On 18 thMay 2017, in a letterto the Editor of Blood, Caroline Gayfrom the Service de Pharmacie, Centre Hospitalier Universitaire (CHU) de Rennes, Rennes, France, and colleagues reported on their study which aimed to assess the effect of doxorubicin dose capping in DLBCL patients.
Recently, there has been uncertainty of the toxicity that arises with high doses of anthracycline therapy in patients with elevated Body Surface Area (BSA). To determine this, an analysis of 1,384 patients with DLBCL receiving first-line treatment who enrolled in four different clinical trials (LNH98-5, LNH-75, LNH03-2B, and LNH03-6B) was carried out.
All patients had been administered R-CHOP or an R-CHOP-like (mainly R-ACVBP) regimen. Using Mosteller’s formula, a theoretical BSA was estimated for each patient based on their height and weight at study inclusion. By comparing the theoretical dose (planned protocol dose) and observed dose (what the patient actually received), it could be determined if dose capping had taken place. The cutoff value for BSA was 2.1m 2.
- Pts with BSA of >2.1m 2and doxorubicin dose capped at a BSA of 2m 2received <95% of theoretical dose
- Cohort split into 3 groups:
- BSA <2.1 m 2(n=1,232; 89%) – theoretical BSA and observed BSA <2.1 m 2
- Capped BSA ≥1m 2(n=119, 8.6%) – theoretical BSA ≥2.1m 2and observed BSA <2.1 m 2
- Uncapped BSA ≥1 m 2(n=33; 2.4%) – theoretical BSA and observed BSA ≥2.1m 2
- BSA <2.1 m
2group vs. capped BSA ≥1m
2group vs. uncapped BSA ≥2.1m
- >60 years old: 75% vs. 55.5% vs. 51.5% ( P< 0.001)
- BMI <25kg/m 2: 58.8% vs. 3.4% vs. 9.1% ( P< 0.001)
- Female: 49.3% vs. 10.1% vs. 6.1% ( P< 0.001)
- aaIPI score >1: 47% vs. 37.8% vs. 30.3% ( P< 0.001)
- More B symptoms: 36.2% vs. 20.2% vs. 18.2% ( P< 0.001)
- Treatment related mortality: 3.9% vs. 6.7% vs. 6.1% ( P= 0.293)
- Median PFS (months) = 78.7 (95% CI, 64.6–91.4) vs. 75.9 (95% CI, 49.7–NA) vs. 57.9 (13.5–NA; P= 0.481)
- Median OS (months) = 106.5 (95% CI, 93.1–117.9) vs. 113.1 (95% CI, 75.9–NA) vs. 93.1 (95% CI, 32.6–NA; P= 0.864)
The letter concluded by stating that capping doxorubicin dose at 2m 2did not result in inferior efficacy in patients with DLBCL and elevated BSA. In addition, uncapped doses did not result in an increased incidence of treatment related mortality. Thus, uncapped or capped doxorubicin appears acceptable in patients with DLBCL and elevated BSA.
However, the authors cautioned readers when interpreting their results due to a few limitations of the study, such as its unplanned retrospective nature and its small sample size.