肺癌

Some Chinese Avastin prescribing information (for reference only)
Bevacizumab / Avastin / Bevacizumab, a single antigen-origin English trade name: Avastin Avastin
Origin of the English drug name: bevacizumab BEVACIZUMAB
English translation of information goods: Awas Tinga Avastin
Elements of the structure name: bevacizumab
Avastin Bevacizumab (trade name Avastin) English Manual
【Properties】
Formulations: agent. Dose: Two, 100mg/4ml, or 400mg/16ml.
Of Clinical Pharmacology mechanism of action 【】
Bevacizumab (trade name Avastin) is a recombinant human IgG1 monoclonal antibody, by inhibiting the human vascular endothelial growth factor biological activity of the work.
That Avastin can be combined with VEGF and to prevent endothelial cell surface receptors (Flt-1 and KDR) binding. In vitro model of angiogenesis, VEGF and their corresponding receptors may lead to endothelial cell proliferation and angiogenesis. Vaccination of colon cancer in nude (athymic) mouse model, the use of Avastin to reduce angiogenesis and inhibit the transfer of disease progression.
Pharmacokinetics】
Avastin pharmacokinetic curve, only detect the total concentration of serum (ie, Avastin does not differentiate between free and integrated into the VEGF ligands Avastin). Based on a certain population pharmacokinetic analysis: 491 patients receiving 1 ~ 20mg/Kg Avastin week, a second, every 2 weeks a second, or every 3 weeks one time, it is estimated half-life of Avastin is approximately 20 days (range 11 to 50 days). The time to reach steady-state is expected to 100 days. Using a dose of 10 mg / kg, every 2 weeks a meeting of the Avastin treatment, the serum accumulation ratio was 2.8. Avastin in patients with serum removal and body weight, gender, and tumor burden vary.
After the adoption of body weight than are men than women have a higher clearance rate (0.262 liters / day right. 0.207 liters / day) and a larger clearance volume (3.25 liters of 2.66 liters). A large tumor burden (greater than or equal to the median value of tumor surface area) than the tumor burden in patients with small (less than the median value of tumor surface area) patients have a higher clearance rate (0.249 liters / day for 0.199 liters / day) . 813 patients were enrolled in a clinical randomized experimental study, there was no evidence in the application of Avastin, the tumor burden in relation to women and small patients, male or a large tumor burden in patients with poor efficacy. Avastin clinical efficacy and the relationship between exposure has not yet conclusive.
【Special population】
Demographic analysis of data suggest that: No because the patient's age or gender make dose adjustments.
In patients with impaired renal function: There is no Avastin in patients with renal impairment the pharmacokinetics study.
In patients with liver failure: There is no Avastin in patients with liver insufficiency pharmacokinetic study.
Clinical Research 【】
There are two randomized clinical studies used to evaluate Avastin combined with 5-Fu-based chemotherapy in the treatment of metastatic colorectal cancer efficacy and safety. Avastin combined intravenous bolus IFL program. Study 1 is a double-blind, randomized clinical study for evaluating Avastin as first-line treatment of metastatic colorectal cancer. Patients were randomly assigned to three groups: one group + placebo bolus IFL (irinotecan 125 mg/m2 bolus, 5 - fluorouracil 500 mg/m2 bolus, leucovorin 20 mg/m2 bolus, weekly 1 qd for 4 weeks, 6 weeks of a cycle); Group 2 bolus IFL + Avastin (5 mg / kg every 2 weeks one time); Group 3 to 5-FU / LV + Avastin (5 mg / kg every 2 weeks one times).
Pre-determined, when the bolus IFL + Avastin toxicity of the program has been evaluated as acceptable, the first three groups into the group is suspended. 813 patients were randomly assigned to group 1 and group 2, the median age was 60 years old, 40% were female, 79% were Caucasian, 57% of patients with ECOG score of 0 points, 21% primary in the rectum, 28% received adjuvant chemotherapy, 56% of patients with primary lesions in the ventrolateral, 38% of patients with primary lesions in the liver. The study of the characteristics of patients between groups is basically similar.
