Carboplatin is a chemotherapy drug from the group of second-generation platinum drugs, which are also classified as alkylating agents. This is one of the most common groups of chemotherapy drugs; they are used for many cancer diseases. This treatment is often called "platinum chemotherapy."
Other platinum drugs: cisplatin, oxaliplatin, lipoplatin, satraplatin, nedaplatin, picoplatin, cycloplatam, triplatin tetranitrate.
Carboplatin is marketed under the commercial name Paraplatin. Let's talk about what types of cancer this drug is used for, how it is treated, what side effects are possible, and how they can be prevented and controlled.
Pharmacological properties of the drug Carboplatin
Antitumor agent. It is an inorganic complex compound of platinum. The mechanism of action is due to interaction with DNA with the formation of intra- and interhelical cross-links, which change the structure of DNA and suppress its synthesis. After intravenous administration for 1 hour, the pharmacokinetic parameters of free and total platinum are described by a two-phase pharmacokinetic model. Protein binding in the first 4 hours is 29%, after 24 hours it is 85–89%. Basically (up to 32% of the dose) is excreted unchanged in the urine. For free platinum, the half-life in the initial phase is about 90 minutes, and in the terminal phase - about 60 hours. The half-life of total platinum in the initial phase coincides with this indicator for free platinum, but in the terminal phase it can exceed 24 hours.
How does carboplatin destroy cancer cells?
Among all platinum drugs, the mechanism of action of cisplatin is the best studied. Carboplatin is thought to act in much the same way. It binds to DNA, promotes the formation of cross-links within the helix and between chains, between DNA and protein molecules. Because of this, damaged DNA cannot be repaired and its replication (synthesis of new DNA), which is necessary for cell division, is disrupted. The cancer cell stops reproducing, and apoptosis—programmed cell death—starts.
Use of the drug Carboplatin
Carboplatin is administered only intravenously through a short infusion over 15–60 minutes. Pre-dissolve in 5% glucose solution or 0.9% sodium chloride solution to a final concentration of 0.5 mg/ml. Adults with normal renal function who have not previously received treatment are administered at a dose of 400 mg per 1 m2 of body surface over 15–60 minutes. The course of therapy can be repeated no earlier than after 4 weeks. In patients receiving drugs that have a myelosuppressive effect, in patients after radiation therapy, as well as in people in serious condition, the initial dose should be 300–320 mg/m2. In patients over 65 years of age, the dose of carboplatin should be adjusted taking into account their general condition. For patients with increased risk factors (testicular tumors and metastatic breast cancer), a high therapeutic dose of 1200–2100 mg/m2 (followed by bone marrow transplantation) can be administered as a long-term infusion; infusion time is 1–24 hours depending on the chemotherapy regimen. In patients with impaired renal function (creatinine clearance less than 60 ml/min), the dose of carboplatin should be reduced and adapted to the level of glomerular filtration.
How is treatment carried out?
Carboplatin is administered intravenously in different ways:
- Through an IV.
- Through a central venous catheter.
- Through the infusion port system. It is a small container shaped like a coin. One of the walls of this tank is represented by a membrane made of polymer material. The doctor makes an incision in the skin, places a reservoir inside and connects it with a catheter to the vein. The wound is sutured. Subsequently, when the drug needs to be administered, the skin with the membrane is pierced with a special needle. Typically, infusion port systems are used in patients who require long-term treatment.
The drug administration procedure lasts about an hour.
Carboplatin chemotherapy is given in cycles. The patient is administered the drug, after which they take a break of 3-4 weeks - this is the duration of the cycle. Such “breathes” are needed so that the body can recover - after all, chemotherapy drugs damage not only cancer cells, but also rapidly multiplying healthy cells.
Typically, the course of treatment consists of 4–6 cycles.
It is important to correctly calculate the dosage and schedule of administration of the chemotherapy drug. The attending physician must take into account the patient’s height and weight, general health, concomitant diseases, and individual tolerance.
