Avastin is an innovative antitumor drug that has recently appeared in the pharmacy assortment. The drug is in demand in oncology practice due to its ability to fight the most aggressive forms of cancer. Avastin contains recombinant humanized antibodies that are not toxic to the human body. But during treatment there is a possibility of developing adverse reactions. Therefore, it is advisable to use the drug only as prescribed by a doctor in the dosage regimen specified by him.
Characteristics of Avastin
Avastin is a product of genetic engineering. Its composition is formed from nucleic acids, which were obtained by combining foreign fragments with nucleotides. This combination is considered in medicine and pharmacology to have properties as close as possible to the cells of the human body. Monoclonal antibodies selectively combine with the bioactive factor VEGF, which leads to its rapid neutralization. The malignant tumor gradually decreases in size and then disappears altogether.
Avastin is available in the form of a fine crystalline powder. This is a concentrate that is diluted with an isotonic sodium chloride solution before use. The powder is packaged in glass bottles with rubber stoppers and aluminum caps of 4 or 16 ml. The cardboard box also contains an annotation, the recommendations of which will help to carry out the treatment correctly.
What is Avastin for?
The main indication for treatment with Avastin is malignant neoplasms, including those complicated by metastases. Oncologists prescribe the drug to patients after diagnosing the following pathologies:
- colorectal cancer - a tumor that forms in the rectum, as part of complex therapy;
- inoperable forms of lung cancer in combination with drugs containing platinum compounds;
- malignant neoplasms affecting renal structures, together with immunomodulators alpha-2a interferons;
- focal cancer localized in the fallopian tube, ovary, one of the abdominal organs in combination with Carboplatin or Paclitaxel.
Avastin is also included in therapeutic regimens when other anticancer drugs are ineffective.
The importance of suppressing neoangiogenesis for the treatment of malignant tumors is increasingly being confirmed in clinical studies, in particular with the use of Avastin (bevacizumab), a monoclonal antibody that suppresses VEGF, a vascular endothelial growth factor primarily responsible for the formation of tumor vessels. The effectiveness of bevacizumab (in monotherapy and in combination with chemotherapy) has been shown in several studies for colorectal cancer, non-small cell lung cancer, and kidney cancer.
In 2005, a series of papers was published presenting the results of recent studies on the effectiveness of Avastin in various solid tumors.
Avastin for colorectal cancer
Hochster HS et al. [1] conducted a study (TREE 1 and 2) that included 360 patients with advanced colorectal cancer. All patients in the 1st line received various regimens with oxaliplatin and fluoropyrimidines (jet or long-term administration of fluorouracil, capecitabine), including Avastin or without it. The following regimens were evaluated: FOLFOX (oxaliplatin 85 mg/m2, calcium folinate 350 mg/m2, fluorouracil 2400 mg/m2, 46-hour infusion every 2 weeks); bFOL (oxaliplatin 85 mg/m2 on days 1 and 15, calcium folinate 20 mg/m2 IV bolus + 5-fluorouracil 500 mg/m2 IV bolus on days 1, 8 and 15, every 4 weeks ); CapOx (oxaliplatin 130 mg/m2 on day 1, capecitabine 850 mg/m2/day on days 1–14, every 3 weeks). The second group of patients received the same chemotherapy regimens plus Avastin at a dose of 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks. The effectiveness of the modes is presented in table. 1.
It was shown that the addition of Avastin to chemotherapy significantly increased the immediate effectiveness of treatment without increasing toxicity. Time to progression and overall survival are being studied.
In the 1st line of treatment for colorectal cancer, Fernando N. and Yu D. [2] studied the combination of XELOX + Avastin (oxaliplatin 85 mg/m2 on day 1, capecitabine 1000 mg/m2 on days 1–5 and 8–12 followed by dose reduction to 850 mg/m2, Avastin 10 mg/kg on day 1, every 2 weeks). In 30 patients, the overall effectiveness was 56.7%, stabilization (≥ 4 months) – 36.7%. The median time to progression was 11.9 months. 30% of patients had grade III diarrhea (mainly in patients receiving capecitabine 1000 mg/m2/day). Reducing the dose of capecitabine to 850 mg/m2/day allowed for safe treatment.
