Approval date: October 19, 2010
Modification date: 09/03/2015
Modification date: 09/06/2017
Date of modification.
Tegeo capsules instructions
Please read this instruction manual carefully and use under the guidance of a physician
【Drug name】.
Generic name: Tegeo capsules
English name: Tegafur, Gimeracil and Oteracil Potassium Capsules
Hanyu Pinyin: Tiji’ ao Jiaonang
Ingredients
This product is a compound preparation, each capsule contains.
20mg: Tegafur 20mg, Gimeracil 5.8mg, Oteracil Potassium 19.6mg.
Specification of 25mg: Tegafur 25mg, Gimeprazine 7.25mg, Otilacid Potassium 24.5mg.
Properties
This product is a capsule, the content of white or off-white granules or powder.
Indications
Unresectable locally advanced or metastatic gastric cancer.
Specification
(1) 20mg (based on tegafur) (2) 25mg (based on tegafur)
Dosage and Administration
Dosage.
Tegeo capsules are used in combination with cisplatin for the treatment of unresectable locally advanced or metastatic gastric cancer.
In general, the first dose for adults is determined according to the body surface area according to the table below. The dose is administered orally twice daily, after breakfast and dinner, for 28 consecutive days with a 14-day break for one treatment cycle. The dose is administered until the patient’s condition deteriorates or becomes intolerable.
Body surface area (m2) Initial dose (based on tegafur) <1.25 40mg per dose ≥1.25 to <1.5 50mg per dose ≥1.5 60mg per dose Dosing may be increased or decreased according to the patient’s condition. Each dose is administered in increasing or decreasing order in four dose classes of 40mg, 50mg, 60mg, and 75mg. If there are no safety concerns such as abnormal laboratory tests (blood tests, liver and kidney function) or gastrointestinal symptoms caused by the drug, and if the physician determines that an increase is necessary, the dose may be increased by one dose level in the above order, up to 75mg/dose. If a dose reduction is required, the dose will be reduced in accordance with the dose class, with a lower limit of 40mg/dose. Cisplatin is administered orally for 21 consecutive days, with a 14-day break and an intravenous drip of 60 mg/m2 on day 8 of dosing for one treatment cycle. Administer until the patient’s condition deteriorates or becomes intolerable.
Precautions for dosing.
Dosing may be increased or decreased according to the patient’s condition by referring to the following criteria
Decrease first dose increment stop each 40mg each 50mg stop ← each 40mg each 50mg each 60mg stop ← each 40mg each 50mg each 60mg each 75mg increment should not exceed one dose level per cycle. 2.
2. If the chemotherapy interval needs to be shortened, safety issues such as abnormal laboratory tests (blood count, liver and kidney function) and gastrointestinal symptoms caused by this drug must be confirmed, but the chemotherapy interval should not be less than 7 days. The safety of shortening the chemotherapy interval in patients with inoperable or recurrent breast cancer has not been confirmed (no clinical experience with the drug). To avoid serious adverse effects such as myelosuppression and fulminant hepatitis, laboratory tests (routine blood and liver and kidney functions) and comprehensive observation of the patient’s condition must be performed before the start of each chemotherapy treatment, and at least once every 2 weeks during chemotherapy. If any abnormalities are found, appropriate measures must be taken, such as prolonging the chemotherapy interval, reducing the dose or stopping the drug as specified above. The first treatment cycle or increase in dose must be more closely observed and examined. 4. Basic studies (rats) have found that fasting changes the bioavailability of octreotide potassium, resulting in a weakened inhibition of fluorouracil phosphorylation, thus reducing the antitumor effect of the drug.
Precautions for patient use.
Patients should be aware of the following when administering the drug.
This drug is packaged in an aluminum-plastic blister (PTP) and patients should be informed that they need to press the drug out of the blister before taking the drug. There have been reports of patients accidentally taking aluminum foil plates, resulting in esophageal perforation and serious complications such as mediastinitis.
[Adverse reactions].
Foreign clinical trials
1. Combination therapy
A multicenter phase III randomized controlled trial comparing Tegeo capsules alone (Tegeo capsules 40-60 mg/dose orally twice daily for 28 consecutive days with a 14-day break) and Tegeo capsules combined with cisplatin (Tegeo capsules 40-60 mg/dose orally twice daily for 21 consecutive days with 60 mg/m2 cisplatin on day 8) in patients with advanced gastric cancer was conducted in Japan. The major adverse reactions of 298 patients who could be evaluated for adverse reactions in a multicenter phase III randomized controlled trial of treatment are shown in the table below.
Incidence of adverse reactions Monotherapy group (n=150) Combination therapy group (n=148) Leukopenia (CTC≥3 degree #1) 38% (2%) 70% (11%) Neutropenia (CTC≥3 degree) 42% (11%) 74% (40%) Anemia (CTC≥3 degree) 33% (4%) 68% (26%) Thrombocytopenia (CTC≥3 degree) 18% (0%) 49% (5%) Loss of appetite (CTC ≥ 3 degrees) 37% (6%) 72% (30%) Nausea (CTC ≥ 3 degrees) 26% (1%) 67% (11%) Vomiting (CTC ≥ 3 degrees) 14% (2%) 36% (4%) Stomatitis (CTC ≥ 3 degrees) 21% (0%) 29% (0.7%) Diarrhea (CTC ≥ 3 degrees) 23% (3%)34% (4%)Weakness (CTC≥3 degrees)33% (1%)57% (4%)Hyperpigmentation (CTC≥3 degrees)40% (0%)36% (0%)Rash (CTC≥3 degrees)19% (1%)22% (2%)Overflowing tears (CTC≥3 degrees)16% (0.7%)18% (0%)#1 Common Toxicity Determination by National Cancer Institute Criteria (NCI CTCAE) grading.