Sometimes, for example, for ovarian cancer, carboplatin is administered intraperitoneally - through a puncture in the abdominal wall.
Information for healthcare professionals
On average, carboplatin remains in the blood for 3.5 hours.
The concentration of platinum in the drug molecule in the blood plasma significantly exceeds its concentration in free form.
Carboplatin binds to plasma proteins and leaves the body for a long time, mainly through the kidneys. Its half-life is at least 5 days. In patients with a creatinine clearance (CC) of 60 ml/min or more, approximately 70% of the administered dosage is excreted in urine after 12–16 hours. Platinum is found in carboplatin in 24-hour urine, and only 3 to 5% of the administered dosage is excreted in the urine after 24 to 96 hours. As CC decreases, renal clearance of the drug also decreases. Therefore, in patients with CC less than 60 ml/min, carboplatin dosages should be reduced.
Side effects of the drug Carboplatin
Leukopenia, thrombocytopenia, anemia; increased concentrations of creatinine, urea, uric acid in the blood plasma; nausea, vomiting (may develop 6–12 hours after administration and usually disappear within 24 hours), diarrhea, constipation, increased activity of liver enzymes; paresthesia, decreased deep tendon reflexes, decreased hearing in the high frequency range; disturbances of water and electrolyte balance (hypomagnesemia, hypokalemia, hypocalcemia); allergic reactions (erythematous rash, itching, fever); alopecia, flu-like syndrome, reactions at the injection site.
Methods of administration
The effectiveness and toxicity of carboplatin are determined not only by the dose administered, but also by the rate of its elimination from the body. Therefore, unlike all other anticancer drugs, its dose is calculated not in milligrams per patient’s body area, but according to a formula that involves blood creatinine, determined by a biochemical blood test. The level of creatinine determines the ability of the kidneys to eliminate toxins.
The platinum drug in the calculated dose is administered intravenously by drip from a quarter of an hour to an hour and can even be administered throughout the day by an infusion pump. A single dose can be administered at a time or divided into 3-5 days, the course is repeated after 3-4 weeks. In case of toxic damage to the blood and kidneys, the dose of the drug can be reduced by a quarter.
Special instructions for the use of the drug Carboplatin
Treatment with carboplatin can only be carried out by specialists with experience in therapy with cytotoxic drugs. The drug is prescribed with caution to patients with impaired renal function. In this category of patients, as well as in elderly people, patients who have previously received chemotherapy, and with prolonged immobilization of patients, the risk of myelotoxicity is increased. In these cases, the dose should be reduced and the composition of peripheral blood should be carefully monitored. The maximum decrease in platelet levels usually occurs between 14 and 21 days after the start of treatment, and in leukocytes - between 14 and 28 days. The minimum level should be: for platelets - 50,000 per 1 mm3, for leukocytes - 2000 per 1 mm3. If the cell count is below this level, then therapy should be suspended until normal values are restored (usually 5-6 weeks). In severe cases, maintenance transfusion therapy may be required. To avoid profound myelosuppression, repeated courses of carboplatin treatment should not be repeated under normal conditions more than once a month. Neurological examination and monitoring of hearing function should be performed regularly during and after treatment with carboplatin. Women of childbearing potential receiving carboplatin should use reliable contraception. Carboplatin has mutagenic, embryotoxic and teratogenic effects. Personnel should take special precautions when handling carboplatin.
Introduction
Lung cancer is the most common cause of death from cancer in men.
About 80% of lung cancer cases are non-small cell lung cancer (NSCLC). Up to 60% of NSCLC patients have stages IIIb (locally advanced NSCLC) and IV (metastatic NSCLC) at the time of diagnosis. Since NSCLC at these stages is an incurable disease, the goal of therapy in these patients is to maximize life expectancy and improve its quality [1, 2, 6, 7]. The combination of paclitaxel and carboplatin is one of the main combination chemotherapy regimens used in the first line of treatment of advanced NSCLC [1, 3, 7, 10]. Taking into account the high cost of these drugs, the question of the therapeutic equivalence of imported and more affordable domestic chemotherapy drugs is of considerable interest.