In phase II studies, Saltz LB and Lenz H. [3] assessed the effectiveness and safety of simultaneous administration of two monoclonal antibodies - Avastin and cetuximab (monoclonal antibody against epidermal growth factor) in patients with metastatic colorectal cancer with progression after 1st line IFL (irinotecan , fluorouracil, calcium folinate). Forty patients continued IFL chemotherapy as usual, also receiving Avastin 5 mg/kg every 2 weeks and cetuximab loading dose 400 mg/m2, then 250 mg/m2 weekly; 35 patients received only Avastin and cetuximab in the same regimen without chemotherapy. The results of the study are presented in table. 2.
The study showed that the combination of Avastin and cetuximab was sufficiently effective without the use of chemotherapy, but the addition of irinotecan improved treatment results.
In the phase III study by Giantonio B. and Catalano P. [4], 822 patients previously treated with fluoropyrimidines and/or irinotecan were randomized into three groups: Avastin 10 mg/kg IV every 2 weeks alone, or FOLFOX chemotherapy 4 (every 2 weeks: oxaliplatin 85 mg/m2 on day 1, calcium folinate 200 mg/m2 intravenously for 2 hours, fluorouracil 400 mg/m2 intravenously in a bolus followed by a 22-hour infusion on days 1 and 2 days), or FOLFOX–4 + Avastin. The results of the study are presented in table. 3.
The addition of Avastin to chemotherapy has been shown to significantly improve overall treatment efficacy, as well as time to progression and overall survival compared with chemotherapy alone or Avastin alone. Avastin did not increase chemotherapy toxicity.
Avastin for breast cancer
In breast cancer, neoangiogenesis has been shown to be of great importance for invasion and metastasis. Clinical data also confirm that in patients without regional lymph node involvement, high vascular density and overexpression of VEGF correlate with a high risk of developing metastases and low rates of disease-free and overall survival. In addition, increased VEGF expression is associated with decreased effectiveness of endocrine therapy and chemotherapy.
Preclinical and clinical data have been obtained on the use of Avastin in combination with the HER-2 inhibitor trastuzumab (Herceptin). It turns out that HER-2 is involved in the regulation of VEGF. In vitro studies have demonstrated increased expression of HIF-1alpha and VEGF in a population of cells overexpressing HER-2, with trastuzumab significantly reducing VEGF expression.
In animal models of breast cancer, estrogens have been shown to induce VEGF expression, whereas aromatase inhibitors have the opposite effect [5]. It has been hypothesized that estrogen-induced VEGF expression promotes the growth of breast cancer, and therefore anti-estrogen therapy (aromatase inhibitors) in combination with Avastin may be effective in this disease.
In an ongoing open-label phase III study, Miller et al. [6] are studying Avastin in combination with paclitaxel as 1st line therapy for metastatic breast cancer. Previously, patients could receive adjuvant chemotherapy with taxanes ± Herceptin if the disease-free period exceeded 12 months. The 715 patients included in the study were randomized into 2 groups: paclitaxel 90 mg/m2 weekly for 3 weeks followed by a week break (n = 350) or paclitaxel 90 mg/m2 weekly for 3 weeks + Avastin 10 mg/kg every 2 weeks (n = 365). The results are presented in table. 4.
The addition of Avastin in first-line treatment for metastatic breast cancer has been shown to significantly improve overall treatment efficacy and increase time to progression and overall survival.
Taking these data into account, Avastin is currently being studied in combination with chemotherapy (docetaxel, capecitabine), endocrine therapy (letrozole), and targeted therapy drugs (trastuzumab, EGFR inhibitors).
Avastin for kidney cancer
Most patients with clear cell renal cell carcinoma have loss of the Von Hippel Lindau protein, caused by a gene mutation and causing overexpression of VEGF.
A phase II multicenter trial [7] evaluated a combination of Avastin, a potential VEGF inhibitor, and erlotinib (Tarceva, a small molecule inhibitor of epidermal growth factor receptors) in patients with metastatic clear cell renal cell carcinoma. All patients received Avastin 10 mg/kg IV every 2 weeks + erlotinib 150 mg daily. 43 (68%) patients had not previously received treatment, and 20 (32%) patients were treated with interleukin-2 and/or interferon.
