Cizumab is an anti-neoplastic medication which is containing Bevacizumab as an active substance, which is involved in the treatment of various cancers. It is a monoclonal antibody, which target a tumor cell protein known as vascular endothelial growth factor (VEGF). This VEGF is responsible for cancer to form their blood vessels, so they can easily acquire food and oxygen from blood for survival. The treatment involved by interceding with development of blood supply, so it is termed as anti-angiogenesis therapy.
Indication of Cizumab
The most important prescribing information of Cizumab is;
Metastatic colorectal cancer:
In this condition, Cizumab should be used in combination with intravenous 5-FU based chemotherapy. This is considered as first or second line therapy. Cizumab is concurrently used with fluoropyrimidine Irinotecan or fluoropyrimidine oxaliplatin based therapy should be used as second line treatment in advanced colon rectal cancer for the patients who are advanced with first line therapy of Cizumab. Cizumab is not a supporting therapy for colon cancer.
Non-squamous non-small cell lung cancer:
Cizumab is used as first line therapy for this condition by combining with carboplatin & paclitaxel.
Cizumab is majorly used in this condition
Advanced renal cell cancer:
In this condition, Cizumab should be combined with interferon alfa medicine.
Advanced cervical cancer:
For treating this condition, Cizumab should be concurrently used with paclitaxel & cisplatin or paclitaxel & topotecan.
Epithelial ovarian, fallopian tube or primary peritoneal cancer:
Cizumab should be combined with carboplatin & paclitaxel, followed by Cizumab as a single therapy. In platinum resistance epithelial ovarian, fallopian or peritoneal cancer, Cizumab should be combined with paclitaxel, pegylated liposomal doxorubicin or topotecan. In platinum sensitive recurrent epithelial ovarian, fallopian tube or peritoneal cancer, Cizumab should be combined with carboplatin & paclitaxel or carboplatin & gemcitabine.
Mechanism of action of Cizumab
Bevacizumab is majorly binds to the protein like vascular endothelial growth factor and prevent the interaction of protein to its receptors. The communication of protein with its receptors causes cell production by forming new blood vessels which comes under the process of angiogenesis. Bevacizumab is involved in inhibition of new blood vessel formation leads to death of cancer cells due to loss of oxygen and food.
The pharmacokinetic of Cizumab is to be linear; the concluded time to reach more than 90% of steady state concentration is 84 days. The median trough concentration of Bevacizumab is 80.3mcg/ml on day 84.
Volume of distribution of Bevacizumab is 2.9L
The drug has been experienced with opsonization for elimination. This may occur through reticuloendothelial system at time of binding to endothelial cells.
The terminal half-life period of Bevacizumab is nearly 20 days. Creatinine clearance value is 0.23 (33)L/day
Dosage regimens and administration of Cizumab
The most important administration factors are, Cizumab should not be used until at least 28 days following surgery and lesion is completely healed.
Advanced colon rectal cancer
Cizumab combined with 5-FU The dose of Cizumab is; The dose of 5mg/kg of Cizumab should be taken for every 2 weeks administered through intravenously in combination with bolus IFL. 10mg/kg of Cizumab should be taken for every 2 weeks administered intravenously by combining with FOLFOX4. The dose of Cizumab is 5mg/kg should be administered intravenously as every 2 weeks or 7.5mg/kg should be given IV for every 3 weeks by combining with fluoropyrimidine Irinotecan or fluoropyrimidine oxaliplatin based chemotherapy regimens.
Non-squamous non-small cell lung cancer
The suggested dose of Cizumab is 15mg/kg should be administered through IV for every 2 weeks by combining with carboplatin & paclitaxel.
The usual suggested dose of Cizumab is 10mg/kg should be administered IV for every 2 weeks
Advanced renal cell cancer
The usual suggested dose of Cizumab is 10mg/kg should be given intravenously for every 2 weeks by combining with interferon alfa.
Advanced cervical cancer
The advised dose of Cizumab in this condition is 15mg/kg of drug should be given intravenously for every 3 weeks by combining with paclitaxel & cisplatin or by combining with paclitaxel & topotecan.
