Pegfilgrastim Supports Delivery of BEACOPP Chemotherapy Administered Every 14 Days. (2004)

Abstract The German Hodgkin’s Lymphoma Study Group has previously demonstrated that dose-escalated BEACOPP chemotherapy administered every 21 days with filgrastim significantly improved failure-free and overall survival compared to COPP-ABVD in patients with advanced Hodgkin’s Lymphoma (Diehl et al, Annals of Oncology 1998). An alternative approach to dose escalation is reduction of cycle length to 14 days. BEACOPP given every 14 days (BEACOPP-14) with filgrastim has been demonstrated to be feasible and effective with moderate acute toxicity (Sieber et al, JCO 2003). The aim of this study was to explore the feasibility of pegfilgrastim to support full delivery of BEACOPP-14 in high-risk Hodgkin’s lymphoma. All patients received BEACOPP-14 for up to 8 cycles. Patients were randomised to receive a single, 6mg, subcutaneous dose of pegfilgrastim on day 4 (d4) or 8 (d8) of each cycle. Primary endpoints were proportion of chemotherapy cycles given at planned dose and on time and proportion of patients receiving all administered cycles of chemotherapy at planned dose and on time. 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 &amp;gt;75% was administered for each myelosuppresive agent. Secondary endpoints included incidence of severe neutropenia (SN: absolute neutrophil count [ANC] &amp;lt;0.5 x 109/L) and response to chemotherapy. This exploratory study used descriptive statistics; therefore, no formal comparisons were made between groups. A total of 41 patients were randomised (d4: n=21, d8: n=20). In both groups 81% of chemotherapy cycles were given at planned dose and on time (d4: 122/151 cycles, d8: 116/143 cycles). Three of 29 cycles (d4) and 5/27 cycles (d8) had a delay and a reduction. Twenty-one of 29 cycles (d4) and 15/27 cycles (d8) were delayed only. Lack of haematological recovery (ANC &amp;lt;2x109/L and/or platelet count &amp;lt;80x109/L) led to delays in 9/21 (d4) and 2/15 (d8) cycles. Dose delays/reductions occurred more frequently in later chemotherapy cycles. Over 80% of patients in cycle 4, &amp;gt;70% patients in cycle 6, and &amp;gt;50% of patients in cycle 8 received chemotherapy at planned dose on time in both groups. Over all cycles administered, 33% d4 and 40% d8 patients received chemotherapy at planned dose and on time. Nine of 21 patients (43%) in the d4 group compared to 15/20 patients (75%) in the d8 group had at least one incidence of SN. Serious adverse events reported by more than one subject were pneumonia, fever, febrile neutropenia, anaemia and syncope, which were similar in incidence between groups. At least 85% of patients had a response to BEACOPP-14, the remaining patients (d4: 14%, d8: 15%) had no response recorded. This exploratory study suggests that full delivery of BEACOPP-14 with pegfilgrastim administered on d4 or d8 is feasible. The safety profile for the 2 groups was similar although the incidence of SN in the d4 group may indicate that administration of pegfilgrastim immediately after the end of myelosuppressive chemotherapy could offer enhanced protection against SN.