R-CHOP Every Two Weeks with Pegylated Filgastrim Support for the Treatment of CD20+ Aggressive Non Hodgkin's Lymphoma: Feasibility of Delivery On Time.

Several studies have shown that modifying CHOP (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 1.4 mg/m2, prednisone 100 mg) by adding rituximab (R) and/or shortening the time between cycles to 14 days improves survival in patients with aggressive non hodgkin's lymphoma (NHL). However, in some of the 14-day trials few patients withdrew from studies because of treatment delay more than 2 weeks. We implemented a two-stage phase II trial to assess the feasibility of delivering R-CHOP on time every two weeks with pegylated filgastrim (Neulasta) support for the treatment of CD20+ aggressive NHL.

Previously untreated patients with intermediate or high grade CD20+ NHL were assigned to receive R-CHOP every 2 weeks with pegylated filgastrim support. Lymphoblastic and mantle cell lymphoma were excluded. After 4 cycles, the patients who achieved complete response (CR) received 2 more cycles. Those who achieved a partial response (PR) were re-evaluated after receiving six cycles. If they were found in CR they got two more cycles (8 total). However, if they were found to be in PR they received radiotherapy or other therapy per treating physician. This interim report of this study reflects 16 patients enrolled so far between 8/4/05 till 8/8/09.

Fourteen patients received two or more cycles and are considered evaluable. Their mean age was 60 years (range: 47-77). Thirteen patients had Diffuse Large B cell Lymphoma (DLBL) and one patient had DLBL transformed from follicular lymphoma. Ten patients (71.4%) had an International Prognostic Index (IPI) low to low-intermediate and four (28.6%) had high intermediate to high IPI, two had a bulky disease and six had stage IV disease, three had stage III, the rest had stage I and II. Treatment delay was defined as more than two week delay in delivering the scheduled chemotherapy in two or more cycles due to absolute neutrophil count <500/microL or Platelets <75,000/microL. Nine patients received 6 cycles, two received 8, another two patients received 5 and one received 7 cycles (87 cycles total). Therapy was delivered on time without any delay in 8 patients (57% of patients). Only one patient (7.1%) met the defined criteria and had treatment delay >2 weeks for 2 cycles secondary to neutropenic fever (2.73% of 73 cycles, since the first cycle in each patient was not susceptible to delay). The study met the criteria (<=2 delays among the first 10 patient) for progression to the second stage. Five patients (6.84% of 73 cycles) had >1 week delay for non hematologic reasons (stroke, gastritis, ovarian cancer, perforated colon and drug allergy). Eleven patients had grade 3-4 neutropenia, five had grade 3anemia and one had grade 3thrombocytopenia. One patient had grade 2neuropathy. Median follow up time was 21.1 months. Overall response rate (CR+ PR) was 14/14 (100%), however one patient relapsed after 7 months and underwent stem cell transplantation.

It appears feasible and safe to deliver RCHOP every two weeks with pegylated filgastrim support in patients with CD20+ aggressive NHL. However in this group of 14 patients, there were some delays due to non hematologic toxicities and the delay due to hematologic toxicity was encountered in only one patient.

No relevant conflicts of interest to declare.