In 2009, a clinical trial of the drugs Taxacad (paclitaxel) and Carboplatin began, in which the assessment of safety and effectiveness is carried out in accordance with international criteria. The drugs Taxacad and Carboplatin are produced by Biocad CJSC (Russia) from substances of its own production in a modern plant that complies with GMP (Good Manufacturing Practice) standards.
This paper presents the interim results of a study assessing the safety and effectiveness of therapy with Taxacad and carboplatin in patients with stage III–IV NSCLC.
Material and methods
47 patients from 8 centers were screened for the open multicenter clinical trial.
To be included in the study, the patient had to meet the following criteria:
- age at least 18 years;
- providing written informed consent;
- confirmed diagnosis of NSCLC stages III–IV;
- presence of measurable foci of disease;
- ECOG (Eastern Oncology Cooperative Group) index value 0–1 point inclusive;
- life expectancy greater than 20 weeks;
- the level of bilirubin is less than 25.7, creatinine is less than 133.0 µmol/l, transaminases are not higher than three times the maximum normal values (in the presence of metastases in the liver - no higher than five times).
The patient was not eligible for inclusion in the study in the following cases:
- carrying out cytostatic therapy before inclusion in the study;
- neutropenia;
- thrombocytopenia;
- presence of signs of peripheral neuropathy of the second or higher degrees;
- metastatic brain damage;
- the presence of diseases that can affect the assessment of the severity of symptoms of the underlying disease;
- the presence of other malignant diseases noted over the past 5 years;
- presence of signs of chronic renal failure;
- presence of signs of epilepsy or a convulsive syndrome of another origin in the anamnesis;
- any acute or active chronic infections;
- any signs of mental illness;
- a history of allergies to substances included in the study drugs (Taxacad, Carboplatin);
- drug addiction, alcoholism, HIV infection;
- simultaneous participation in other clinical trials;
- the presence of obstacles to the administration of chemotherapy drugs in the form of intravenous infusions.
Due to non-compliance with inclusion criteria, two patients dropped out of screening. One patient dropped out before the administration of study drugs due to the development of acute myocardial infarction. One patient withdrew his consent to participate in the study before administration of the study drugs. Within 2 weeks after inclusion in the study, one patient had brain metastases, and two had clinical signs of rapid disease progression, which was regarded as non-compliance with the inclusion criteria and resulted in discontinuation of participation in the study.
Therefore, the analysis included 40 patients (31 men and 9 women) who met the study inclusion criteria and received at least one dose of Taxacad and Carboplatin. The average age of the patients was 58 years (range 34 to 74 years).
In this study, Taxacad and Carboplatin, pharmaceutically equivalent to the original drugs, were used. On the first day of each cycle, patients included in the study received Taxacad at a dose of 175 mg/m2 as a 3-hour intravenous infusion after standard premedication, followed by a 30-minute intravenous infusion of Carboplatin at a dose corresponding to AUC = 6. The cycles were repeated. every 21 days.
With the development of grades III–IV neutropenia and/or febrile neutropenia after chemotherapy, a course of daily subcutaneous injections of the granulocyte colony-stimulating factor (G-CSF) drug Leukostim (filgrastim, Biocad, Russia) was prescribed at a dose of 5 mcg/kg/day until the number of neutrophils reached > 2 × 109/l.
The antitumor effect was assessed based on RECIST criteria (Response Evaluation Criteria in Solid Tumors) after the 3rd and 6th courses of chemotherapy. Further evaluation of the effectiveness of therapy in these patients was carried out 6, 9 and 12 months after the start of treatment.
The first step at the statistical processing stage was to determine the type of features available and the nature of their distribution. To describe quantitative continuous characteristics, the distribution of which corresponded to the law of normal distribution, the mean value (M), standard deviation (SD) and/or 95% confidence interval (CI) were used. To describe qualitative ordinal characteristics, the median (Me) and interquartile range (25–75%) were used.
results
20.0% of patients were diagnosed with stage IIIa NSCLC, 12.5% with stage IIIb, and the majority (65.0%) of patients with stage IV. Most patients were diagnosed with multiple distant metastases: pleura – 3 cases, liver – 4, adrenal glands – 5, kidneys – 2, bones and spine – 6, distant lymph nodes – 5; damage to the other lung occurred in 12 cases, metastases to the ipsilateral lobe - in 7.
