甲磺酸艾日布林注射液halavan

[Function and Indication].
Erizibulin Mesylate Injection halavan is used for the treatment of patients with metastatic breast cancer who have been treated with at least 2 chemotherapy regimens that include anthracycline or paclitaxel.

[Model and Specification
Injection 1mg/2mL

【Usage and Dosage
Erizibulin mesylate is dissolved in 5% ethanol aqueous solution by volume at a concentration of 0.5 g/mL, and the usual dose administered (in a course of 21 d) is: 1.4 mg/m2 on d 1 and d 8, administered intravenously over 2-5 min.

Clinical Studies
Phase I clinical study
Three phase I studies were conducted in patients with advanced solid tumours (e.g., colorectal, ovarian, uterine, renal, liver, lung, etc.) who had received chemotherapy. The first phase I clinical study reported by Synold et al. enrolled 40 patients, and 38 patients could be evaluated. Erizibulin mesylate was administered by intravenous drip on d 1, d 8, and d 15, with 28 d as one cycle of chemotherapy, and the maximum tolerated dose (MTD) was determined to be 1.4 mg-m. The second phase I clinical study reported by Tan et al. enrolled 21 patients, with a total of 1.4 mg-m. The second phase I clinical study reported by Tan et al. enrolled 21 patients. The second was a phase I clinical study of 21 patients by Tan et al, in which eribulin mesylate was administered in dose increments of 0.25, 0.5, 1, 2, 2.8, and 4 mg-m by intravenous infusion for 1 h every 21 d. The MTD was determined to be 2.0 mg-m. The third is a phase I clinical study of 32 patients with advanced solid tumours reported by Goel et al. The starting dose of eribulin mesylate was 0.25 mg-m, and the maximum dose was 1.4 mg-m, which was administered by intravenous infusion for 1 h on d 1, d 8, and d 15, with one cycle of chemotherapy over a 28-d period, and the MTD was determined to be 1.0 mg-m. The phase I study reported by Minami et al. in Japan enrolled 15 patients with advanced solid tumours and was administered as d 1, d 8 intravenously for 21 d in one cycle of chemotherapy, with a final recommended MTD of 1.4 mg-m in the phase II study.The most common adverse effects of treatment were neutropenia, fatigue, nausea and peripheral neuropathy.
Phase II clinical study
In 2009 Vahdat et al. reported the results of a phase II clinical study. The study was an open, single-arm clinical study that enrolled 103 patients with metastatic breast cancer who had received prior anthracycline and paclitaxel-based chemotherapy, with the specific regimen of administration of eribulin mesylate 1.4 mg-m , 2-5 min i.v., d 1, d 8, d 15, and 28 d as a cycle. Due to the development of neutropenia on d 15, the regimen was adjusted to d 1, d 8 i.v., for a 2l d cycle. Of the 87 patients whose efficacy could be evaluated, 10 (11.5%) had partial response (PR), 37 (42.5%) had stable disease (SD), and 36 (41.4%) had progressive disease (PD). The overall objective response rate (ORR) was 11.5% (95% CI: 5.7% -20.1%), and the clinical benefit rate (PR + SD over 6 months) was 17.2% (95% CI: 10.0% -26.8%). The median duration of response (MDR), median progression-free survival (mPFS) and median overall survival (mOS) were 171, 79 and 275 d, respectively. In 2010, Cortes et al. reported the results of a phase II clinical study, which was also an open, single-arm clinical study, enrolling 299 patients with locally advanced breast cancer or metastatic breast cancer who had received anthracycline, paclitaxel, and capecitabine-based chemotherapy, of whom 291 patients received a 1.4 mg-m 2-5 min dose of eribulin mesylate intravenously on d 1, d 8, and d 8, respectively, and the results of a phase II study in which the patients received a 1.4 mg-m 2-5 min dose of eribulin mesylate intravenously on d 1, d 8, and d 8, respectively. Intravenous injection, d 1, d 8, 21 d for one cycle. Of the 269 patients who could be evaluated for efficacy, 25 (9.3%) had PR, 125 (46.5%) had SD, and 116 (43.1%) had PD, with an ORR of 9.3% (95% CI: 6.1% -13.4%), and a clinical benefit rate (PR+SD over 6 months) of 17.1%, with an MDR of 4.1 months, an mPFS of 2.6 months, and an mOS of 10.4 months. MDR was 4.1 months, mPFS was 2.6 months, and mOS was 10.4 months.
In 2010, Iwata et al. reported the results of a phase II clinical study, which was also an open, single-arm clinical study, in which 80 evaluable patients with locally advanced breast cancer or metastatic mastalgia received a cycle of eribulin mesylate 1.4 mg-m, 2-5 rain intravenously on d l, d 8, and 21 d. The ORR was 21.3%, and the MDR was 4.1 months, the mPFS was 2.6 months, and the mOS was 10.4 months. Results ORR was 21.3% (95% CI: 12.9% -31.8%), CBR was 27.5% (95% CI: 18.1% -38.6%). mDR was 1 19 d, mPFS was 112 d and mOS was 331 d. The results were as follows.
Phase III clinical studies
Twelves et al. reported an inter-peripheral multicentre, parallel, controlled, phase III clinical study (EMBRACE study) in which patients with locally advanced breast cancer or metastatic mastalgia were randomised to the treatment group of acebutolol mesylate and the control group (with other single-agent chemotherapeutic treatments, endocrine therapies and biologic therapies, etc.), with 762 patients randomised into the treatment group and the control group according to the ratio of 2:1, with the treatment group (n=508) receiving acebutol mesylate and the control group receiving acebutol mesylate. The treatment group (n=508) received 1.4 mg-m methanesulfonate, 2-5 rain intravenous injection, d 1, d 8, 21 d cycle, the control group (n=254) received conventional treatment, 96% received chemotherapy, 4% received endocrine therapy. The results of the study showed that the overall survival of the acebutolol mesylate group was 13.1 months, and that of the control group was 10.6 months, with statistically significant differences between the two groups (P=0.04); the median progression-free survival of the acebutolol mesylate group was 3.7 months, and that of the control group was 2.2 months, with statistically significant differences between the two groups (P=0.14); the median progression-free survival of the two groups was 3.7 months, and that of the control group was 2.2 months, with statistically significant differences between the two groups (P=0.15). 14); the ORR of the two groups was 12% and 5%, respectively (P=0.002). This product is the first single-agent chemotherapeutic agent used for metastatic breast cancer patients to obtain an improvement in overall survival, based on the results of this study, this product is approved by the U.S. FDA for the treatment of metastatic breast cancer patients who have received at least 2 chemotherapeutic regimens (including anthracycline and paclitaxel chemotherapeutic agents). Another phase III clinical study of 1102 patients with locally advanced breast cancer or metastatic breast cancer is underway. The main objective of this study is to evaluate the improvement in quality of survival and the safety of controlled treatment with E13butrin Mesylate and Capecitabine.