In 15 (25%) of 59 patients, an objective effect was observed, in an additional 22% there was minimal regression (10–30%). Stabilization of the disease was noted in 23 (39%) patients. The median time to progression was 11 months; 80% of patients with partial remission did not progress within one year, 57% with a minor effect, 27% with stabilization.
The results demonstrate the effectiveness of the Avastin + erlotinib combination in metastatic kidney cancer.
Avastin for non-small cell and small cell lung cancer
The role of angiogenesis has also been shown in lung cancer, and high vascular density and high VEGF levels are considered as a prognostic factor for metastasis and poor prognosis in this disease. Inhibition of angiogenesis may be a therapeutic strategy in the treatment of lung cancer.
In a randomized phase III trial of 855 patients with stage IIIb/IV non-small cell lung cancer who received paclitaxel 200 mg/m2 and carboplatin AUC 6 (CP regimen) every 3 weeks with or without Avastin 15 mg/kg every 3 weeks, the following results (Table 5) [8].
The addition of Avastin to paclitaxel and carboplatin has been shown to significantly improve treatment efficacy, time to progression and overall survival.
To evaluate the effectiveness and safety of the simultaneous use of Avastin and the EGFR inhibitor erlotinib (Tartseva), a phase I–II clinical trial was conducted [9], which included 34 patients with locally advanced or metastatic non-small cell lung cancer who received erlotinib 150 mg/day orally daily for 21 days and Avastin 15 mg/kg IV every 21st day. The results of the study are presented in table. 6. This combination has been shown to be effective in non-small cell lung cancer.
A phase II study [10] assessed the safety and efficacy of irinotecan + carboplatin + radiotherapy followed by the addition of Avastin in patients with locally advanced small cell lung cancer. In the study, 41 patients received carboplatin (AUC 5) IV on day 1 and irinotecan 50 mg/m2 IV on days 1 and 8, every 3 weeks, with concurrent radiotherapy (DOD 1.8 Gy, SOD 61.2 Gy) starting from cycle 3; Cycles 3 and 4 were performed every 28 days. Patients who did not experience progression after 4 cycles received Avastin at a dose of 10 mg/kg IV every 2 weeks in the next stage. 37 patients were assessed. Complete effect was achieved in 32% of patients, partial effect – in 49%, disease stabilization – in 19%. The overall effectiveness was 81%, overall survival was 87%. The study results confirm that irinotecan + carboplatin + radiotherapy + Avastin is a safe, well-tolerated and effective treatment for locally advanced small cell lung cancer, and the inclusion of Avastin may improve one- and two-year survival rates.
Avastin for soft tissue sarcoma
In a phase II study, D'Adamo DR et al. [11] evaluated the antitumor activity of the Avastin + doxorubicin combination in 17 patients with metastatic soft tissue sarcoma (11 leiomyosarcoma). Avastin was administered at a dose of 15 mg/kg, doxorubicin – 75 mg/m2 every 3 weeks. In 2 patients with uterine leiomyosarcoma, a partial effect was observed, in 11 patients the disease was stabilized. Two patients were observed without progression for 10+ months. Overall effectiveness was 12%, median time to progression was 8 months, and median overall survival was 16 months. The time to progression rates with Avastin provide the basis for further research.
Avastin for pancreatic adenocarcinoma
A phase II study [12] studied the combination of Avastin 10 mg/kg every 2 weeks + gemcitabine 1000 mg/m2 on days 1, 8 and 15, every 4 weeks in patients with advanced pancreatic cancer who had not received treatment for metastatic diseases. The results are presented in table. 7.
Bevacizumab for hepatocellular cancer
The study by Schwartz J. and Schwartz M. [13] examined the safety and preliminary efficacy of Avastin at doses of 5 mg/kg and 10 mg/kg every 2 weeks for inoperable hepatocellular liver cancer. In 10 of 11 patients receiving Avastin at a dose of 5 mg/kg, and in 3 patients receiving it at a dose of 10 mg/kg, treatment was accompanied by minimal toxicity. A partial effect was obtained in 2 patients. The duration of partial remission in one patient was 11.3 months. In 9 patients with stable disease, progression was noted after 5.5–7.6 months.
