Preoperative docetaxel, cisplatin, and fluorouracil treatment with pegfilgrastim on day 7 for patients with esophageal cancer: A phase II study

Abstract

Aims The docetaxel and cisplatin plus 5‐fluorouracil (5‐FU) (DCF) regimen is expected to be superior to cisplatin plus 5‐FU for the preoperative treatment of esophageal cancer. However, a high risk of adverse effects, including febrile neutropenia (FN), has been reported. To evaluate the effectiveness and safety of DCF with prophylactic pegfilgrastim, we conducted a phase II study. Methods The regimen consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and a continuous infusion of 5‐FU (750 mg/m2 per day) on days 1–5. A single 3.6‐mg dose of pegfilgrastim was given as a subcutaneous injection on day 7 of each cycle. This regimen was repeated every 3 weeks for a maximum of three cycles. The primary endpoint was the grade‐2/3 histopathological response rate. Results Thirty‐seven eligible patients were enrolled and received DCF. Thirty‐four patients underwent esophagectomy. Two patients received chemoradiotherapy or radiotherapy without surgery. One patient withdrew consent and ended his hospital visit. One patient received additional radiotherapy before surgery. Histopathological responses of grade 3, grade 2, grade 1b, and grade 1a were observed in two (5.4%), 14 (37.8%), 10 (27.0%), and seven (18.9%) patients, respectively, and the primary endpoint was met. Of the 37 eligible patients, 11 (29.7%) developed FN in the first cycle. Conclusions Since the histopathological responses were as expected, DCF with prophylactic pegfilgrastim is considered to be effective as preoperative chemotherapy. However, the prophylactic use of pegfilgrastim on day 7 was insufficient to prevent FN.

Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer

“…'s study was 62 years (range: 44–75), and that of patients in this study was 66 years (41–73) 7 . Our patients were slightly older, but we do not know if this caused the difference in the FN rate 6 …”

“…Retrospective studies indicated that pegfilgrastim prophylaxis on day 7 reduced the risk of FN, but the incidence of FN varied (3–30%) (Table 5). 13–16 Our previous prospective study of DCF combined with pegfilgrastim on day 7 reported a 29.7% incidence of FN 6 . On the contrary, the results of a prospective study showed that DCF combined with pegfilgrastim on day 3 resulted in a low grade 4 neutropenia rate of 8.7% (95% confidence interval: 4.7–22.1) in two of 23 patients and an FN rate of 0% with prophylactic use of levofloxacin on days 5–9 (Table 5).…”

“…7 Our patients were slightly older, but we do not know if this caused the difference in the FN rate. 6 According to the definition of FN, in CTCAE v 5.0, FN is defined as an "absolute neutrophil count <1000/mm 3 with a single temperature of >38.3°C or a sustained temperature of ≥38°C for more than one hour". However, in the present study, we used the same FN criteria as those used in a report by Ishikawa et al, 7 that is, a neutrophil count less than 1000/μL and a temperature of 38°C or above.…”

“…5 Our previous report indicated that prophylactic pegfilgrastim administration on day 7, 24 h after 5-FU infusion, inadequately reduced FN risk, with a 29.7% incidence. 6 Conversely, Ishikawa et al reported that pegfilgrastim administered on day 3 effectively decreases FN risk. 7 Consequently, we conducted a feasibility study on DCF with prophylactic pegfilgrastim administered on day 3 as preoperative chemotherapy for esophageal cancer, using FN incidence as the primary endpoint to ascertain the reproducibility of previous findings.…”

“…To mitigate FN risk and ensure compliance with triplet regimens, pegfilgrastim, a long‐acting granulocyte colony‐stimulating factor (G‐CSF), should be given at least 24 h after completing myelosuppressive chemotherapy 5 . Our previous report indicated that prophylactic pegfilgrastim administration on day 7, 24 h after 5‐FU infusion, inadequately reduced FN risk, with a 29.7% incidence 6 . Conversely, Ishikawa et al.…”