To help patients better understand and correctly use capapasetinib, the following detailed dosage guidelines are provided to ensure effective treatment of this innovative therapy.
Common Dosage Regimen for Adult Breast Cancer
Basic Dosage Regimen: 400 mg orally twice daily for 4 consecutive days, followed by a 3-day break. Continue until disease progression or unacceptable toxicity.
Precautions: Capapasetinib should be used in combination with fulvestrant. Please refer to the manufacturer's instructions for fulvestrant.
The interval between each dose is approximately 12 hours.
Patient Selection Criteria: Confirmation of at least one of the following gene alterations in tumor tissue—PIK3CA, AKT1, or PTEN—by testing.
For premenopausal and perimenopausal women, a luteinizing hormone-releasing hormone (LHRH) agonist should be administered according to current clinical standards.
For male patients, an LHRH agonist may be considered according to current clinical practice standards.
Indications: In combination with fulvestrant, this treatment is indicated for the treatment of locally advanced or metastatic breast cancer that is FDA-approved, PIK3CA/AKT1/PTEN gene-positive, HER2-negative, and where the patient meets one of the following criteria:
1. Progression after receiving at least one endocrine therapy regimen during the metastatic stage;
2. Recurrence within 12 months of the end of adjuvant therapy.
Dosage Adjustment:
Dosage Adjustment for Patients with Renal Impairment:
Mild to moderate renal impairment (creatinine clearance 30-89 mL/min): No dose adjustment required.
Severe renal impairment (creatinine clearance 15-29 mL/min): Data for this population are not yet established.
Dosage Adjustment for Patients with Hepatic Impairment:
Mild hepatic impairment (bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN, or bilirubin > 1-1.5 times ULN): No dose adjustment required.
Moderate hepatic impairment (bilirubin > 1.5-3 times ULN, with arbitrary AST levels): Caution is advised when using this medication; adverse reactions should be monitored (as exposure may increase).
Severe hepatic impairment (bilirubin > 3 times ULN, with arbitrary AST levels): Data for this population are not yet clear.
Stepwise dose reduction regimen for adverse reactions:
Initial dose reduction: 320 mg orally twice daily for 4 days, followed by a 3-day break.
Second dose reduction: 200 mg orally twice daily for 4 days, followed by a 3-day break.
If the patient cannot tolerate the second dose reduction, capapasetinib should be permanently discontinued.
Dose adjustment for specific adverse reactions:
Hyperglycemia
Fasting blood glucose (FG) > ULN and ≤ 160 mg/dL (8.9 mmol/L), or glycated hemoglobin (HbA1c) > 7%: Consider initiating or intensifying oral hypoglycemic therapy.
Fasting blood glucose 161-250 mg/dL (9-13.9 mmol/L): Discontinue administration until fasting blood glucose drops to 160 mg/dL (8.9 mmol/L) or below. If recovery occurs within 28 days, treatment can be restarted at the original dose; if recovery takes longer than 28 days, treatment should be restarted at a lower dose level.
Fasting blood glucose 251-500 mg/dL (14-27.8 mmol/L): Discontinue administration until fasting blood glucose drops to 160 mg/dL (8.9 mmol/L) or below. If recovery occurs within 28 days, treatment should be restarted at a lower dose level; if recovery takes longer than 28 days, medication should be permanently discontinued.
Fasting blood glucose >500 mg/dL (27.8 mmol/L) or life-threatening hyperglycemia-related sequelae occur: Discontinue administration. If life-threatening sequelae occur, or if fasting blood glucose remains ≥500 mg/dL (27.8 mmol/L) after 24 hours, medication should be permanently discontinued. If fasting blood glucose decreases to ≤500 mg/dL (27.8 mmol/L) within 24 hours, manage according to the hyperglycemia adjustment rules described above, based on the current blood glucose level.
Diarrhea
Grade 2 diarrhea: Discontinue medication until recovery to Grade 1 or below. If recovery occurs within 28 days, treatment can be restarted at the original dose or at a reduced dose level depending on clinical condition. If recovery takes longer than 28 days, treatment should be restarted at a reduced dose level. For recurrence of Grade 2 diarrhea, a reduced dose level is required.
Grade 3 diarrhea: Discontinue medication until recovery to Grade 1 or below. If recovery occurs within 28 days, treatment can be restarted at the original dose or at a reduced dose level depending on clinical condition. If recovery takes longer than 28 days, medication should be permanently discontinued.
Grade 4 diarrhea: Permanent discontinuation of medication.
Adverse Skin Reactions
Grade 2 Skin Reaction: Discontinue administration until recovery to Grade 1 or below. Resume treatment at the original dose after recovery. If a Grade 2 skin reaction persists or recurs, reduce the dose level by one.
Grade 3 Skin Reaction: Discontinue administration until recovery to Grade 1 or below. If recovery occurs within 28 days, treatment can be resumed at the original dose; if recovery takes longer than 28 days, reduce the dose level by one. If a Grade 3 skin reaction recurs, discontinue the medication permanently.
Grade 4 Skin Reaction: Discontinue the medication permanently.
Other Adverse Reactions
Grade 2 Adverse Reaction: Discontinue administration until recovery to Grade 1 or below. Resume treatment at the original dose after recovery.
Grade 3 Adverse Reaction: Discontinue administration until recovery to Grade 1 or below. If recovery occurs within 28 days, treatment can be resumed at the original dose; if recovery takes longer than 28 days, reduce the dose level by one.
Grade 4 Adverse Reaction: Discontinue the medication permanently.
Dosage Adjustment When Using Potent and Intermediate CYP4503A Inhibitors Concomitantly
Potent CYP4503A Inhibitors:
Concomitant use of potent CYP4503A inhibitors should be avoided. If unavoidable, the dosage should be adjusted to: 320 mg orally twice daily for 4 days, followed by a 3-day break. After discontinuing the potent CYP4503A inhibitor, allow 3-5 half-lives of the inhibitor before resuming the original dosage.
Intermediate CYP4503A Inhibitors:
When using intermediate CYP4503A inhibitors concomitantly, the dosage should be adjusted to: 320 mg orally twice daily for 4 days, followed by a 3-day break. After discontinuing the intermediate CYP4503A inhibitor, allow 3-5 half-lives of the inhibitor before resuming the original dosage.