Avastin is currently approved in the USA and Europe for use in combination with chemotherapy in the 1st line of treatment for metastatic colorectal cancer. Given the good results of Avastin in breast cancer, non-small cell lung cancer, and kidney cancer, there is no doubt that the indications for the use of this drug will soon be expanded.
How Avastin works
Its course use prevents the formation of additional blood vessels that feed the tumor. It stops increasing in size, growing, and metastasizing. The therapeutic effects of Avastin are due to the properties of its active ingredient bevacizumab, which represents a clinical and pharmacological group of drugs with recombinant monoclonal antibodies. Under its influence, the receptors of growth factors of the first and second types, which are located on the surface of the endothelium, are blocked. First, vascularization decreases, and after some time a decrease in the tumor is noted. How much does the anticancer drug Avastin cost? Go to the corresponding section of the site to find out.
Pharmacokinetics
The maximum therapeutic concentration of the active substance Avastin is ensured by its parenteral administration once every 1-2 times a month. The age of the patient does not affect the clearance of bevacizumab. It is almost a third higher in patients whose blood contains low levels of albumin. The active ingredient is metabolized by proteolytic catabolism by all cells of the body.
Avastin solution concentrate for infusion 100 mg/4 ml 4 ml
Avastin is administered only intravenously; It is impossible to administer the drug intravenously as a bolus or bolus! Avastin is not intended for intravitreal administration. Avastin is pharmaceutically incompatible with dextrose solutions. The required amount of Avastin is diluted to the required volume with 0.9% sodium chloride solution in compliance with aseptic rules. The concentration of bevacizumab in the prepared solution should be in the range of 1.4-16.5 mg/ml. The initial dose of the drug is administered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion can be given over 60 minutes. If the 60-minute infusion is well tolerated, all subsequent infusions can be given within 30 minutes. It is not recommended to reduce the dose of bevacizumab due to adverse events. If necessary, treatment with Avastin should be stopped completely or temporarily. Standard dosage regimen. Metastatic colorectal cancer. As first line of therapy: 5 mg/kg once every 2 weeks or 7.5 mg/kg once every 3 weeks as an intravenous infusion, long-term. It is recommended that Avastin therapy be continued until signs of disease progression or unacceptable toxicity occur. As a second-line therapy: patients previously treated with Avastin after the first progression of the disease can continue treatment with Avastin, subject to a change in chemotherapy regimen: - if the disease progresses after first-line therapy that included Avastin: 5 mg/kg once every 2 weeks or 7.5 mg/kg once every 3 weeks as an intravenous infusion, long-term; — with disease progression after first-line therapy that did not include Avastin: 10 mg/kg once every 2 weeks or 15 mg/kg once every 3 weeks as an intravenous infusion, long-term. Locally recurrent or metastatic breast cancer (BC) 10 mg/kg once every 2 weeks as an intravenous infusion, long-term. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. Advanced inoperable, metastatic or recurrent non-squamous non-small cell lung cancer. — First-line therapy for non-small cell lung cancer in combination with platinum-based chemotherapy. Avastin is prescribed in addition to platinum-based chemotherapy (maximum duration of chemotherapy is 6 cycles), then Avastin is continued as monotherapy. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. Recommended doses: - 7.5 mg/kg once every 3 weeks as an intravenous infusion in addition to cisplatin-based chemotherapy; — 15 mg/kg once every 3 weeks as an intravenous infusion in addition to carboplatin-based chemotherapy. — First-line therapy for non-small cell lung cancer with activating mutations in the EGFR gene in combination with erlotinib 15 mg/kg once every 3 weeks as an intravenous infusion in addition to erlotinib therapy. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. For patient selection and dosing information, see the complete prescribing information for erlotinib. Advanced and/or metastatic renal cell carcinoma. 10 mg/kg once every 2 weeks as an intravenous infusion, long-term. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. Glioblastoma (glioma grade IV according to WHO classification). For newly diagnosed disease: 10 mg/kg once every 2 weeks as an intravenous infusion in combination with radiation therapy and temozolomide for 6 weeks. After a 4-week break, Avastin administration is resumed at a dose of 10 mg/kg once every 2 weeks in combination with temozolomide. Temozolomide is prescribed in 4-week cycles, the duration of temozolomide therapy is up to 6 cycles. Further, the administration of Avastin continues as monotherapy at a dose of 15 mg/kg once every 3 weeks. