For patients with relapsed or refractory aggressive lymphoma in a National Cancer Institute of Canada clinical trial, second-line treatment with GDP (gemcitabine, dexamethasone, and cisplatin) was as effective as DHAP (dexamethasone, cytarabine, and cisplatin). Treatment with GDP “can be considered the preferred treatment option for these patients,” Michael Crump, MD, of Princess Margaret Cancer Center in Toronto and colleagues concluded in the Journal of Clinical Oncology.
The trial “tested the hypothesis that comparable efficacy could be achieved with GDP and that this treatment, administered on an outpatient basis, would be associated with fewer adverse events and less frequent hospitalization compared with DHAP,” the authors wrote. “Our trial is the largest randomized comparison of second-line chemotherapy regimens administered before autologous stem-cell transplantation, to our knowledge, and the results confirmed our hypothesis.”
Most of the patients in the study had stage III or IV and high intermediate-risk or high-risk disease at random assignment to GDP or DHAP. Moreover, most patients “had either not achieved a remission with initial therapy or had recurrence of lymphoma within 1 year of completing treatment,” the authors noted.
Among the 619 intention-to-treat patients, 71% had diffuse large B-cell lymphoma, 15% had lymphoma that had transformed from an indolent B-cell histology, and 8% had T-cell or anaplastic large cell lymphoma. Among 554 B-cell lymphoma patients, 411 had previously been given rituximab (Rituxan). Patients with B-cell lymphoma also received rituximab along with GDP or DHAP. Patients who responded proceeded to stem cell collection and autologous stem cell transplantation.
The two primary endpoints of the study were response rate after two treatment cycles, with the noninferiority margin for the response rate to GDP relative to DHAP set at 10%, and transplantation rate. Among the intention-to-treat population, “the response rate with GDP was 45.2%; with DHAP the response rate was 44.0% (95% CI for difference, −9.0% to 6.7%), meeting protocol-defined criteria for noninferiority of GDP (P = .005),” the investigators reported. “The transplantation rates were 52.1% with GDP and 49.3% with DHAP (P = .44). At a median follow-up of 53 months, no differences were detected in event-free survival (hazard ratio [HR] = 0.99; stratified log-rank P = .95) or overall survival (HR, 1.03; P = .78) between GDP and DHAP.”
Grade 3 or 4 adverse events during the first two cycles of chemotherapy occurred in 47% of patients receiving GDP vs 61% receiving DHAP (P < .001). Patients receiving GDP had fewer episodes of febrile neutropenia, reduced need for platelet transfusion support, less frequent hospitalizations related to toxicity, and less deterioration of quality of life from baseline. “Eight patients died as a result of protocol treatment–related complications: two during treatment with GDP and six after receiving DHAP,” the researchers noted. ■
Crump M, et al: J Clin Oncol. October 6, 2014 (early release online)