From 1 to 6 cycles of chemotherapy were carried out (1 course - 2 patients, 2 courses - 3, 3 courses - 12, 4 courses - 1, 5 courses - 3, 6 courses - 19; in total - 177 courses). Safety data were analyzed for all patients who received at least one dose of the study drug.
The assessment of the safety and tolerability of the drugs Taxacad and Carboplatin was based on data on the frequency and severity of side effects of chemotherapy, including deviations in clinical and biochemical blood tests (according to the NCI CTC - National Cancer Institute-Common Toxicity Criteria, version 2.0.), results of assessment of general somatic status according to the Karnofsky scale as modified by ECOG and assessment of neurological status. Data on toxicity assessment based on laboratory parameters are presented in table. 1.
. Overall toxicity (proportion of patients who experienced these changes).
During the entire observation period, grade III anemia was observed in 5% of patients; there were no cases of grade IV anemia. A transient decrease in the number of leukocytes was noted to a level corresponding to grades I–II toxicity in 60% of patients. Only 10% of patients had grade III leukopenia. There were no cases of grade IV leukopenia. There was a transient decrease in the number of neutrophils to the level of I–II degrees of toxicity in 35% of patients, and in 40% of patients neutropenia of III–IV degrees was noted. However, only 35% of cases required the administration of G-CSF. The proportion of patients who experienced grades III–IV neutropenia reached 29.2% by the 4th course of chemotherapy (Fig. 1). Thrombocytopenia of III degree (without clinical manifestations) was registered in 2.5% of cases. There were no cases of severe thrombocytopenia grade IV.
Laboratory studies did not reveal a single case of severe hepatic-renal toxicity. The NCI CTC toxicity criteria, version 2.0, were also used to assess the severity of peripheral neuropathy, one of the most common side effects of paclitaxel and carboplatin. During screening (before the start of treatment), signs of peripheral neuropathy were absent in all patients. In total, during the observation period, the development of neuropathy of degrees I–II was noted in 25% of cases; cases of the development of severe forms (grades III–IV) were not registered.
General somatic status was assessed using the ECOG scale. When screening before treatment, the ECOG score was 0 in 16 (40%) patients and 1 in 24 (60%). After 3 courses of chemotherapy (day 64), data are available for 35 patients. The ECOG score was 0 in 12 (34.3%) patients, 1 in 19 (54.2%), 2 in 3 (8.6%) and 3 in 1 (2.9%). After 6 courses of chemotherapy (day 126, data available for 19 patients), the ECOG score was 0 in 3 (15.8%) patients, 1 in 15 (78.9%) and 3 in 1 (5 .3%). Deterioration of general somatic status according to the ECOG scale was associated with progression of the underlying disease or concomitant pathology.
One serious side effect has been reported: cardiomyopathy due to anemia after 4 cycles of chemotherapy, resulting in death. A relationship with the study treatment was assessed by the investigator as unlikely.