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. For recurrent disease: 10 mg/kg once every 2 weeks as an intravenous infusion, long-term. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. Epithelial cancer of the ovary, fallopian tube and primary peritoneal cancer As first line of therapy: 15 mg/kg once every 3 weeks as an intravenous infusion in addition to carboplatin and paclitaxel (maximum duration of chemotherapy 6 cycles), then Avastin continues as monotherapy . The total duration of therapy with Avastin is 15 months. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. For recurrent disease: - sensitive to platinum drugs: 15 mg/kg once every 3 weeks as an intravenous infusion in combination with carboplatin and paclitaxel (6-8 cycles); then the administration of Avastin continues as monotherapy or 15 mg/kg once every 3 weeks as an intravenous infusion in combination with carboplatin and gemcitabine (6-10 cycles), then the administration of Avastin continues as monotherapy. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. - resistant to platinum drugs: 10 mg/kg once every 2 weeks as an intravenous infusion in combination with one of the following drugs: paclitaxel, topotecan (with a “weekly” regimen of topotecan administration - that is, on days 1, 8 and 15 every 4 weeks) or pegylated liposomal doxorubicin or 15 mg/kg once every 3 weeks as an intravenous infusion in combination with topotecan administered daily for 5 consecutive days every 3 weeks. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. Persistent, recurrent or metastatic cervical cancer 15 mg/kg once every 3 weeks as an intravenous infusion in combination with chemotherapy regimens: paclitaxel and cisplatin or paclitaxel and topotecan. If signs of disease progression or unacceptable toxicity occur, Avastin therapy should be discontinued. Dosage regimen for special groups of patients. Children and teenagers. Avastin is contraindicated in children under 18 years of age. The safety and effectiveness of Avastin in patients under 18 years of age has not been established. The addition of Avastin to standard therapy in clinical trials did not show clinical benefit in pediatric patients with high-grade glioma and in pediatric patients with metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma. The publications describe cases of osteonecrosis of various localizations, except for osteonecrosis of the jaw, observed in patients under the age of 18 years who received Avastin®. Elderly patients (over 65 years of age) No dose adjustment is required in patients over 65 years of age. Patients with renal impairment The safety and effectiveness of bevacizumab in patients with renal impairment have not been studied. Patients with liver failure. The safety and effectiveness of bevacizumab in patients with hepatic impairment have not been studied. Instructions for use, handling and destruction. Before use, the solution must be inspected for mechanical inclusions and color changes. Avastin does not contain an antimicrobial preservative, so it is necessary to ensure that the prepared solution is sterile and use it immediately. If the drug is not used immediately, then the time and storage conditions of the prepared solution are the responsibility of the user. The prepared solution can be stored for no more than 24 hours at a temperature from +2°C to +8°C, if the dilution is carried out under controlled and validated aseptic conditions. The chemical and physical stability of the prepared solution is maintained for 48 hours at temperatures from +2°C to +30°C in a 0.9% sodium chloride solution. The unused drug remaining in the bottle is destroyed, as it does not contain preservatives.
Instructions for use
You can find out the cost of the antitumor drug from our catalog. Avastin is used as an injection solution for intravenous administration. During the preparation of the medicine, compliance with the rules of asepsis is required. When calculating single doses, the oncologist takes into account the type of cancer, tumor size, and severity of symptoms. He focuses on the patient’s age and the presence of other chronic diseases. When the concentrate is mixed with an isotonic solution, a drug is obtained in which the content of bevacizumab varies between 1.4–16.5 mg/ml. There are several nuances to Avastin therapy:
- The first treatment procedure cannot last less than one and a half hours. If no adverse reactions occur, then the next intravenous administration lasts no more than an hour.
- The injection solution is administered not by junior medical personnel, but by an oncologist with practical experience in treating cancer with monoclonal antibodies.
- Throughout the treatment, the patient's condition is monitored based on functional indicators of the liver and kidneys.
No dosage adjustment is required for elderly and senile patients. But it is necessary for people with liver and kidney pathologies.
