Clinical Efficacy and Cost Benefit of Low-Dose Granulocyte Colony-Stimulating Factor after Standard Chemotherapy in Patients with Non-Hodgkin’s Lymphoma.
Authors: Hashino Satoshi , Morioka Masanobu , Irie Tatsuro , Shiroshita Noriyuki , Kawamura Tsugumichi , Suzuki Sachiko , Iwasaki Hiroshi , Umehara Shintaro , Kakinoki Yasutaka , Kurosawa Mitsutoshi , Kahata Kaoru , Izumiyama Koh , Kobayashi Hajime , Onozawa Masahiro , Takahata Mutsumi , Fujisawa Fumie , Kondo Takeshi , Asaka Masahiro 
Published: April 2020

Abstract
High costs of molecule-targeted drugs such as rituximab, ibritumomab and tositumomab have given rise to an economical issue for treating patients with non-Hodgkin’s lymphoma (NHL). Granulocyte colony-stimulating factors (G-CSF), which are also expensive, are widely used for treating neutropenia after chemotherapy. In Japan, lenograstim at 2 μg/kg (almost 100 μg/body) or filgrastim at 50 μg/m2 (almost 75 μg/body) is commonly administered for patients with NHL after chemotherapy. Therefore, cost-effectiveness is an important issue in treatment for NHL. Patients with advanced-stage NHL who needed chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen with or without rituximab were enrolled in this randomized cross-over trial to investigate the efficacy and safety of low-dose G-CSF. Half of the patients were administered 75 μg filgrastim in the first course after neutropenia and 50 μg lenograstim in the second course, and the other half were crossed over. Forty-seven patients were enrolled in this cross-over trial, and twenty-four patients completed the trial. Frequencies of leukocytopenia and neutropenia of grade 4 were similar in patients who received filgrastim courses and those who received lenograstim courses (p=0.6366 in leukocytopenia and p=0.2207 in neutropenia, respectively). Durations of leukocytopenia and netropenia of grade 4 in each treatment course were not different statistically (p=0.3892 in leukocytopenia and p=0.1476 in neutropenia, respectively), and each period of G-CSF administration in both courses was not different statistically (p=0.0676). Frequency of fever higher than 37.5 degrees (p=0.6826) and duration of fever (p=0.7455) were also not statistically different in the two treatment courses. Documented infection containing FN after chemotherapy was not statistically different (p=0.1213). Although the administration dose of G-CSF was not determined on the basis of body weight or body surface area, eight febrile patients were not administered insufficient dose of G-CSF. Therefore, compared with the standard-dose G-CSF course (filgrastim at 75 μg), there was no statistically increased frequency of antibiotic usage in the low-dose G-CSF course (lenograstim at 50 μg) (p=0.2199). The total cost of G-CSF in the low-dose G-CSF (lenograstim at 50 μg) course was significantly lower than that in the standard-dose G-CSF (filgrastim at 75 μg) course (p&lt;0.0001). In this clinical study, the total cost of treatment with G-CSF at a lower dose was 62% of the cost of treatment at the standard dose. This study also suggests that the half dose descalation of lenograstim is as effective as the standard dose of filgrastim.