The two main experimental group also according to their age, gender, race, ECOG score, primary tumor site, whether it had received adjuvant therapy, the transfer of the site and size of tumor burden is divided into different sub-groups to evaluate their acceptance of Avastin The clinical benefit rate.
In Group 3 of 110 patients, the median survival was 18.3 months, median progression-free survival was 8.8 months, overall response rate was 39%, with a median response duration was 8.5 months.
A joint study with the 5-FU/LV Avastin 2 is a randomized study of a clinical study to evaluate Avastin combined with 5-FU/LV as first-line metastatic colorectal cancer treatment. Patients were randomly assigned to three groups, group 1 to accept the simple 5-FU/LV regimen (5 - fluorouracil 500 mg/m2, leucovorin 500 mg/m2 weekly 1 qd for 6 weeks , 8-week cycle 1); Group 2 5-FU/LV chemotherapy plus Avastin 5 mg / kg every 2 weeks a second;) Group 3 for the 5-FU/LV chemotherapy plus Avastin 10mg / kg every 2 weeks one time; patient to receive treatment until disease progression. The primary endpoint of the study is efficient and progression-free survival
Receiving 5-FU/LV + Avastin 5 mg / kg treatment group was the period of progression-free survival significantly better in the treatment group did not receive Avastin. However, in the overall survival period and the total efficiency, between the two groups no significant difference. Accept 5-FU/LV + Avastin 10 mg / kg treatment group did not receive Avastin with the efficacy of the treatment group did not differ significantly.
Avastin monotherapy 【】
At present, there is no Avastin monotherapy efficacy in colorectal cancer results. However, there is an ongoing randomized study, in the acceptance of 5 - fluorouracil + irinotecan-based chemotherapy is still the progress of metastatic colorectal cancer patients given single-agent Avastin treatment, but this study due to a single agent in Avastin treatment efficacy and survival than the acceptance of 5 - fluorouracil + leucovorin + oxaliplatin FOLFOX program for the poor was suspended.
【Warning】
Gastrointestinal perforation / wound healing complications (see "DOSAGE AND ADMINISTRATION: Dose Adjustment")
Gastrointestinal perforation / wound healing complications associated with intra-abdominal abscess, compared with the control patients receiving Avastin have a higher incidence. In pre-clinical animal models, Avastin may affect wound healing.
In the study 1, IFL + placebo group, 396 patients had one (0.3%), IFL + Avastin group, 392 patients with 6 (2%) ,5-FU / LV + Avastin group in, 109 patients were four (4%), gastrointestinal perforation, and some even fatal, these complications can be with or without intra-abdominal abscess, and may occur at any time during treatment. According to reports, the typical performance is abdominal pain, accompanied by a number of symptoms such as constipation or vomiting.
In addition, IFL + placebo group, 396 patients were 2 (0.5%), IFL + Avastin group, 392 patients with four (1%) ,5-FU / LV + Avastin group, 109 patients had one (1%) in the treatment of the wound occurs during cracking. An interval after the operation over a long time to start Avastin treatment in order to avoid the impact of wound healing, is still inconclusive. In Study 1, research programs are not allowed within 28 days after surgery in patients with the use of Avastin. 1 patients (study a total of 501 patients receiving AVASTIN), in more than two months after receiving the Avastin treatment, there anastomotic cracking.
Similarly, in order to avoid the impact of Avastin treatment of wound healing, in the Avastin treatment long after the end of an interval of further elective surgery, has not yet conclusive. 1,190 in the study received IFL + Avastin-treated patients, 39 patients in Avastin underwent surgery after treatment in these patients, there are six (15%) had wound healing / bleeding complications.
In the same study, 193 patients receiving IFL, there are 25 patients in the treatment received after the end of surgery in these patients, only one (4%) had wound healing / bleeding complications. The end of treatment and the emergence of the longest interval of wound cracking appears in the receiving IFL + Avastin treated patients, the interval time is 56 days. After treatment in the Avastin and subsequent elective surgery to consider the time interval between the half-life of Avastin (approximately 20 days). If the application of Avastin in patients appear in the course of gastrointestinal perforation or wound dehiscence requiring medical intervention, that Avastin will be permanently disabled.
Bleeding (see "DOSAGE AND ADMINISTRATION: Dose Adjustment").