Avastin in ophthalmology
Avastin is a medical drug used in the treatment of ophthalmic diseases since 2004. It was developed as an oncological agent that can slow down the growth of tumors and reduce their volume for subsequent surgical treatment. However, in the course of clinical studies, another ability was noted - to slow down the growth of newly formed vessels, which is now successfully used in ophthalmology in the treatment of age-related macular degeneration and other eye diseases accompanied by abnormal proliferation of blood vessels (neovascularization).
Thus, injections of Avastin into the vitreous body for proliferative diabetic retinopathy turned out to be very effective and well tolerated by patients. In addition, it is highly effective in stabilizing the development of the subretinal neovascular membrane - the growth of newly formed vessels in the fundus.
Ophthalmological practice of using Avastin shows that in the majority of patients, after treatment there was a significant improvement in the functional state of the organ of vision. The drug is especially effective in cases of hemorrhages into the vitreous body, with neovascularization of the iris. Intravitreal administration of the drug is also used in the treatment of wet forms of macular degeneration in the elderly, macular edema, diabetic retinopathy, and neoplasms of the perimacular region.
The effect of Avastin administration is expressed in the thinning of the macular region of the retina and stabilization of the subretinal neovascular membrane, which is confirmed by fluorescein angiography, which shows a decrease in fluorescein extravasation.
Injections of the drug into the vitreous minimize the risk of developing systemic side effects due to microdosing, which is sufficient for a targeted effect (400-500 times less than the dose used for intravenous administration), however, even this allows the doctor to create the necessary concentration of the substance in a given area. Avastin in a dosage of 1.25 mg is injected into the vitreous body once every 3-4 weeks. The maximum effect is often observed immediately after the first injections.
Since the beginning of the use of Avastin, there have been positive changes in the treatment of the wet form of age-related macular degeneration. This drug has high effectiveness and affordable cost. The response to treatment with it, as studies show, does not depend on photodynamic therapy and the administration of the drug Macudzhen - the results will be the same as with treatment carried out for the first time. In addition, there are no age restrictions when treating AMD with Avastin.
The limitations of using the drug intraocularly include only childhood, pregnancy, and the period of breastfeeding, due to the rather painful procedure for intraocular administration.
Over the past years since the drug was first used in ophthalmology, a large number of scientific papers have been published regarding Avastin therapy methods, with an analysis of the results obtained in the treatment of patients with the exudative form of AMD. The conclusion of these studies is clear: thanks to the administration of Avastin, there is a significant increase in visual acuity in almost a third of patients, and in more than half of patients, visual acuity is stabilized.
Contraindications to treatment with Avastin
An absolute contraindication to antitumor therapy is hypersensitivity to one of the components. Avastin is used with caution in the treatment of patients with the following pathological conditions:
- hypertension;
- thromboembolism;
- hemorrhagic diathesis;
- blood clotting disorders;
- severe cardiovascular diseases;
- agranulocytosis;
- history of perforation of ulcers;
- acquired coagulopathy;
- proteinuria.
In pediatric practice, treatment with Avastin is prohibited. This is also true during pregnancy and breastfeeding. For patients with severe renal or liver failure, safer drugs are selected.
Cancer immunotherapy in Israel
Russian Medical Server / Cancer immunotherapy in Israel / Avastin (Bevacizumab) - cancer treatment in Israel
Innovative drug Avastin for immunotherapy in Israel
Avastin is a medicine that prevents the vascular system from supplying cancer tumors with nutrients and oxygen. Thanks to this process, it becomes possible to change the formation from malignant to chronic. In turn, this makes it possible to perform operations on tumors that previously could not be removed.
General information about the medicine
Avastin (Bevacizumab) is an antibody produced by immune cells. As mentioned above, the substance interferes with VEGF (vascular endothelial growth factor). This factor is the main one in triggering the growth of the number of vessels that feed the tumor.
In addition to stopping the expansion of the circulatory system, Avastin is also used to control tumors and their metastasis (recurrence of cancer).