The late phase II clinical trial of combination chemotherapy for non-small cell lung cancer (21 consecutive days of oral tegeo capsules with 60 mg/m2 cisplatin given at day 8) found that all 55 patients evaluable for adverse reactions experienced adverse reactions, and the major adverse reactions are shown in the table below.
Incidence of adverse reactions combination therapy non-small cell lung cancer patients (55 patients)#2100.0% (61.8%)Leukopenia (<2000/mm3) 52.7% (5.5%)Neutropenia (<1000/mm3) 65.5% (29.1%)Hemoglobin reduction (<8g/dL) 90.9% (21.8%)Thrombocytopenia (<5×104/mm3)60.0% (1.8%)Aspartate aminotransferase (AST) elevation 14.5%Alanine aminotransferase (ALT) elevation 14.5%Loss of appetite (CTC ≥3 degrees)78.2% (12.7%)Nausea (CTC ≥3 degrees)65.5% (10.9% ) Vomiting (CTC ≥ 3 degrees) 38.2% (7.3%) Diarrhea (CTC ≥ 3 degrees) 34.5% (7.3%) Stomatitis 25.5% Hyperpigmentation 23.6% Skin rash 9.1%
#2: Graded according to the National Cancer Institute Common Toxicity Criteria for Adjudication (NCI CTCAE).
2. Monotherapy
Of the 578 patients who could be evaluated for adverse reactions (excluding previously treated breast, pancreatic, and bile duct cancer patients described below), the incidence of adverse reactions was 87.2% (504 patients). The incidence of adverse reactions was higher in patients with inoperable or recurrent breast, pancreatic, and bile duct cancers treated with paclitaxel previously compared with other types of tumors, 96.4%, 98.3%, and 94.9%, respectively. The incidence of adverse reactions was higher in patients with pancreatic cancer, and gastrointestinal reactions such as loss of appetite, nausea, vomiting and diarrhea were particularly pronounced. The following adverse reactions are common when used as monotherapy.
Adverse reactions monotherapy all patients
(578 cases) #3 previously treated breast cancer patients
(55 patients) with pancreatic cancer
(59) Patients with bile duct cancer
(59 cases)#3 patients with gastric cancer
(134 cases) Incidence
(CTC ≥3 degrees)#487.2%
(22.5%) 77.6%
(20.9%)96.4%
(30.9%)98.3%
(42.4%)94.9%
(30.5%)Leukopenia (<2000/mm3)45.8%
(2.8%)48.5%
(3.7%)69.1%
(9.1%)32.2%
(0%)49.2%
(3.4%) Neutropenia
(<1000/mm3) 43.9%
(8.5%)47.8%
(7.5%)72.7%
(10.9%)27.1%
(6.8%)42.4%
(5.1%) Hemoglobin reduction (<8g/dL) 38.1%
(5.7%)38.8%
(7.5%)45.5%
(3.6%)50.8%
(5.1%)50.8%
(6.8%)Thrombocytopenia
(<5×104/mm3)10.9%
(1.6%)9.0%
(1.5%)38.2%
(1.8%)33.9%
(1.7%)23.7%
(0%) Elevated AST (GOT) 11.1% 4.5% 34.5% 18.6% 37.3% Elevated ALT (GPT) 11.1% 3.7% 29.1% 16.9% 27.1% Loss of appetite
(CTC ≥3 degrees) 33.9%
(3.5%)22.4%
(2.2%)54.5%
(5.5%)61.0%
(13.6%)33.9%
(6.8%) Nausea
(CTC ≥3 degrees) 22.3%
(0%) 9.7%
(0%)47.3%
(0%)55.9%
(10.2%)32.2%
(3.4%) Vomiting
(CTC ≥3 degrees) 7.8%
(0.5%) 2.2%
(0%) 30.9%
(0%) 35.6%
(5.1%) 20.3%
(1.7%) Diarrhea
(CTC ≥3 degrees) 18.7%
(2.9%) 12.7%
(3.0%) 38.2%
(5.5%) 37.3%
(6.8%) 22.0%
(1.7%) General discomfort #522.3%11.9%47.3%47.5%35.6% Stomatitis 17.1%11.2%41.8%25.4%27.1% Hyperpigmentation 21.3%18.7%47.3%39.0%42.4% Rash 11.8%9.7%16.4%22.0%22.0%
#3: Includes phase II multicenter registration clinical trials conducted in Japan in gastric, colorectal, non-small cell lung, head and neck, and breast cancers; excludes patients with previously treated breast, pancreatic, and bile duct cancers.
#4: Use the National Cancer Institute Common Toxicity Criteria for Adjudication (NCI CTCAE) or the Japanese Society of Clinical Oncology classification.
#5: Includes malaise.
3. Time to onset of adverse reactions and recovery time
The time to onset of adverse reactions in 453 patients enrolled in phase II clinical trials of tegeo capsules for the treatment of gastric, colorectal, head and neck, non-small cell lung cancer (monotherapy), inoperable or recurrent breast cancer, pancreatic cancer, and bile duct cancer were analyzed as follows.
The median time required from the start of drug administration to the lowest values of white blood cell count <3000/mm3, hemoglobin <8g/dL, and platelet count <7.5×104/mm3 throughout the cycle was 27, 25, and 24 days, respect