In patients receiving Avastin, the existence of two different bleeding. The most common are mild bleeding, mainly as a nasal hemorrhage; the first two kinds of situation as serious and sometimes fatal bleeding. Severe bleeding events first appeared in the treatment of non-small cell lung cancer patients, which suggests Avastin should not be approved for the treatment of non-small cell lung cancer.
There is a non-small cell lung cancer clinical research, patients were randomly assigned to chemotherapy with or without Qaa Wa Siting treatment, 13 received chemotherapy in the treatment of squamous cell carcinoma Qaa Wa Siting of 4 (31%) and 53 undergoing chemotherapy treatment for non-Wa Siting Qaa squamous cell carcinoma in 2 (4%) had bronchial threatens the life or fatal bleeding, and in the chemotherapy group, 32 patients and no case occurred (0%).
Fatal bleeding in these patients, there are many receiving Avastin treatment or treatment before the tumor appeared empty or necrosis. These serious bleeding occur very suddenly, showed hemoptysis. There is no regard to the transfer of the central nervous system in patients receiving AVASTIN occurs when the central nervous system evaluation of the risk of bleeding, as in this study, funded by Genentech, there is the transfer of the central nervous system associated with central nervous system bleeding In one study, were excluded. There are some reports in the receiving AVASTIN had taken place in some of the less frequent serious bleeding, including gastrointestinal bleeding, subarachnoid hemorrhage and hemorrhagic shock.
If there is need for medical intervention in patients with severe bleeding, Avastin should be suspended immediately and give a positive medical treatment. Recent bleeding in patients receiving AVASTIN should be.
a including one or more systolic or diastolic pressure exceeded the standard value of
In the Avastin treatment group occurred in patients with severe hypertension, there are slightly more than half (51%) of patients with diastolic blood pressure over 110, while the systolic blood pressure less than 200. Of receiving AVASTIN in patients with hypertension occurred three made medical treatment including the use of angiotensin-converting enzyme inhibitors, β-inhibitors, diuretics, calcium channel blocker.
In the out 4 months after treatment, 26 received IFL + Avastin treatment 18, 10 receiving IFL + placebo in the 8 are still persistent high blood pressure. In all clinical studies (n = 1032), there are 17 patients with hypertension or high blood pressure increase required hospitalization or disable the Avastin treatment. This is 17 there are four appeared hypertensive encephalopathy. There is a severe hypertension complicated by a subarachnoid hemorrhage.
In the event of hypertensive crisis in patients with Avastin to be a long-term disabled. In the medical treatment without the control of severe high blood pressure, it is recommended Avastin should be suspended.
Proteinuria (See: "DOSAGE AND ADMINISTRATION: Dose Adjustment")
In Study 1, compared with IFL + placebo, receiving IFL + Avastin treated patients, proteinuria (urine protein as the + or higher) the incidence and severity are increasing. IFL + placebo group, 14% of patients had proteinuria of + + or higher, IFL + Avastin treatment group, 17% of patients ,5-FU / LV Avastin treatment group, 28% of patients. Collection of new or increased proteinuria in patients with a 24-hour urine, 158 patients receiving IFL + Avastin treatment there are three (2%), 50 patients receiving 5-FU/LV + Avastin treatment there were 2 (4 %) of 3 proteinuria (according to the U.S. National Cancer Institute toxicity criteria, namely, a 24-hour urine protein> 3.5 g).
In a different doses of Avastin, placebo-controlled treatment of renal cell carcinoma randomized controlled study, that is because of this situation not been approved. Approximately half of the subjects collected a 24-hour urine, in these persons, 19 receiving Avastin (10 mg / kg, 2 weeks 1 times) in subjects treated with 4 (21%), 14 receiving Avastin (3 mg / kg, 2 weeks 1 times) in the treatment of the subjects have two people (14%) occurred 3 proteinuria (24-hour urine protein> 3.5 g).
The 15 subjects, placebo-controlled, none appeared. In the Genentech company-sponsored this study, 1032 subjects had 5 (0.5%) had nephrotic syndrome. Of these, one person died, a people who need dialysis, while 3 out Avastin in a few months later proteinuria remains a serious anomaly, with no proteinuria in the disabled back to normal after treatment Avastin.