In addition, the following side effects were observed (in addition to the laboratory abnormalities described above):
- 50% (n = 20) of patients had alopecia of degrees II–III; relationship with study therapy was assessed as probable;
- 17.5% (n = 7) of patients had cases of myalgia, arthralgia and ossalgia of mild to moderate severity; assessed by investigators as related to drug intake;
- 15% (n = 6) of patients had episodes of mild to moderate asthenia; assessed by investigators as related to drug intake;
- 10% of patients (n = 4) experienced mild to moderate nausea, sometimes accompanied by vomiting; assessed by researchers as drug-related;
- 10% (n = 4) experienced allergic reactions (eosinophilia, Quincke's edema, reactions during infusion); were assessed by the researchers as being related to the drug. Two patients dropped out of the study due to the development of these side effects;
- 17.5% (n = 7) of patients had pain of various localizations, which was regarded by the researchers as not related to the study therapy. Most likely, the pain was caused by manifestations of the underlying disease;
- 10% (n = 4) had shortness of breath, cough, and hemoptysis, which, in the opinion of the researcher, were not related to taking the drug;
- 1 (2.5%) case of bilateral fungal pneumonia was registered. Considered by the investigators to be unrelated to the study drugs and not a serious side effect that did not affect the regimen/dose of the study drugs. Pneumonia was completely cured as a result of antimycotic therapy;
- in 1 (2.5%) case, leukocyturia was observed 20 days after the start of therapy. Considered by investigators to be unrelated to drug intake. Completely relieved by antibacterial therapy;
- in 1 (2.5%) case, febrile temperature was observed even before the start of treatment and persisted throughout the entire observation period. Considered by investigators to be unrelated to study therapy.
To evaluate the effectiveness, computed tomography with contrast was performed. Evaluation of the effectiveness of the treatment based on RECIST criteria was performed in 35 patients; 3 patients were not included in the effectiveness analysis because they dropped out before the first assessment (2 due to allergic reactions, 1 due to disease progression unconfirmed by instrumental methods); two were not included in the efficacy analysis because they were withdrawn from the study after 2 cycles of chemotherapy due to clinical deterioration, although stabilization was noted when assessed by RECIST criteria.
8 patients dropped out of the study due to verified disease progression after 2–3 cycles of chemotherapy (in 1 of 8 patients with disease progression, the assessment was carried out after 2 courses of chemotherapy due to the need to confirm clinical signs of progression), 2 patients with significant tumor regression (stabilization and partial response) after 3 courses of chemotherapy, radical surgical interventions were performed, 7 patients dropped out before re-evaluating the effectiveness (2 due to the development of side effects, 3 for reasons not related to the study drug). In 20 patients, efficacy was re-evaluated in accordance with RECIST criteria (in 19 - after 6, in 1 - after 5 courses of chemotherapy).
According to RECIST criteria, partial response was observed in 7 (20.0%) patients, stabilization in 20 (57.1%) and progression in 8 (22.9%) patients.
Discussion
In accordance with international experience in registering generic drugs based on active substances of a chemical nature, they are considered therapeutically equivalent to the original drugs if there is evidence of their pharmaceutical equivalence and bioequivalence. Pharmaceutical equivalence implies the identity of the content of the active substance and the characteristics of the dosage form of the original and generic drugs, as well as compliance of the generic drug with pharmacopoeial quality criteria. A generic drug is considered bioequivalent to the original drug if its bioavailability (the speed and extent with which the active substance is absorbed and appears in the systemic circulation) does not differ significantly from the original drug. Bioequivalence studies cannot be applied to intravenously administered drugs, since bioavailability is always 100% when administered intravenously. As a result, generic drugs administered intravenously, including most cytostatics, are approved for medical use based only on evidence of pharmaceutical equivalence obtained during the state quality examination.
However, the best evidence of therapeutic equivalence has been and remains clinical studies that assess the safety and effectiveness of the drug. Given that the combination of paclitaxel and carboplatin in NSCLC has been well studied, the scope of clinical trials of generic drugs may be limited. Thus, when conducting a clinical trial of generics using protocols whose design replicates previously conducted international multicenter studies, it is possible to compare the results obtained with retrospective data, and the sample size can be significantly reduced.
Due to the high relevance of the issue of import substitution of expensive drugs with more affordable domestic analogues and taking into account international experience in the study of generic drugs, we developed a protocol for a clinical study of the drugs Taxacad and Carboplatin, the preliminary results of which are presented in this work.
For the purpose of comparative analysis of data on the incidence and severity of side effects, we analyzed literature data [3, 4, 5, 8, 10] on the most typical side effects in patients who received from 6 to 10 cycles of combination chemotherapy with paclitaxel and carboplatin (Table 2). In addition, severe cardiotoxicity has been reported in rare cases, ranging from 0.5% [4] to 3.0% in the ECOG study [10]; stomatitis [5]; ototoxicity, including severe, in 3% of cases [8].
