What is AUC in carboplatin dosing?
AUC values of 4 to 6 and 6 to 8 mg/mL. min gave rise to manageable hematological toxicity in previously treated and untreated patients, respectively, and hence target AUC values of 5 and 7 mg/mL min are recommended for single-agent carboplatin in these patient groups.
What does AUC mean in chemotherapy?
The most relevant pharmacokinetic parameter for drug exposure is the area under the curve (AUC) of plasma concentration x time following a single dose. During drug development, drug level sampling at multiple time points helps define the relationship between drug administration and the AUC.
Why is carboplatin dosed as AUC?
The FDA has recommended that physicians consider capping the dose of carboplatin for desired exposure (AUC) to avoid potential toxicity due to overdosing. The maximum dose is based on a GFR estimate that is capped at 125 mL/min for patients with normal renal function.
How is AUC oncology calculated?
This formula can be used to calculate the carboplatin dose accurately in order to obtain a target AUC by using only the GFR. The formula is: dose (mg) = AUC (mg ml-1 min) x [GFR (ml/min) + 25 (ml/min)].
What does the AUC tell you?
AUC represents the probability that a random positive (green) example is positioned to the right of a random negative (red) example. AUC ranges in value from 0 to 1. A model whose predictions are 100% wrong has an AUC of 0.0; one whose predictions are 100% correct has an AUC of 1.0.
What is a good AUC score?
A model with an AUC score of less than 0.7 is bad, and anything more is either adequate or better. It's vital to remember that what constitutes an “excellent” AUC score differs per industry. For example, researchers aim for AUC ratings above 0.95 because the risk of being incorrect is so great in medical contexts.
What does increased AUC mean?
The AUC is directly proportional to the dose when the drug follows linear kinetics. The AUC is inversely proportional to the clearance of the drug. That is, the higher the clearance, the less time the drug spends in the systemic circulation and the faster the decline in the plasma drug concentration.
Why is AUC dosing used?
Purpose. The area under the curve (AUC) is commonly used to assess the extent of exposure of a drug. The same concept can be applied to generally assess pharmacodynamic responses and the deviation of a signal from its baseline value.
What is AUC based dosing?
AUC vancomycin dosing represents the total vancomycin concentration in the blood over a period of time, usually over 24 hours. In order to calculate this manually: Two vancomycin levels need to be drawn when the patient's vancomycin is at a stable concentration, usually referred to as steady-state.
How is total AUC calculated?
1:238:53How to Calculate AUC - YouTubeYouTubeStart of suggested clipEnd of suggested clipWe arrive at dose over volume times the integral of the exponential. This is a solvable integral.MoreWe arrive at dose over volume times the integral of the exponential. This is a solvable integral. And can be represented by 1 over the quantity clearance.
What are the side effects of carboplatin?
Carboplatin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:nausea.vomiting.diarrhea.constipation.sores in the mouth and throat.pain, burning, or tingling in the hands or feet.More items...•
How are chemo doses calculated?
DOSE CALCULATIONS Chemotherapy drug doses are often given as the amount of drug per Body Surface Area, or BSA. The units of BSA are per square millimeter, or “mm2”, or (more properly) “mm2“. BSA is calculated from a formula that employs the height and weight of the child.
What does high AUC mean?
The Area Under the Curve (AUC) is the measure of the ability of a classifier to distinguish between classes and is used as a summary of the ROC curve. The higher the AUC, the better the performance of the model at distinguishing between the positive and negative classes.
What does increased AUC mean?
The AUC is directly proportional to the dose when the drug follows linear kinetics. The AUC is inversely proportional to the clearance of the drug. That is, the higher the clearance, the less time the drug spends in the systemic circulation and the faster the decline in the plasma drug concentration.
What does AUC represent in pharmacokinetics?
Definition. A common use of the term “area under the curve” (AUC) is found in pharmacokinetic literature. It represents the area under the plasma concentration curve, also called the plasma concentration-time profile.
What are the units of AUC?
The units of the AUC are the units of the Y axis times units of the X axis. For example, if your Y axis measures concentration in mmol/L and the X axis measures time in minutes, then the area is expressed in units of (mmol/L) x minutes.
What is the Cockcroft and Gault equation?
The original Cockcroft and Gault equation utilized total body weight , however, the most commonly used version of this equation incorporates the Ideal body weight (IBW) or an adjusted body weight (ABW) in obese patients whose actual weight is significantly greater than their IBW. Ideal body weight (IBW):
Does fluctuating creatinine level provide accurate CRCl?
2) Fluctuating serum creatinine values DO NOT provide an accurate CrCl estimate.
Who is behind the development of carboplatin?
But it’s not only the sums that have made a difference – Professor Calvert and his Cancer Research UK-funded colleagues are behind the development of carboplatin itself – a drug that has been used to treat thousands upon thousands of patients in the UK, and many more around the world. In this post, we’ll look at the birth ...
When was Calvert approved?
It was finally licensed for use across the UK in 1986 , and has gone on to become the ‘gold standard’ treatment for ovarian cancer, as well as being used to treat many other cancers. And the Calvert formula goes hand-in-hand with its clinical usefulness.
How many patients did Calvert test?
Calvert and his team then tested their formula in a further 31 patients, to see how well it held up in ‘real life’. To do this, they measured GFR in the patients then gave them doses of carboplatin. Using the formula, the researchers were able to predict the level of carboplatin that they would expect to see in the patients, and compare these predictions to actual measurements of the drug in the blood.
What is the Calvert formula?
This time, we take a look at the history of the Calvert formula – a mathematical equation used by doctors all over the world to calculate the required dose of the life-saving cancer drug carboplatin. Professor Hilary Calvert, whose eponymous formula has helped to save thousands of lives. One way to gain immortality – at least as a scientist – is ...