Patients with nephrotic syndrome, Avastin should be suspended. Proteinuria in patients with moderate to severe safety of the use of Avastin is currently not yet conclusive. But in most clinical studies, when a 24-hour proteinuria ≥ 2 g, that is to disable Avastin, if the 24-hour proteinuria <2 g, according to a 24-hour urine in patients diagnosed with moderate to severe proteinuria should be regular monitoring, until the situation worse or better before deciding whether to disable the Avastin.
Congestive heart failure 【】
Congestive heart failure, according to the U.S. National Cancer Institute toxicity criteria ranged from 2 to 4 left ventricular dysfunction. In the study funded by Genentech Inc., according to reports, 1032 subjects received treatment with Avastin and 5 (2%), congestive heart failure occurred.
44 At the same time receiving Avastin and anthracycline therapy, there are 6 subjects (14%) occurred in the 299 had received anthracycline or left chest wall radiation therapy of the subjects there are 13 ( 4%) occurred. In another controlled study, patients receiving Avastin plus chemotherapy group the incidence of congestive heart failure is higher than group receiving chemotherapy alone. Avastin in patients with cardiac dysfunction begun using the safety of the treatment not in the study.
【Note】
Overview
Avastin or its products on any one component should be used with caution in patients with allergy.
【Infusion reaction】
Application of the first dose of Avastin infusion reactions occur is not common ( "3%). There are two patients with serious infusion reactions. The first application of a person when wheezing, shortness of breath.
Another patient in the use of Taxol with Avastin, when follow-up occurred three allergic reactions and required hospitalization for treatment. The use of Avastin in their third, two patients were on the use of effective medical treatment, there is no follow-up information. When severe infusion reactions, Avastin should be suspended and appropriate medical attention. There is no information on what kind of methods that can identify those who had a serious infusion reactions occurred in those who re-used if it is safe.
【Operation】
Should at least 28 days after starting Avastin treatment. At the beginning of Avastin treatment, surgical incision should be fully healed. Because Avastin influential wound healing potentially dangerous. In elective surgery, they should suspend the Avastin treatment.
Avastin is not known the last time an interval between surgical treatment and how long it is appropriate, however, the estimated half-life of Avastin is 20 days (see CLINICAL PHARMACOLOGY: Pharmacokinetics), interval of drug should be considered The half-life. (See the warning: "gastrointestinal perforation / wound healing complications")
【Cardiovascular disease】
If the patient in the treatment of the previous year there had been more serious cardiovascular disease, will be excluded from the clinical study of Avastin in addition. Therefore, it is more severe in patients with cardiovascular disease safety of Avastin has not been fully evaluated.
Immunogenicity 【】
As a therapeutic protein, there must be a potential immunogenicity. In patients receiving Avastin in the incidence of antibodies is still not fully conclusions. Because the inspection methods for detecting low titer antibodies do not have enough sensitivity. 500 receiving Avastin treatment (mainly and chemotherapy combined) in serum, using enzyme-linked immunosorbent assay testing, there is no resistance to high titer antibody Avastin there.
Since the immunogenicity of the data is highly dependent on the sensitivity and specificity of detection methods, but also to detect the positive rate is also affected by a variety of factors, including sample handling, sample collection time, at the same time of treatment and potential diseases. For these reasons, may have misled the Avastin antibody incidence and the incidence of other substances antibody results of the comparison.
【Laboratory tests】
In the patients receiving Avastin treatment, every 2 to 3 weeks should monitor their blood pressure. If there should be more frequent in patients with hypertension to monitor their blood pressure. Since receiving Avastin treatment induced or exacerbated by high blood pressure and withdrawal of patients should continue to regularly monitor their blood pressure.
Patients receiving AVASTIN should be systematic urine checks to monitor whether the induced or aggravated proteinuria. Patients with 2 + proteinuria or more severe should check the 24-hour urine to do further evaluation. (See the warning: "Proteinuria and DOSAGE AND ADMINISTRATION: Dose Adjustment")
【Drug interactions】
Avastin is currently not carried out with the formal study of interaction between anticancer drugs. In Study 1, patients given irinotecan / 5-FU/CF (bolus IFL) combined with or without AVASTIN.