. Safety and toxicity profile of the combination of paclitaxel and carboplatin, according to foreign clinical studies.
Comparative data on the frequency of side effects in this and international clinical studies [5, 8] are presented in Fig. 2. Data on severe (corresponding to toxicity grades III-IV, according to NCI CTC criteria, version 2.0) hematological toxicity are presented in Fig. 3 [5, 8].
Thus, the side effects observed with the use of Taxacad and Carboplatin (alopecia, nausea, arthralgia/myalgia, asthenia, neutropenia) are expected. The frequency and severity of side effects did not exceed those recorded in international multicenter clinical studies. Moreover, the incidence of some adverse events in this study was lower compared to the literature, which may be due to the shorter duration of treatment, lower course dose of chemotherapy, and the smaller number of patients included in the study to date.
In order to evaluate the effectiveness of the drugs Taxacad and Carboplatin, we compared the results of evaluating the effectiveness according to RECIST criteria with literature data on the rate of objective response and stabilization when using similar chemotherapy regimens in the treatment of advanced NSCLC. Thus, in a study by Kosmidis P. et al. [5] the use of paclitaxel at a dose of 175 mg/m2 (as a 3-hour intravenous infusion) and carboplatin at a dose corresponding to AUC = 6 every 3 weeks allowed achieving a complete response in 6.7% of cases, a partial response in 18.9 %, stabilization – in 38.9% [5].
In a multicenter, randomized, comparative phase III clinical trial [8] using the regimen of paclitaxel 200 mg/m2 as a 3-hour intravenous infusion and carboplatin at a dose corresponding to AUC = 6, with an interval of 21 days, a complete response was achieved in 1% patients, partial – in 24%, stabilization – in 40%.
In a comparative randomized clinical trial conducted by ECOG [10], one of the groups used a regimen of paclitaxel at a dose of 225 mg/m2 as a 3-hour intravenous infusion and carboplatin at a dose corresponding to AUC = 6, with an interval of 21 days. The proportion of patients who achieved a complete response was less than 1%, partial – 19%, stabilization – 21%. In a study by Scagliotti G. et al. [9] conducted a comparative assessment of the effectiveness of three platinum-containing regimens. In 1 (n = 204) of the groups, patients received paclitaxel 225 mg/m2 and carboplatin AUC = 6 on day 1 every 3 weeks. According to the study results, the rate of achieving an objective effect and stabilization in the described group was 68.5%. In a comparative randomized phase III study conducted by the Southwest Oncology Group Trial [3], one of the groups used a similar design. After 6–10 cycles of chemotherapy, a complete response was recorded in 1% of cases, a partial response in 24%, and stabilization in 33%.
The results of a preliminary assessment of the effectiveness of Taxacad and carboplatin in terms of the overall response rate (complete and partial response; Fig. 4), as well as objective effect and stabilization (Fig. 5) are consistent with data from international multicenter clinical trials.
Conclusion
Thus, the results of this study suggest that the safety and effectiveness of combination chemotherapy based on the generic drugs Taxacad and Carboplatin are not significantly different compared to the safety and effectiveness of a similar regimen based on the original drugs paclitaxel and carboplatin.
Research into the effectiveness and safety of Taxacad and Carboplatin is currently ongoing. The goal of the second phase of the study is to study the drugs in a group of 100 patients to determine the rate of objective clinical response, progression-free survival and overall one-year survival.
It should be noted that the presented work is the first and so far the only Russian clinical study in the field of oncology that evaluates the effectiveness of domestic generic drugs in accordance with RECIST criteria.
