Biweekly Gemcitabine-Oxaliplatin and Dexamethasone for Relapsed/Refractory Malignant Lymphoma

Gemcitabine (GEM) and oxaliplatin (OX) are commonly used as weekly or biweekly therapy. In this regard, dose dense biweekly schedule seems of reasonable investigational value in GEM and OX combination for non-Hodgkin lymphoma (NHL). We conducted phase II study to evaluate the efficacy of the combination chemotherapy consisting of GEM, OX and dexamethasone (GemDOx) as a biweekly regimen in patients with relapsed or refractory NHL. Primary end point was objective response rate and secondary end points were toxicities, progression-free survival, overall survival, ASCC efficacy, rate for proceeding to ASCT. The inclusion criteria were relapsed or refractory malignant aggressive NHL of any histological subtypes: Patients who have refractory to first-line CHOP-like regimen; Patients who have first relapsed after first-line CHOP-like regimen or upfront autologous or allogeneic hematopoietic stem cell transplantation Chemotherapy was repeated every 4 weeks. Gemcitabine 1000 mg/m² in NS 500 mL was administered IV as a fixed dose rate infusion (FDRI, 10 mg/m²/min) on days 1 and 15. OX 85 mg/m²/d in 5DW 500 mL was administered IV over 6 hour on day 1 and 15. Dexamethasone 40 mg was admistered orally on day 1 through 4. All 29 patients were enrolled in this phase II study. Patients were male in 18 (62.1%), DLBCL in 16 (55.2%), stage III/IV in 25 (79.3%) and relapsed NHL in 23 (79.3) patients. Five (17.2%) patients had relapsed after upfront autologous/allogeneic stem cell transplantation. The most common prior chemotherapy was R-CHOP (n=16, 55.2%) and 17 (58.6%) were exposed to rituximab as prior chemotherapy. The median age and median prior chemotherapy were 53 (range 26–74) years old and 1 (range 1–4) cycle, respectively. IPI at relapse were 3/4 in 11 (37.9%). Only 17 (58.6%) and 9 (31.0%) patients could finish 2 or more and 4 or more cycles, respectively, and median received cycle was 2 (range 0.5–8). Four patients completed planned all 6 or more cycles, and 4 patients stopped GemDOx after 4 cycles for ASCT, and 1 patient lost initial response and progressed after 4 cycles. The reasons of drop-out were progressed disease in 15 (51.7%), lost to follow-up in 4 (13.8%), discrete of attending physician in 1 (3.4%) and withdraw of consent in 1 (3.4%). Maximal response rate was 27.9% (CR in 13.8%; PR in 13.8%) in intent-to-treat basis and 47.0% (CR in 23.5% and PR in 23.5%) among patients who had received at least 2 cycles of GemDOx. Stable disease was observed in 6 (20.7%) in intent-to-treat basis and 5 (29.4%) among patients who had received at least 2 cycles of GemDOx. Among patients who received 2 or more cycles, ORR was 53.4% (CR in 26.7% and PR in 26.7%) in relapsed NHL and 0% (SD in 50% and PD in 50%) in refractory NHL. Median survival and median progression-free survival were 20.526 (95% CI, 8.945–32.108) and 3.947 (95% CI, 0–10.358), respectively in all patients (Figure 1). Among patients who had completed 2 or more cycles, median survival and median progression-free survival were not reached and 10.625 (95% CI, 0–21.575), respectively. In conclusion, dose-dense biweekly GemDOx showed activity against highly unfavorable relapsed NHL, but failed to show superior overall response rate especially against refractory NHL. The main cause of failure was progressive disease although considering high drop-out rate.