In the bolus IFL alone and in combination with AVASTIN when the concentration of irinotecan are the same. However, IFL co-Avastin patients in the irinotecan active metabolite SN38 concentration bolus IFL alone group than in patients with an average of 33%. In Study 1, bolus IFL in combination with AVASTIN have occurred where 3 ~ 4 diarrhea and neutropenia to reduce the incidence of high, but into the group of patients because of the diversity and the limited nature of the sample, Avastin combined irinotecan SN38 caused by elevated levels of the degree of influence is unclear.
Carcinogenicity, mutagenicity and fertility damage. Avastin is currently no information on human and animal carcinogenicity data. Avastin could damage fertility. By 10 or 50mg/kg dose of Avastin to give female macaque 13 consecutive or 26 weeks after the discovery of ovarian and uterine weight, endometrial proliferation, reduce the number of menstrual cycles, as well as block follicular development and luteal missing a dose-related .
Withdrawal and to give four to 12 weeks of recovery time, in the high-dose group were examined, the group plans to resume the inspection of the two female macaque results suggest that the damage is reversible. After the 12-week recovery period, follicular development block away, but there is still moderate degree of ovarian weight reduction, reduction in the proliferation of endometrial disappeared, but the uterine weight reduction is still significant, two macaque, there is still a yellow body loss and reduce the number of menstrual cycles (67%).
【Pregnancy】
To mg / kg as a unit, if he is given two times the recommended dose in rabbits Avastin will produce deformity. Observed effects include reduction in maternal and fetal weight, fetal abortion increased and fetal body and an increase in the incidence of skeletal changes. All dose groups were observed on the fetus.
Angiogenesis of fetal development is essential. Receiving AVASTIN-induced angiogenesis is inhibited may be the cause of pregnancy side effects causes. However, Avastin's impact on pregnant women, there are no adequate and well-controlled clinical study. Only by fully weigh the potential risk to the fetus Avastin, when in order for pregnant women and failed to take appropriate contraceptive measures, women's access to its treatment. All patients should be informed before the start of treatment Avastin's potential risk to the fetus.
If the course of treatment in patients receiving Avastin in pregnant, she should be informed Avastin harm the fetus and abortion of potentially dangerous. Even the withdrawal of the patient, she shall be informed of the follow-up of residual withdrawal (Avastin half-life of approximately 20 days) and its possible impact fetal development.
Lactating mothers 【】
It is not known whether AVASTIN is secreted into human milk. As the people IgG1 is secreted into human milk, so it may be due to its uptake and absorption of fetal harm caused by unknown. Therefore, receiving Avastin treatment and follow-up of the residual time, taking into account the half-life of the product, about 20 days (range 11 ~ 50 days), this period of time should stop breast-feeding.
(See Clinical Pharmacology: Pharmacokinetics)
Use】 【children
There were no patients on Avastin in pediatric safety and efficacy studies. However, in young macaque, using less than the recommended dose (in mg / kg as a unit) of Avastin 4 weeks later, observed stunted. Dysplasia the incidence and severity are dose-related, but at least part of the cessation of treatment, they could be restored.
【Use of the elderly】
In Study 1, (according to the U.S. National Cancer Institute toxicity criteria) occurred 3 to 4 the number of side effects, including all subjects (396 IFL + placebo, 392 IFL + Avastin, 109 5-FU / LV + Avastin). But the side effects occurred 1 to 2 the number of people included only 309 sub-groups of subjects.
Therefore not collected enough side-effects occurred 1 to 4 patients ≧ 65 years of age the number of samples to prove that the general side-effects occurred in elderly patients and young patients the situation is different. 392 received IFL + Avastin treated patients, there are 126 ≧ 65-year-old, these patients asthenia, sepsis, deep thrombophlebitis, hypertension, hypotension, myocardial infarction, congestive heart failure, diarrhea, constipation, loss of appetite subside, leukopenia, anemia, dehydration, hypokalemia, hyponatremia incidence of side effects than the "65-year-old patients with a high. In the overall survival period, the efficacy of Avastin in the elderly group and younger group the same.