Information about the authors: Marenich Alexander Fedorovich – senior researcher, Russian Cancer Research Center named after. N.N. Blokhin RAMS. Tel.; Reutova Elena Valerievna – Russian Cancer Research Center named after. N.N. Blokhin RAMS. Tel.; Sheveleva Lyudmila Petrovna – head of the CT department, Volgograd Regional Clinical Oncology Dispensary No. 1. 8; Karaseva Nina Alekseevna – Candidate of Medical Sciences, Head of the Thoracic Department, City Oncology Dispensary, St. Petersburg. Tel.; Bogdanova Natalya Viktorovna – head of the CTO polyclinic, Moscow Scientific Research Oncology Institute named after. P.A. Herzen Rosmedtekhnologii; Uskov Dmitry Albertovich – oncologist, Moscow Regional Oncology Dispensary of the Ministry of Health of the Moscow Region. Tel.; Khasanov Rustem Shamilevich – chief physician, Clinical Oncology Dispensary, Kazan. Tel.; Mukhametshina Guzel Zinurovna – Clinical Oncology Dispensary, Kazan; Tuzikov Sergey Aleksandrovich – Doctor of Medical Sciences, head of the department of thoracoabdominal oncology, Oncology Research Institute of the Tomsk Scientific Center of the Siberian Branch of the Russian Academy of Medical Sciences. Tel.; M iller Sergey Viktorovich – Doctor of Medical Sciences, senior researcher at the Department of Thoracoabdominal Oncology, Research Institute of Oncology, Tomsk Scientific Center of the Siberian Branch of the Russian Academy of Medical Sciences. Khorinko Andrey Vitalievich – head of the 1st chemical technical department, Perm regional oncology dispensary. Tel.
Drug interactions Carboplatin
Carboplatin reacts with aluminum-containing components of needles, syringes, catheters and IV drug sets to form a black precipitate, and therefore instruments made from such materials should not be used to administer carboplatin. The myelotoxic effect may be enhanced by the simultaneous use of carboplatin and other drugs that have myelosuppressive properties. An increase in related side effects may occur when carboplatin is combined with drugs that have ototoxic and/or nephrotoxic properties. Carboplatin should not be combined with complexing agents, as its antitumor activity may theoretically be reduced. The synergism of the action of carboplatin with etoposide and vindesine has been established.
Indications for use
“Chemotherapy with platinum” has a wide range of antitumor effects and is not used only for malignant diseases of the blood and lymphatic system. The greatest effectiveness of carboplatin was observed in ovarian and testicular cancer, and chemotherapy is called the “gold standard”.
Carboplatin is included in the main combinations of therapy for small cell and non-small cell lung cancer. It is definitely used for malignant tumors of the head and neck, cancer of the cervix and uterine body, and bladder. This is not the first-line treatment for breast cancer, but for some forms it is absolutely irreplaceable. Helps with melanoma and retinoblastoma, with sarcomas of soft tissues and bones.
Side effects after chemotherapy with platinum
Carboplatin can greatly spoil the blood picture, and not so much reduce leukocytes as platelets and red blood cells. As a rule, the maximum decrease in leukocytes and platelets is recorded after two to three weeks, and hemoglobin depends on the total dose of the drug taken orally for all courses. In some cases, the process of blood restoration is greatly delayed and replacement therapy with platelets or red blood cells may be required.
Like all platinum derivatives, the drug damages nerve endings, first causing a decrease in sensitivity, and then motor disorders. Patients should undergo dynamic audiometry - a hearing test - because the platinum derivative damages the auditory nerves and, if left unchecked, can lead to deafness. Neurotoxic damage can only manifest as long-term weakness—asthenia.
The drug causes nausea and vomiting, so the drip is preceded by taking and administering antiemetic drugs, but even after treatment, nausea and vomiting can last a day or more. Therefore, the patient is prescribed programs to reduce unpleasant consequences.
Typically, carboplatin does not cause alopecia totalis. It is not recommended to vaccinate during chemotherapy with platinum derivatives, since infection may develop when the immune system is weakened.
If you are prescribed chemotherapy with carboplatin, we will help you undergo treatment with minimal losses and a better quality of life by offering a program for preparation for the course of treatment and recovery after chemotherapy. Find out more.