What is the new kid on the chemotherapy block?
Background: From cisplatin to carboplatin. At the start of the 1980s, the new kid on the chemotherapy block was a drug called cisplatin – a small molecule containing a single atom of the metal platinum. In the early 1970s, our researchers were among the first to show that the cisplatin had the potential to treat cancer.
Who was the first person to study the anti-cancer properties of cisplatin?
Leading the way were our scientists: Professor Tom Connors – one of the first people to look at the anti-cancer properties of cisplatin – Hilary Calvert, Ken Harrap and their colleagues at The Institute of Cancer Research in Sutton, working together with the pharmaceutical company Johnson Matthey.
Is carboplatin still used?
Clinical trials involving carboplatin are still going on today, testing it in combination with other drugs and in different cancer types. It is arguably one of our most powerful weapons against cancer, and its story far from over.
How often is carboplatin AUC 5 used?
Carboplatin AUC 5 IV on day 1 in combination with etoposide (120 mg/m2/day IV on days 1 through 3) and bleomycin (30 international units on day 2), repeated every 21 days for 4 cycles has been used. In a randomized trial, the combination of carboplatin (AUC 5), etoposide, and bleomycin (CEB) was compared with the standard regimen of bleomycin, etoposide, and cisplatin (BEP) in patients with good-prognosis, metastatic testicular cancer. The combination containing carboplatin resulted in a significantly lower response rate than the cisplatin-containing regimen (87.3% vs. 94.4%, respectively).
How long does carboplatin AUC 6 last?
Carboplatin AUC 6 IV in combination with paclitaxel (200 mg/m2) IV on day 1 given every 21 days produced an overall survival of 12.3 months in a phase 3 comparison of 4 chemotherapy doublets in advanced NSCLC. In another similar 4-arm phase 3 comparison, carboplatin AUC 6 IV on day 1 in combination with paclitaxel 225 mg/m2 IV on day 1 given every 21 days, produced an overall survival of 7.8 months, which was similar to the reference regimen of cisplatin and paclitaxel.
How does carboplatin affect DNA replication?
Carboplatin cytotoxic activity is similar to cisplatin as it binds with DNA to form intrastrand crosslinks and adducts that cause changes in the conformation of the DNA and affect DNA replication. Carboplatin readily crosses the cell membrane. Once inside the cell, the ring structure of carboplatin is hydroxylated by water to form the active moiety. This reaction occurs more slowly than the activation of cisplatin. Therefore, 4—6 times the amount of carboplatin is required to produce the same cytotoxic effects as cisplatin. Once in the active form, carboplatin functions similarly to cisplatin and binds with DNA, RNA, or other macromolecules at two sites to form interstrand and intrastrand links. Carboplatin forms irreversible covalent bonds which inhibit DNA replication, RNA transcription, and protein synthesis. Intrastrand crosslinks at the N7 position of guanine are the predominant binding sites. The maximal DNA crosslinks occur 18 hours after exposure to carboplatin compared to 6—12 hours for cisplatin. Carboplatin crosslinks have a slower removal rate than do cisplatin-induced crosslinks. This slower rate of onset and removal of carboplatin crosslinks is thought to be due to a slow rate of monofunctional adduct formation and/or a slower rate of conversion of monoadducts to crosslinks. While considered cell cycle non-specific, carboplatin cytotoxicity is increased with exposure during the S-phase and with increased infusion rates (24 hours versus 1 hour). Carboplatin causes cell cycle arrest in the G2-phase and then induces programmed cell death or apoptosis.
How much carboplatin is in ifosfamide?
Adults. Ifosfamide 0 to 10 g/m2 IV in 4 divided doses on days -6 to -3, in combination with carboplatin 1,500 to 2,000 mg/m2 IV in 3 divided doses on days -6 to -4 (1,500 mg/m2) or in 4 divided doses on days -6 to -3 (more than 1,500 mg/m2), and etoposide 1,200 to 2,400 mg/m2 IV in 4 divided doses on days -6 to -3.
What is the AUC 6 IV?
AUC 6 IV in combination with docetaxel (75 mg/m2 IV) on day 1 given every 21 days for 4 to 6 cycles. In a phase 3 trial of 1,203 patients with unresectable locally advanced or metastatic NSCLC, docetaxel and platinum combinations (cisplatin or carboplatin) were compared with cisplatin/vinorelbine. No difference was observed between docetaxel/carboplatin and cisplatin/vinorelbine in overall survival, the primary endpoint. Grade 3 and 4 anemia and nausea/vomiting were significantly lower in both docetaxel containing arms. In addition, hospitalizations and treatment discontinuation secondary to toxicity were higher with cisplatin/vinorelbine. A separate phase 3 trial conducted in 422 patients with inoperable, locally advanced or metastatic NSCLC compared docetaxel/carboplatin to mitomycin C/cisplatin plus either ifosfamide or vinblastine. The primary endpoint, 1-year overall survival, was not significantly different between the treatment arms. Grade 3 and 4 neutropenia, infection, and mucositis were all significantly higher with docetaxel/carboplatin, while quality of life scores were significantly better.
What is the maximum tolerated dose of carboplatin?
The suggested maximum tolerated dose (MTD) for carboplatin is dependent on performance status, other chemotherapy agents or radiation given in combination, and disease state. The dosing of carboplatin may vary from protocol to protocol. If questions arise, clinicians should consult the appropriate references to verify the dose.
Can carboplatin be used for ovarian cancer?
NOTE: Recommendations are only available for the initial course of treatment for ovarian cancer with carboplatin as a single agent or with cyclophosphamide. Subsequent adjustments should be done base on the toxicity of the previous course.