Story
The development of drugs that prevent antiogenesis (supply of tumors through blood vessels) began quite recently, at the end of the 20th century. The first successful experience of therapy with such drugs was recorded in 1989. Then, since 1992, active research and development of similar drugs for the treatment of malignant tumors began. In 1997, the results of some experiments were published in the journal Nature; they showed a decrease in cancer formations after treatment with antiogenic drugs. A year after that, scientists created the first laser to prevent the formation of blood vessels for tumors, and a year later the first course of antiangiogenic therapy was developed. It was approved by the FDA, and after that even more active research and development began in this area. In 2003, Avastin (Bevacizumab), the first antiangiogenic drug, was created and showed good patient survival.
A number of studies have confirmed that the drug increases survival for any type of tumor. The drug is approved in Russia and Europe for the treatment of four main types of cancer in the final stages - cancer of the rectum and colon, breast, lungs and kidneys. According to statistics, about three million people die from these diseases every year.
In the USA, the medicine is approved by the FDA (Food and Drug Administration). In North America, the drug is used to treat five types of cancer - breast, colorectal, kidney and lung.
Currently, about 500 thousand people have received treatment with Avastin. The international company Roche, which is the largest drug manufacturer in the world, annually sponsors research on the drug. In total, more than 455 studies of the drug were conducted on seven types of malignant tumors at different stages of development.
Indications and contraindications for use
Unfortunately, Avastin cannot be used in all cases. The drug is prescribed for intestinal cancer, when the tumor has begun to spread to other organs (metastatic type of disease, characteristic of the last stage of the disease). In this case, the medicine is prescribed in combination with chemotherapy.
This remedy is also prescribed in the case of a malignant tumor of the mammary glands, when the cancer has developed into a locally recurrent form (re-formation of a tumor in the same place). In this case, treatment is carried out in combination with taxane-based chemotherapy. This method of treatment is used as first-line therapy.
Another indication for Avastin is relapse of lung cancer. The medicine is used if surgery cannot be performed. This therapy is also used primarily from the moment of diagnosis. The complex also includes chemotherapy based on platinum substances.
Another medicine is prescribed for renal cell carcinoma. With this disease, damage to the epithelium of the kidney occurs. In this case, Avastin is taken in combination with interferon Alpha 2a.
The drug is also prescribed for brain tumors (glioblastoma). This type of education is considered the most dangerous. These patients should take Avastin as their primary medication or in combination with irinotecan if the person relapses.
The medicine also has some contraindications.
The drug should not be taken:
· during pregnancy;
· during breastfeeding;
· if you are allergic to any components of the drug;
· if you are allergic to medications made using Chinese hamster ovary cells and other similar components;
· if the patient is a child (safety and effect are unknown);
· in case of kidney or liver failure (safety and effect unknown).
Avastin should also be taken with caution in case of arterial hypertension accompanying cancer, or clogging of blood vessels with blood clots. There are some restrictions for people over 65 years of age, so the use of the medicine in very elderly patients should be carefully monitored. It is not yet advisable to take Avastin during the healing of a serious wound or stopping bleeding. In addition, it is not recommended for patients with stomach or intestinal ulcers, as well as people with serious diseases of the heart and vascular system.
Side effects and overdose
Patients may experience some side effects from this drug. For example, a gastrointestinal ulcer, bleeding into the lungs, coughing up blood (most often occurs in people with a tumor in the lungs), the appearance of blood clots in the vessels. In addition, increased blood pressure, weakness, abdominal pain and diarrhea are possible.
The vascular system can also react to taking the medication. Many patients experience a decrease in white blood cells, neutrophils in the blood, and anemia.
As mentioned above, an ulcer may appear while taking the drug. In addition, from the gastrointestinal tract, nausea, stool disorders, anorexia, intestinal obstruction, etc. are possible.
It is also possible to change the shade of the skin - redness, dermatitis, etc.
As for the nervous system, a change in taste perception, migraine, increased drowsiness, etc. may occur.
In addition, increased lacrimation and visual impairment are noted as a side effect of the medication.
The maximum dose of Avastin is 20 mg/kg. If an overdose occurs, all of the above effects may be enhanced.
Features of application
Firstly, the drug is taken strictly under the supervision of a doctor. In addition, it should be remembered that Avastin slows down wound healing. So if an operation has been performed, then you need to start the course of treatment no earlier than a month after the surgery. If any complication occurs, it is better to stop taking Avastin.
