1. Carboplatin Dosing: Using Actual versus Adjusted Body Weight
Eva Y. Pan, PharmD; Nicholas Forcello, PharmD, BCPS, BCOP
1 = 2
2 = 5
3 = 4
4 = 6
Department of Pharmacy Services, Hartford Hospital, Hartford, CT
Introduction
Methods
Statistical Analysis
This retrospective study has been approved by the Institutional Review Board.
In clinical practice, there has been a tendency to under-dose obese cancer patients due to concerns of increased toxicity from higher doses of chemotherapy.
Current American Society of Clinical Oncology guidelines for dosing chemotherapy in obese adult patients recommend that actual body weight be used, as less than full weight-based doses may result in poorer disease-free survival and overall survival rates.1
Carboplatin dosing is based off of the Calvert formula, which uses the pharmacokinetic parameters of area under the curve (AUC) and drug clearance, as estimated by renal function, to determine the patient’s ideal dose in milligrams.2,3
Historically, the Gynecologic Oncology Group (GOG) has used the Jelliffe formula to calculate glomerular filtration rate (GFR) for input into the Calvert equation. However, the original Jelliffe formula calculates less precise doses for individualized therapy since it is does not factor in body weight.4
Wright et al. found that carboplatin may be under-dosed in the obese population if body weight is not accounted for in dosage calculations when using the Jelliffe formula.5
Our institution uses the 2011 GOG recommendations for calculating carboplatin doses. The Cockcroft-Gault equation is used to estimate a patient’s GFR and an adjusted body weight equation is used in patients with a BMI ≥25 kg/m2.6
Despite these recommendations, there is limited research comparing actual and adjusted body weight carboplatin dosing strategies for use within creatinine clearance calculations. Our study aims to evaluate this dosing strategy.
Group sample sizes of 120 in the BMI ≥25 group and 80 in the BMI <25 group would afford 80% power to detect a 15% difference between the groups in the primary endpoint.
Descriptive statistics will consist of mean and standard deviation for summarizing the ages and BMIs of the two groups. Differences between groups for the primary outcome will be evaluated using a Z test with pooled variance. Differences between groups for secondary outcomes will be analyzed with a chi square test or Fisher’s exact test.
Statistical analyses will be performed using SPSS or SAS, and assuming an alpha level of 0.05 such that all results yielding p<0.05 will be deemed statistically significant.
Inclusion Criteria
Exclusion Criteria
Females
≥ 18 years old
Chemotherapy-naïve patients with a gynecologic malignancy who received their first cycle of chemotherapy at Hartford Hospital from January 1, 2006 to July 1, 2015 with a regimen of carboplatin and paclitaxel or carboplatin and docetaxel dosed every 21 days with or without bevacizumab
Males
<18 years old
End-stage renal disease (defined as patients receiving dialysis)
Prior malignancies
Prescribed carboplatin dose < or > 5% of the calculated dose based on current GOG recommendations
Dose reductions for cycle 1
Patients will be stratified according to BMI (BMI <25, BMI ≥25).
Carboplatin activity will be observed by measuring the mean percent decrease in platelet count following the first cycle of chemotherapy.
Other variables to be collected: carboplatin AUC desired, carboplatin dose administered, paclitaxel dose administered (mg/m2 and total dose), docetaxel dose administered (mg/m2 total dose), dosage caps based on body surface area, patient height and weight, serum creatinine, and past medical history for the purposes of meeting inclusion and exclusion criteria.
Interim Results
632 patients to be evaluated
278 excluded
96 included
BMI < patients: Mean % decrease in platelet count = 11.03%
BMI ≥ patients: Mean % decrease in platelet count = 14.68%
258 yet to be evaluated
Primary Endpoint
Mean percent decrease in platelet count for each group from baseline until prior to cycle 2
Secondary Endpoints
Any grade 2, 3, or 4 thrombocytopenia throughout all cycles of chemotherapy, according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0 7
Grade 1 thrombocytopenia: <LLN – 75,000 platelets/mm3
Grade 2: <75,000 – 50,000/mm3
Grade 3: <50,000 – 25,000/mm3
Grade 4: <25,000/mm3
Grade 5: death
All Patients
Thrombocytopenia
Neutropenia
Any grade 2, 3, or 4 neutropenia throughout all cycles of chemotherapy, according to CTCAE v4.0
Grade 1 neutropenia: <LLN – 1500 neutrophils/mm3
Grade 2: < /mm3
Grade 3: < /mm3
Grade 4: <500/mm3
Grade 5: death
References
Objective
Griggs JJ, Mangu PB, Anderson H, et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2012; 30:
Calvert AH, Newell DR, Gumbrell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 1989; 7:
Collins IM, Roberts-Thomson R, Faulkner D, et al. Carboplatin dosing in ovarian cancer: problems and pitfalls. Int J Gynecol Cancer 2011; 21:
Okamoto H, Nagatomo A, Kunitoh H, et al. Prediction of carboplatin clearance calculated by patient characteristics or 24-hr creatinine clearance: a comparison of the performance of three formulae. Cancer Chemother Pharmacol 1998; 42:
Wright JD, Tian C, Mutch DG, et al. Carboplatin dosing in obese women with ovarian cancer: a Gynecologic Oncology Group study. Gynecol Oncol 2008; 109:
DiSaia PJ, Copeland LJ. Updated FAQ’s for dosing of carboplatin. Gynecologic Oncology Group Newsletter. 2011; Spring: 2-4.
National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0. Retrieved from
To evaluate if there is a difference in carboplatin activity between patients with a BMI <25 kg/m2 dosed based on actual body weight, and those with a BMI ≥25 kg/m2 dosed based on adjusted body weight.
Authors of this presentation have the following to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation:
Eva Pan has nothing to disclose; Nicholas Forcello has nothing to disclose.