In the income group to help Genentech funded clinical study of 742 patients recorded all the side effects occurred. Of which 212 (29%) were aged ≧ 65 years, more 43 (6%) were aged ≧ 75 years of age. Any level of side effects, in the elderly group than those in the younger group of high incidence, as described above, there are dyspepsia, gastrointestinal hemorrhage, edema, epistaxis, increased cough, and voice changes.
【Side effects】
With Avastin The most serious side effects include:
Gastrointestinal perforation / wound cracking syndrome (see warning)
Bleeding (see warning)
Hypertensive crisis (see warning)
Nephrotic syndrome (see warning)
Congestive heart failure (see warning)
In 1032 into the group of Genentech-funded clinical research and treatment of patients receiving Avastin, the most common serious side effects are: anemia, pain, high blood pressure, diarrhea and leukopenia.
In the 742 into the clinical research group funded by Genentech, and receiving Avastin-treated patients, at all levels of the most common side effects are: anemia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, loss of appetite , stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis and proteinuria.
Because clinical trials there are many different conditions, so in the experiment observed the incidence of side effects of certain drugs can not be another incidence of side effects of drugs to do a direct comparison. The clinical trials, the side effects of the information obtained as well. However, you can identify as the incidence of drug-related side effects and their basis.
A total of 1032 patients (568 metastatic colorectal cancer and 473 other cancers) into the clinical research group funded by Genentech and received Avastin treatment alone, 157 drug treatment, with chemotherapy combined with a 875. Except for 290 of these 742 patients have to collect all the side effects, all (NCI-CTC) 3,4-level side effects are collected, while the 1,2-level side effects (such as hypertension, proteinuria, and thrombotic events) have a choice nature of the collection.
Genentech-funded clinical studies collected in the side-effects will be used in future for further identification of specific side effects. (See Warning: hemorrhage, hypertension, proteinuria, congestive heart failure and attention: older applications.) Side-effects of contrast, there are currently limited to research 1, a 897 involved in the treatment of patients with metastatic colorectal cancer randomized研究.
Place where the staff all the 3,4-level side effects and have a choice of some 1,2-level side-effects (hypertension, proteinuria, thromboembolic events) were reported. In Study 1, the median age was 60 years old, male 60%, 78% of the primary in the colon, 29% received assistance or neo-adjuvant chemotherapy. Study 1, group 2 Avastin The median exposure time was 8 months, group 3 was 7 months. In a 309 sub-group, all of the side effects, including the 1,2-level side-effects (NCI-CTC) were reported. The safety of 309 sub-groups into the group of standards with the entire study into the group of standards is the same, and the three research team have a good balance. Serious or threatens life (NCI-CTC3, 4 level) side effects, in the bolus IFL + Avastin group rate (2%) compared with bolus IFL + placebo. Table 4:
【Skin and mucous membrane bleeding】
In Study 1, patients receiving Avastin serious or non-occurrence rates of serious bleeding was higher (see Warning: bleeding). 309 took place in the collection of a ~ 4 patients with bleeding, nose bleeding is relatively common, IFL + Avastin group incidence of 35%, while the IFL + placebo group the incidence rate was only 10%. Such side effects are generally very light (NCI-CTC1 level), without dealing with can be resumed. Some light to moderate incidence of side effects of IFL + Avastin group was higher than IFL + placebo groups, including gastrointestinal bleeding (24% vs. 518 6%), minor gum bleeding (2% vs. 0) and vaginal bleeding (4% vs.2%).
【】 Thromboembolism
In the study of 1,18% of the IFL + Avastin patients and 15% of the IFL + placebo group of patients with grade 3-4 thromboembolic events. Level in the following 3-4 thromboembolism incidence IFL + Avastin group was higher than IFL + placebo group, cerebral vascular events (4 vs. 0 patients), myocardial infarction (6 vs. 3), deep venous thrombosis (34 vs . 19), intra-abdominal thrombosis (13 vs. 5). The contrast is that the incidence of pulmonary embolism in the IFL + placebo group than in IFL + Avastin group (16 vs. 20).
