Achieving Full-Dose, On-Schedule Administration of ACE Chemotherapy Every 14 Days for the Treatment of Patients with Extensive Small-Cell Lung Cancer

Abstract

Extensive small-cell lung cancer (SCLC) is commonly treated with multiple cycles of chemotherapy. Reducing the time interval between cycles of chemotherapy (dose-dense chemotherapy) may improve outcomes in the treatment of extensive SCLC, as it has in other chemosensitive malignancies. To evaluate the feasibility of dose-dense chemotherapy in patients with extensive SCLC, this study evaluates a dose-dense doxorubicin/cyclophosphamide/etoposide (ACE) regimen, supported by the once-per-cycle administration of the hematopoietic growth factor pegfilgrastim. Patients received up to six 14-day cycles of ACE chemotherapy (doxorubicin 40 mg/m,(2) cyclophosphamide 1000 mg/m(2), etoposide 120 mg/m(2) on day 1 IV, plus oral etoposide 240 mg/m(2) daily on days 2-3). On day 4 of each cycle, patients received pegfilgrastim 6 mg by subcutaneous injection. Of 30 patients enrolled, 27 started chemotherapy and received pegfilgrastim. Full-dose, on-schedule chemotherapy was given to all 22 patients starting cycle 2, and in 107 (88%) of 121 cycles. Eighteen of the 27 patients (67%) received full-dose, on-schedule chemotherapy for all 6 cycles. The overall response rate was 17/27 (63%). Nine patients (33%) experienced hematologic toxicities that investigators considered severe or life-threatening. Four patients (15%) had febrile neutropenia. Full-dose, on-schedule dose-dense ACE chemotherapy is feasible with once-per-cycle pegfilgrastim support in extensive SCLC.

Risk factors for bone pain among patients with cancer receiving myelosuppressive chemotherapy and pegfilgrastim

“…Patient data from the remaining 22 studies that met the eligibility criteria were analyzed (Supplementary Table S1) [6][7][8][18][19][20][21][22][23][24][25][26][27][28][29][30][31].…”

Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now?

“…In patients with SCLC, full-dose, on-schedule, dose-dense ACE chemotherapy was found to be feasible with pegfilgrastim support [65]. …”

How Safe Is the Administration of Long-Acting Granulocyte Colony-Stimulating Factor in Cancer Patients?

“…In none of these trials was there evidence for a potential detrimental effect on neutropoiesis with the use of long-lasting G-CSF. Moreover, in the few trials in which the hematotoxic effects were shown for each separate chemotherapy cycle, no constellation was found in which neutropenia in cycle 2 was more pronounced than in the first cycle [34,40]. Thus, in all studies reported so far there is no evidence that the use of longacting G-CSF preparations in dose-dense settings leads to unexpected severe hematological toxicity.…”

“…Alternatively, it may be that the incidence of severe neutropenia was significantly higher in the study arm using longlasting G-CSF in 2-weekly chemotherapy protocols as compared to study arms using short-acting G-CSF in 2-weekly protocols or as compared to the study arms using pegfilgrastim in 3-weekly chemotherapy protocols. Although in most studies investigating dose-dense protocols these questions were not specifically addressed, these trials could demonstrate the safe and effective use of pegfilgrastim to support a variety of chemotherapy regimens with 14-day intervals for the treatment of early stage breast cancer [29][30][31][32][33][34][35][36][37][38][39], small cell lung cancer [40,41], non-small cell lung cancer [42], non-Hodgkin's lymphoma [43,44], Hodgkin's disease [45] and gastric cancer [46]. In none of these trials was there evidence for a potential detrimental effect on neutropoiesis with the use of long-lasting G-CSF.…”