Phase II feasibility study of preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for esophageal squamous cell carcinoma

Abstract

The combination of docetaxel, cisplatin, and 5-fluorouracil (DCF) as preoperative treatment for esophageal squamous cell carcinoma (ESCC) has not been investigated. We carried out a multicenter phase II feasibility study of preoperative chemotherapy with DCF for ESCC. Patients with clinical stage II ⁄ III ESCC (International Union Against Cancer TNM classification system, 6th edition) were eligible. Chemotherapy consisted of i.v. docetaxel (70-75 mg ⁄ m 2 ) and cisplatin (70-75 mg ⁄ m 2 ) on day 1, and continuous infusion of fluorouracil (750 mg ⁄ m 2 ⁄ day) on days 1-5. Antibiotic prophylaxis on days 5-15 was mandatory. This regimen was repeated every 3 weeks with a maximum of three cycles allowed. After completion of chemotherapy, esophagectomy with extended lymphadenectomy was carried out. The primary endpoint was the completion rate of protocol treatment. Forty-two eligible patients were enrolled. During chemotherapy, the most common grade 3 or 4 toxicities were neutropenia (83%), anorexia (7%), and stomatitis (5%). Forty-one (98%) patients underwent surgery. The completion rate of protocol treatment was 90.5% (38 ⁄ 42). No treatment-related death was observed and the incidence of operative morbidity was tolerable. According to RECIST, the overall response rate after the completion of DCF was 64.3%. Pathological complete response was achieved in 17%. The estimated 2-year progression-free survival and overall survival were 74.5% and 88.0%, respectively. Although these data are preliminary, preoperative DCF was well tolerated. Antitumor activity was highly promising and warrants further investigation. This trial was registered with University Hospital Medical Information Network (no. UMIN000002396). (Cancer Sci 2013; 104: 1455-1460 T reatment of resectable esophageal cancer remains unsatisfactory. Among approaches, various multimodality combined therapies to improve local and distant relapse rates with preoperative chemotherapy or chemoradiotherapy have been investigated. Preoperative chemoradiotherapy was shown to increase disease-free and overall survival (OS) compared to the surgery-alone arm in some randomized trials, but was associated with a significantly increased rate of perioperative complications.(1,2) Furthermore, treatment strategies for specific histologic types are controversial, particularly with regard to adenocarcinoma and squamous cell carcinoma, given the general consensus that these two histological cancers should be considered as having different biologies.(3) Esophageal squamous cell carcinoma (ESCC) is a major histological type in Asia, including Japan, but most clinical trials have investigated treatment of resectable esophageal cancer without regard to type.One alternative approach to the adjuvant strategy is perioperative chemotherapy without radiation. In a Japan Clinical Oncology Study Group trial (JCOG 9907) which compared preoperative chemotherapy with postoperative chemotherapy in the treatment of stage II ⁄ III ESCC, preoperative chemotherapy with cisplatin and 5-fluorouracil (5...

Plasma ghrelin levels as a predictor of adverse renal events due to cisplatin-based chemotherapy in patients with esophageal cancer

“…Recently developed chemotherapy strategies have improved the outcomes of patients with ESCC (3)(4)(5). Although the DCF regimen results in favorable clinical responses in ESCC, cisplatin frequently induces AKI (2,5,6).…”

“…The recent development of systemic chemotherapy, including the combination of docetaxel, cisplatin and 5-fluorouracil (DCF), has improved long-term outcomes in patients with ESCC (3)(4)(5). Although the DCF regimen was expected to yield a high response rate in ESCC, the approach frequently results in severe adverse events such as acute kidney injury (AKI).…”

“…Elevated creatinine of any grade, as defined by the Common Terminology Criteria for Adverse Events (CTCAE), was previously observed in 11-21% (Grade 3 or 4 in 2%) of patients undergoing DCF therapy, and Grade 3 or 4 hyponatremia occurred in ∼30% (4,6,10,11). Patients undergoing DCF therapy generally receive hydration and diuresis to prevent AKI, but these approaches are not always successful.…”

Current Advancement in Multidisciplinary Treatment for Resectable cStage II/III Esophageal Squamous Cell Carcinoma in Japan

“…Recently, Hara et al reported a high response rate from triplet chemotherapy using CDDP, 5-FU, and docetaxel (DCF) and this could be another treatment option. 38) In the phase II trial, treatment completion rate was 90.5% and clinical response rate was 64.3% and pathological complete response was observed in 17%. For adverse events, neutropenia (≥ Grade 3) was observed in 83% of patients but there were no cases of treatment related deaths.…”

Current Status and Future Prospects for Esophageal Cancer Treatment

“…[52][53][54][55][56][57] Nomura et al 56) reported that the overall response rate was significantly higher in the DCF group than in the CF group in patients with clinical stage III or T3 esophageal SCC. After propensity score matching, the improvement in OS in the DCF group reached statistical significance (p = 0.05).…”