Nichols C R, Fox E P, Roth B J, Williams S D, Loehrer P J, Einhorn L H
Department of Medicine, Indiana University School of Medicine, Indianapolis.
J Clin Oncol. 1994 Jun;12(6):1245-50. doi: 10.1200/JCO.1994.12.6.1245.
We sought to determine the incidence of neutropenic fever associated with the use of standard-dose combination chemotherapy for small-cell lung cancer (SCLC) and to use these data as a template to analyze the costs and benefits of the routine use of granulocyte colony-stimulating factor (G-CSF).
We retrospectively reviewed records of 137 consecutive, unselected patients with SCLC treated with combination chemotherapy from January 1987 to March 1992. Admission criteria for neutropenic fever were temperature > or = 38.5 degrees C and an absolute neutrophil count < or = 500/microL. Neutropenic fevers were managed with a 25% dose reduction of the myelosuppressive drugs in subsequent cycles. Charge estimates for hospitalization ($1,244 per day) and G-CSF use ($2,027 per course) were estimated by reviewing charges to patients at Indiana University hospitalized for neutropenic fever or treated with outpatient G-CSF. We imposed assumptions from the Neupogen (filgrastim; Amgen Inc, Thousand Oaks, CA) licensing trial regarding the effectiveness of G-CSF and the Indiana University charge estimates on three models of G-CSF use: (1) preemptive--with all courses of chemotherapy, (2) reactive--with all cycles of chemotherapy following a neutropenic fever, and (3) dose reduction only (no G-CSF)--to derive charge estimates for G-CSF use.
Records of 137 patients with SCLC were identified and reviewed. The incidence of neutropenic fever was 12% in the first cycle of chemotherapy, and 18% overall, compared with the placebo- and G-CSF-treated arms of the Neupogen licensing trial, in which the incidence of neutropenic fever was 77% and 40%, respectively. Other therapeutic outcomes, such as neutropenic septic deaths, response rates, and survival, were comparable. We derived the following charge estimates for the three models of G-CSF: (1) preemptive--total charges = $1,287,481; (2) reactive--total charges = $276,154; and (3) dose reduction only--total charges = $192,820.
The incidence of neutropenic fever with standard-dose chemotherapy for SCLC was 18%. Routine use of G-CSF in SCLC patients treated with standard-dose chemotherapy appears to be expensive and is not associated with an obvious therapeutic benefit or cost savings. We suggest that careful analysis of the incidence of infectious complications, rather than granulocyte nadir and duration, be performed, and that clinical guidelines for the use of these effective, but expensive, products be developed.
我们试图确定与小细胞肺癌(SCLC)标准剂量联合化疗相关的中性粒细胞减少性发热的发生率,并以此数据为模板分析常规使用粒细胞集落刺激因子(G-CSF)的成本和效益。
我们回顾性分析了1987年1月至1992年3月间连续收治的137例未经挑选的接受联合化疗的SCLC患者的记录。中性粒细胞减少性发热的入院标准为体温≥38.5℃且绝对中性粒细胞计数≤500/μL。中性粒细胞减少性发热在后续化疗周期中通过将骨髓抑制药物剂量减少25%来处理。通过查阅印第安纳大学因中性粒细胞减少性发热住院或接受门诊G-CSF治疗的患者费用,估算住院费用(每天1244美元)和G-CSF使用费用(每个疗程2027美元)。我们根据Neupogen(非格司亭;安进公司,加利福尼亚州千橡市)许可试验中关于G-CSF有效性的假设以及印第安纳大学的费用估算,对三种G-CSF使用模式进行分析:(1)预防性——所有化疗疗程均使用;(2)反应性——中性粒细胞减少性发热后的所有化疗周期使用;(3)仅减少剂量(不使用G-CSF)——以得出G-CSF使用的费用估算。
确定并回顾了137例SCLC患者的记录。化疗第一周期中性粒细胞减少性发热的发生率为12%,总体发生率为18%,而Neupogen许可试验中使用安慰剂和G-CSF治疗的组中,中性粒细胞减少性发热的发生率分别为77%和40%。其他治疗结果,如中性粒细胞减少性败血症死亡、缓解率和生存率,具有可比性。我们得出三种G-CSF使用模式的以下费用估算:(1)预防性——总费用 = 1287481美元;(2)反应性——总费用 = 276154美元;(3)仅减少剂量——总费用 = 192820美元。
SCLC标准剂量化疗时中性粒细胞减少性发热的发生率为18%。在接受标准剂量化疗的SCLC患者中常规使用G-CSF似乎费用高昂,且未带来明显的治疗益处或成本节约。我们建议仔细分析感染并发症的发生率,而非粒细胞最低点和持续时间,并制定关于使用这些有效但昂贵产品的临床指南。