A phase II study of chemoselection with docetaxel, cisplatin, and 5–fluorouracil as a strategy for organ preservation in patients with resectable esophageal cancer (CROC trial).

Abstract

4027 Background: In patients with resectable esophageal squamous cell carcinoma (SCC), the outcomes of chemoradiotherapy (CRT) for good responders after three courses of induction chemotherapy (IC) with docetaxel, cisplatin, and 5–fluorouracil (DCF chemotherapy) were unclear. Methods: Patients with clinical stage IB–III (UICC 7th) resectable esophageal SCC were eligible. IC included docetaxel 75 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1, and 5–fluorouracil 750 mg/m2 on days 1–5, repeated every 3 weeks for 3 cycles. The response was evaluated after 2 and 3 courses of IC. Patients were considered to have a “remarkable response (RR)” if an endoscopic examination with a central review showed shrinking of the primary lesion equivalent to T1 and the short axis of the metastatic lymph nodes were all < 1 cm on computed tomography—in other words, down staging to T1N0M0 stage IA. Patients were considered to have a “poor response (POR)” if they had progressive disease or no signs of reduction. Patients who did not achieve RR or POR were deemed to have “limited partial response (LPR)”. CRT was administered to patients who achieved RR, and surgery was performed in patients who achieved LPR or POR. CRT included cisplatin 75 mg/m2 on day 1 and 5–fluorouracil 1000 mg/m2 on days 1–4, repeated every 4 weeks for 2 cycles. Radiotherapy was administered as 50.4 Gy in 28 fractions. The primary endpoint was a 1–year progression free survival (PFS) for RR followed by CRT. Results: A total of 92 patients were enrolled. Two patients with non–SCC (n = 1) and distant metastasis (n = 1) were excluded. Therefore, 90 patients were included in the analysis group. Although 1 patient could not continue IC due to renal failure, the remaining 89 patients completed 3 courses of IC. The response after IC were RR in 58.4% (52/89), LPR in 41.6% (37/89), and POR in 0.0% (0/89). Three patients who achieved RR underwent surgery owing to renal dysfunction (n = 1), curative irradiation difficulty due to intestinal malrotation (n = 1), and CRT refusal (n = 1). Six patients who achieved LPR underwent CRT owing to surgery refusal (n = 3), unresectable tumors (n = 2), and respiratory dysfunction due to emphysema (n = 1). The complete response rate for RR followed by CRT was 89.8%. During the median follow–up period of 33 months (range: 1–85), the 1 and 3–years overall survival (OS) for the analysis group were 96.6% and 74.1%, respectively. The 1 and 3–years organ preservation survival for the analysis group were 56.8% and 45.3%, respectively. The 1 and 3–years OS for RR followed by CRT (n = 49) vs. LPR followed by surgery (n = 31) were 100% vs. 93.1% and 83.7% vs. 62.8%, respectively (p = 0.06). The 1 and 3–years PFS for RR followed by CRT were 89.8% and 70.0%, respectively. Conclusions: Three courses of DCF chemotherapy followed by CRT is an effective treatment for patients with resectable esophageal SCC who respond to the IC regimen. Clinical trial information: 8086.