The drug can be taken only after measuring blood pressure. If a person has hypertension, then while the condition stabilizes, you need to stop taking the medication for a while. If there is a risk of crisis, it is not recommended to take the medicine. If the patient has a history of hypertension, then the amount of protein in the urine may increase.
If a person has poor blood clotting or chronic hemorrhagic diathesis, the drug should also be taken with caution. You also need to carefully monitor doses if the patient has lung cancer or there is a risk of excessive hemoptysis. They can be caused by treatment with anti-inflammatory drugs, radiation therapy, the development of a tumor in the center of the lung, or the deposition of fatty plaques in the blood vessels. If a person regularly coughs up 2.5 ml. blood and higher, then Bevacizumab should be stopped.
If the cancer is in the intestines, there may be bleeding from the rectum while taking the medicine. In addition, during the studies, blood discharge from the nose was observed. Typically the nosebleed lasted about 5 minutes or less. This occurred in 40% of people. Increased gum bleeding is also possible.
Despite the fact that the drug had high survival rates, Avastin provokes blockage of blood vessels with blood clots (thromboembolism), a heart attack. Moreover, the risk of both occurrences is much higher than when prescribing chemotherapy alone. If the patient is over 65 years of age, thromboembolism occurs even more often, so doses must be prescribed very carefully.
Sometimes a person may develop late-onset encephalopathy (destruction of the white matter of the brain that affects mental abilities). In this case, you should stop taking Avastin completely and monitor your blood pressure. Unfortunately, doctors cannot say for sure what might happen if Bevacizumab treatment is reintroduced later.
If a patient is diagnosed with breast cancer, there is a high risk of congestive heart failure. So in the case of a history of cardiovascular disease, you need to think very seriously about the doses and consequences.
Quite often, after a course of Avastin, a person with an intestinal tumor developed fistulas (inflammation) in the stomach or intestines. In rare cases, a fistula may appear in other parts of the body. Most often, inflammation appears after six months of taking Bevacizumab, but sometimes doctors diagnose it after a year or even one week of therapy. If a fistula appears in the gastrointestinal tract, the person should stop taking the medicine. In case of inflammation in other parts of the body, cessation of therapy is decided individually.
If Avastin is taken in combination with other chemotherapy drugs that interfere with the process of hematopoiesis, neutropenia (a decrease in the number of neutrophils in the blood) or infection may develop. Sometimes a patient can be diagnosed with both at the same time, in such cases the risk of death is high.
When taking Avastin by people over 65 years of age, there is a high risk of arterial blockage with blood clots leading to the development of stroke, heart attack and micro-stroke. Diarrhea, headache, weakness, etc. are also possible.
General data based on Avastin studies
In the ECCO and ESMO studies, it was proven that the drug in combination with chemotherapy (based on Xeloda) reduces and completely eliminates liver metastases in 80% of patients suffering from metastatic (the tumor has spread to neighboring organs) colon cancer. Therefore, a third of patients with malignant tumors can undergo surgery to remove metastases. As a result, about 60% of people were successfully operated on.
The BOXER study was also conducted, which studied the body's response in patients with stage 2 liver metastases to Avastin in combination with XELOX (a drug based on Xeloda, taken orally, Oxaliplatin is administered intravenously in the complex). The result was also positive - patients who took Xeloda had a higher survival rate than those who underwent standard chemotherapy. After this, XELOX complex was also given to patients with stage three colon cancer. As a result, 71% of people achieved three-year survival; the group of patients taking a different course of chemotherapy showed the same survival rate in only 66.5% of cases.
The First BEAT study showed that the drug is equally effective in young and elderly patients. This is a very important discovery, because... The elderly population rarely appears in such experiments.
According to statistics, colon and rectal cancer is the third most common disease (about 600 thousand people die from this disease every year). In addition, this is the second most dangerous cancer disease (after brain cancer), so reducing the risk of relapse with the help of Avastin in combination with Xeloda will please many.
There is also a study NO16968, during which scientists observed the effects of the XELOX therapeutic complex for six months. About 2,000 people suffering from colon cancer took part in the experiment. NO16968 was conducted in 29 countries and 226 research centers. The main result of the study showed that people's survival rate increased without the risk of tumor recurrence.
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