Pegfilgrastim Supports Delivery of CHOP-R Chemotherapy Administered Every 14 Days: A Randomised Phase II Study.

CHOP chemotherapy administered every 21 days has been the standard regimen for treatment of aggressive NHL for many years. Recent studies have shown improvements in both complete remission and survival following addition of Rituximab to CHOP 21 (Coffier et al, NEJM 2002) and following reduction of the cycle length of standard 21 day CHOP to 14 days (Pfreundschuh et al, Blood 2004). Previous studies with CHOP 14 have demonstrated the need for filgrastim to allow for administration of chemotherapy at planned dose and on time in this setting. The primary aim of this study was to explore the feasibility of 14 day CHOP chemotherapy plus Rituximab (CHOP-R 14) with pegfilgrastim and filgrastim. This was an open-label, randomised study of a single administration pegfilgrastim (6mg, day 2) or daily administration filgrastim (5 μg/kg; day 2 until ANC>10x10⁹/L) in subjects with aggressive B-cell NHL being treated with CHOP-R 14 for up to 6 cycles. The endpoints of the study were proportion of cycles given at planned dose on time, proportion of subjects receiving planned dose of chemotherapy on time, and clinical response. A cycle was considered “on time” if it started <17 days after the start of the previous cycle, and at “planned dose” if a dose of >75% was administered for each agent (excluding prednisone and vincristine). This was an exploratory study using descriptive statistics to summarise endpoints therefore no formal comparisons were made between the groups. Twenty-seven subjects were randomised to filgrastim and 33 to pegfilgrastim. Twenty-six (96%) filgrastim and 32 (97%) pegfilgrastim subjects received study drug; 22 (81%) filgrastim and 30 (91%) pegfilgrastim subjects received all 6 cycles of chemotherapy. The treatment groups were generally well balanced at baseline but in the pegfilgrastim group there were more subjects randomised and more subjects completed all 6 cycles. Of the cycles planned, 93% (145/156) in the filgrastim group and 98% (188/192) in the pegfilgrastim group were administered. Of the cycles administered, 94% (137/145) and 93% (175/188) respectively were at planned dose and on time. Across the whole study, the proportion of subjects receiving chemotherapy at planned dose and on time was 81% (21/26) filgrastim and 69% (22/32) pegfilgrastim; with the proportion of subjects decreasing from cycle 2–6 (92% filgrastim and 100% pegfilgrastim in cycle 2 vs. 91% and 83% in cycle 6). The proportion of subjects reporting severe or life threatening adverse events were comparable (9 subjects, 35% filgrastim, 13 subjects, 41% pegfilgrastim). The only events reported by more than 2 subjects in either treatment group were anaemia (4, 15% vs. 4, 13%), febrile neutropenia (1, 4% vs. 3, 9%), and pyrexia (0% vs. 3, 9%). By the end of treatment, the overall response rate was 96% (25/26) for filgrastim and 94% (30/32) for pegfilgrastim subjects. This exploratory study suggests that it is feasible to deliver CHOP-R chemotherapy at planned dose and on time every 14 days, with once per cycle administration of pegfilgrastim or daily administration of filgrastim. Pegfilgrastim is safe and well tolerated with a safety profile similar to daily filgrastim in this subject population.