe skin reactions may lead to death, and vandetanib should be permanently discontinued.

3. Patients with non-specific respiratory signs and symptoms such as hypoxia, pleural effusion, cough, or dyspnea. It is recommended to report respiratory symptoms promptly.

4. Vandetanib should be discontinued in the event of severe ischemic cerebrovascular events, bleeding, heart failure, diarrhea, hypothyroidism, hypertension, and reversible posterior leukoencephalopathy syndrome.

5. Vandetanib may be fatal if given to pregnant women. Advise women to avoid pregnancy for 4 months after treatment with vandetanib.

6. Because QT prolongation increases the risk of torsade de pointes and sudden death, vandetanib can only be obtained through the strict allocation plan (vandetanib REMS) plan. Only certified prescribers and pharmacies can dispense vandetanib.

Storage:
Sealed.

Mechanism of action:
Vandetanib is a kinase inhibitor. In vitro studies have shown that vandetanib inhibits the activity of tyrosine kinases including epidermal growth factor receptor (EGFR), vascular growth factor receptor (VEGFR), rearrangement during transfection (RET), members of protein kinase 6 (BRK), TIE2, members of the EPH receptor kinase family, and members of the tyrosine kinase Src. Vandetanib inhibits endothelial cell migration, proliferation, survival and neovascularization in an in vitro angiogenesis model. Vandetanib inhibits epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells.

In vivo Vandetanib administration reduced tumor cell-induced angiogenesis, tumor vascular permeability, and inhibited tumor growth and metastasis in mouse tumor models.

Efficacy and Safety:
A double-blind, placebo-controlled study randomized patients with unresectable locally advanced or metastatic medullary thyroid cancer to vandetanib 300 mg (n=231) compared with placebo (n=100). The primary objective of the study was to show improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other endpoints include overall survival and overall objective response rate (ORR). Centralized, independent blind review was used to evaluate the PFS and ORR results of imaging data. Based on the investigator's assessment of objective disease progression, patients were discontinued from the blinded study and elected to receive open-label vandetanib. After disease progression, 19% (44/231) of patients initially randomized to receive open-label vandetanib, and 58% (58/100) of patients initially randomized to placebo elected to receive open-label vandetanib after disease progression. Analyzes in the subgroup of patients with symptoms or progression within the first 6 months showed similar PFS results (HR = 0.31 95% CI: 0.19, 0.53 for symptomatic patients; HR = 0.41 95% CI: 0.25, 0.66 for patients with progression within the first 6 months).

In the primary analysis of PFS, 15% of patients had died and there was no significant difference in overall survival between the two treatment groups. The overall objective response rate (ORR) was 44% in patients randomized to vandetanib compared with 1% in patients randomized to placebo. All objective responses were partial responses.

Study 003 compared vandetanib 300 mg/d with gefitinib 250 mg/d in the treatment of advanced NSCLC (non-small cell lung cancer) mg/d efficacy in 168 patients with advanced NSCLC who failed first-line or second-line chemotherapy. Compared with gefitinib, vandetanib significantly increased the response rate and prolonged the disease progression-free survival time by 8% and 1%, respectively, 11.9 weeks and 8.1 weeks (P=0.011). In clinical trials, patients are allowed to change their treatment regimen if their disease progresses or they cannot tolerate toxicity.

The trial results showed that the disease control rate of patients who used gefitinib instead of vandetanib was 14%, while the disease control rate of patients who used vandetanib instead of gefitinib reached 32%. The expected median overall survival was 6.1 months from vandetanib → gefitinib, and 7.4 months from gefitinib → vandetanib. Study No. 0007 is ongoing and aims to evaluate the efficacy of vandetanib combined with paclitaxel (200 mg/m2) + carboplatin (AUC=6) in the first-line treatment of stage IIIB-IV NSCLC. Preliminary trial results show that vandetanib can be combined with traditional chemotherapy drugs to treat NSCLC without significantly increasing grade 3 to 4 adverse reactions.