In the SMARTE-R-CHOP14 trial, rituximab 375 mg/m2 was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone on a 14 day schedule (6 x R-CHOP14), on days -4, 0, 10, 29, 57, 99, 155 and 239.
Pharmacokinetics and outcome were to be compared with those of patients who had received 6 x R-CHOP14 in combination with eight 2 week applications of rituximab in the RICOVER-60 (Rituximab with CHOP over age 60 years) trial.
The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good prognosis patients (International Prognostic index (IPI), 1 or 2, and 81% for 99 poor prognosis patients (IPI, 3 to 5); 3-year event free survival (EFS) was 71%, 75% and 67% respectively; and 3-year overall survival (OS) was 84%, 88% and 80% respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n 183; poor prognosis, n 123) revealed no outcome differences for all and good-prognosis patients; however the longer exposure time in SMARTE-R-CHOP14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54% and OS (80% v 67%) in poor-prognosis patients.r
© JCO 2014
© JCO 2014
Toxicity was not higher in SMARTE-R-CHOP14 compared with RICOVER-60; indeed, rate of leukocytopenia was considerably lower and rate of grade 3 and 4 infections was significantly lower in SMARTE-R. The latter is not likely to have been only the result of the different rituximab schedule or pharmacokinetics; rather, prophylaxes with acyclovir and cotrimoxazole likely also played a role; these were mandatory only in the SMARTE-R trial after they were shown to significantly reduce infections in the DENSE-R study, 6 where they were introduced for the first time.
European Society of medical Oncology guidelines recommend 8 x R-CHOP14x 2R for the treatment of elderly patients with DLBCL 17 because they have equal efficacy and (acute) toxicity features. The results of SMARTE-R, a large phase II study with 189 patients, strongly suggest that outcome with R-CHOP14 can be improved with modified rituximab schedule with no increase in toxicity or cost, resulting in the best results ever reported for elderly patients with DLBCL to date.r