Epithelial ovarian, fallopian tube, or peritoneal cancer
Therapy of stage III or IV: The usual dose of Cizumab is 15mg/kg IV for every 3 weeks by combining with carboplatin & paclitaxel for period of 6 cycles, continued by Cizumab 15mg/kg for every 3 weeks as a single regimen, for total duration of treatment is 22 cycles.
Therapy of frequent disease
Platinum resistance condition
The prescribed dose of Cizumab is 15mg/kg given IV for every 3 weeks by combining with topotecan (every 3 weeks).
The prescribed dose of Cizumab is 15mg/kg should be given as IV for every 3 weeks, by combining with carboplatin & paclitaxel for period of 6 to 8 cycles, continued by Cizumab 15mg/kg for every 3 weeks as a single regimen. The prescribed dose of Cizumab is 15mg/kg IV for every 3 weeks by combining with carboplatin & gemcitabine for period of 6 to 10 cycles, continue with Cizumab 15mg/kg as a single regimen.
Cizumab should be administered through intravenous infusion over the period of 90 minutes as first infusion and consecutive infusions may follow over 60 minutes. 100mg of Cizumab containing 4ml solution which is diluted in 100ml of 0.9% sodium chloride solution. Cizumab should not be diluted in dextrose solution. Cizumab should be administered as intravenous site. It should be administered with or without food.
There is no chance of getting over dosage in Cizumab receiving patients, because Cizumab is a cytotoxic drug which is administered only under the supervision of medical oncologist. Cizumab should be used cautiously.
Common side effects
Diarrhea, Nausea, Stomatitis, Fatigue, Arthralgia, Muscle weakness, Pain, Dysarthria, Headache, Dyspnea, Epistaxis, Nasal mucosal disorders, Hypertension, Neutropenia, Mucosal inflammation, Peripheral sensory neuropathy, Palmar plantar erythrodysaesthesia, Contusion, Back pain, Insomnia
The most common adverse effects in Cizumab treatment
GI perforations & fistulae, Surgery and wound healing complications, Hemorrhage, Arterial thromboembolic events, Venous thromboembolic events, Hypertension, Posterior reversible encephalopathy syndrome, Renal damage & Proteinuria, Infusion reactions, Ovarian failure, Congestive heart failure
Some warning signs should be taken into consideration:
Gastrointestinal perforation, surgery & wound lesions complexity or hemorrhages are the major adverse effect occurs during the treatment with Cizumab injection.
In GI perforation:
Treatment should be discontinued and providing supportive measures
In wound or surgery complications:
Cizumab treatment should be interrupt during the surgery until the wound should be completely healed. Nearly 28 days after & before the surgery, therapy should be withheld.
Severe hemorrhages like GI bleeding, hemoptysis, Hematemesis, CNS hemorrhage, Epistaxis & vaginal bleeding are occurring during the Cizumab treatment. Discontinue the treatment.
Arterial thromboembolic events:
Discontinue the therapy with Cizumab in patients who are suffered with severe ATE.
Venous thromboembolic events:
Incidence of toxicity should be detected; in case of severe condition therapy should be stopped.
Increased blood pressure in patients who are receiving Cizumab therapy, should be monitor frequently with blood pressure and provided with alternative medication for correct the pressure. In hypertension crisis or encephalopathy should be discontinue the treatment.
Posterior reversible encephalopathy syndrome:
Symptoms should be cleared with providing supportive measures after discontinuing the Cizumab therapy and PRES should be monitored by undergoing MRI. In severe condition, patients should be discontinuing with Cizumab treatment.
In renal injury & Proteinuria:
Toxicity grade should be resolved by monitoring the renal function and Proteinuria.
In severe infusion reactions, patients should not take Cizumab treatment.
Embryo fetal damage:
Cizumab is contraindicated to pregnancy condition, produce fetal harm.
Cizumab receiving patients may have a chance of getting ovarian failure.
Congestive heart failure:
In anthracycline based chemotherapy, Cizumab treatment should not be used. Cizumab treatment should be discontinuing while CHF occurs.
Drug- drug interaction
Cizumab combined with paclitaxel & carboplatin causes reducing exposure of paclitaxel after completion of 4 cycles of therapy. When patients receiving paclitaxel & carboplatin as alone, causes elevation of paclitaxel exposure at day 63.