In the study of 1,392 patients who received IFL + Avastin in 53 (14%) and 396 patients receiving IFL + placebo in 30 (8%) thrombotic events occurred receiving full-dose warfarin therapy . Each of two patients in each group (total 4) the resulting bleeding complication. In the two receiving Avastin and full-dose warfarin treatment for patients, such incidents with their blood clotting function of the international normalized ratio. Of the 53 who received IFL + Avastin treated patients 11 (21%) and 30 receiving IFL + placebo in patients treated in one (3%) re-emerged in the thrombotic events.
Other serious side effects 【】
The following serious adverse events was considered to be acceptable cytotoxic chemotherapy for cancer patients is not common, and in the clinical study of Avastin at least one person took place.
Body: serositis
Digestive: intestinal obstruction, intestinal necrosis, mesenteric venous occlusion, anastomotic ulceration.
The blood and lymphatic system: pancytopenia
Metabolic / nutritional disorders: hyponatremia
Urogenital System: Ureteral limited.
【Excessive】
The maximum tolerated dose of Avastin is not clear. The greatest test of human dose (20 mg / kg IV), 16 patients were 9, headache, 3 of whom are severe headaches.
Dosage and usage of recommended dose of 5 mg / kg, the first 14 days of delivery 1, intravenous infusion until disease progression. In the main, within 28 days after the operation should not begin treatment Avastin. Avastin treatment started before the surgical incision should be fully healed.
【Dosage adjustment】
Is not recommended the use of Avastin treatment dose reduction. If necessary, the following methods Avastin should be used to disable or temporarily postponed.
If patients with gastrointestinal perforation; requires that the medical treatment of wounds cracking; severe bleeding; nephrotic syndrome, or hypertensive crisis should be permanently disabled. If patients need further testing before deciding on a moderate to severe proteinuria and medical treatment of severe hypertension have not yet control is recommended to use a temporary postponement. Moderate to severe proteinuria in patients who continued to use or to temporarily postpone the risk of the use of Avastin not yet clear. In the elective surgery before the Avastin should be suspended a few weeks. (See WARNINGS: Gastrointestinal Perforation / Wound Healing Complications and PRECAUTIONS: Surgery). Surgical incision should heal completely before re-start the use of Avastin.
Preparation】 【Use
Professional health workers through the use of Avastin should be diluted before infusion of aseptic technique. By 5 mg / kg of Avastin to extract the required dose, diluted to a total volume of 100 mL of 0.9% sodium chloride injection
, (U.S. patent). As the product contains no preservatives, should be discarded in the remainder of the vial. As injection drug use before, should be inspected visually for particulate matter and discoloration.
Avastin diluted solution should be stored at 2-8 ° environment for up to 8 hours. Avastin with the PVC and polyolefin bags do not incompatible.
Avastin should not use the sugar solution prepared or mixed with sugar solution.
【Use】
Avastin should be the first application of chemotherapy for more than 90 minutes after the intravenous infusion. If the first infusion is well tolerated, the second infusion for 60 minutes or more. If 60 minutes is also well tolerated, subsequent infusions can be controlled in more than 30 minutes.
【Stability and preservation】
Avastin should be kept in refrigerator at 2-8 °, the dark stored in the original carton until use.
Packaging: There are two kinds of 4ml and 16ml size, in order to be placed in the sterile solution of one-off glass, a bottle containing respectively 100 and 400 mg of Bevacizumab. A single 100 mg Package: Includes a bottle of 4ml of Avastin. (25 mg / mL). NDC 50242-060-01 606 single 400 mg Package: Includes a bottle of 16ml of Avastin. (25 mg / mL). NDC 50242-060-02 608.
Shelf life: 3 years
Manufacturer: Roche Group
References: 1. Presta LG, Chen H, O \ 'Connor SJ, Chisholm V, Meng YG, Krummen L, et al. Humanized anti-vascular endothelial growth factor receptor monoclonal antibody for the treatment of solid tumors and other ailments. Cancer Res 1997; 57:4593-9.
Avastin approved as second-line treatment of advanced colorectal cancer drugs (2006-6-22)
Bio-pharmaceutical company Genentech in June 20, said, FDA has approved the expansion of Avastin indications that, as second-line treatment of advanced colon cancer.
Previously, Avastin + chemotherapy combined with advanced colorectal cancer has been approved as first-line treatment drugs.