[PRECAUTIONS
Eriobulin mesylate injection was developed by Eisai (Eisa), Japan, and is the 1st single-agent chemotherapeutic agent used to obtain overall survival improvement in patients with metastatic breast cancer. Clinical studies of Eriobulin mesylate alone or in combination with other chemotherapeutic agents for the treatment of various types of cancers, including bladder, prostate, pancreatic, head and neck, and non-small-cell lung cancers, etc., are ongoing, and the subsequent treatment of metastatic breast cancer is being evaluated. international multi-centre Phase III clinical study is also underway. Erizibulin mesylate for the treatment of metastatic breast cancer is very significant, and the later development of a wide range of indications, it is a very valuable application of the drug.

[Adverse Reactions and Contraindications
The results of several phase I clinical studies have shown that neutropenia is one of the most common dose-limiting toxicities of the product, with the incidence increasing from 22 per cent (at a dose of 1.4 mg-m ) to 100 per cent (at the maximum administered dose of 4 mg-m ).The most common adverse reaction reported in the phase I clinical studies by Goel et al. was fatigue (53 per cent ), followed by nausea (41 per cent) and anorexia ( 38%).The most common adverse reactions reported by Tan et al. in their phase I clinical study were neutropenia (38%, 33% grade 3-4), fatigue (33%, all grade 1-2) and alopecia (33%, all grade 1-2).The most common grade 3-4 adverse reactions in the treatment of azbutolol mesylate as reported by Vahdat et al. in their phase II clinical study were in the order of neutropenia (64%), leukopenia (18% ), fatigue (5%), peripheral neuropathy (5%), and febrile neutropenia (5%).The results of the phase II clinical study reported by Cortes et al. showed that the most common grade 3-4 adverse reactions in the treatment of this product were neutropenia (54%), leukopenia (14%), fatigue and weakness ( 10%), etc. In the phase III clinical study (EMBRACE study), the majority of adverse reactions were grade 1-2, except for neutropenia, which was grade 3-4, and the incidence of neutropenia was 21.1 per cent for grade 3 and 24.1 per cent for grade 4. Peripheral neuropathy grade 3 is 7.8%, grade 4 is 0.4%.

Drug interactions
The results of preclinical pharmacokinetic study showed that Erizibulin mesylate has a rapid distribution phase and a long elimination phase, with a mean elimination half-life of about 40 h. Its in vivo drug area under the drug-time curve (AUC) and peak blood concentration (Cmax ) are linearly proportional to the dose. The steady-state volume of distribution of the drug is 43-114 L/m2 , and plasma clearance is 1.16-2.42 L-h-1-m-2 , with slower elimination. Although it has been shown that Erizibulin mesylate is metabolised by CYP3A4, it does not affect other drugs metabolised by CYP3A4, such as carbamazepine, diazepam, paclitaxel, etc .

Storage
Store at room temperature away from light.

Manufacturer
Developed by Eisai (Eisa), Japan.