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A randomized trial of postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus neoadjuvant chemotherapy for clinical stage II/III squamous cell carcinoma of the thoracic esophagus (JCOG 9907)
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2008
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Surgical OncologyEsophageal CancerJcog 9907SurgeryMetronomic ChemotherapyOncologyGastrointestinal OncologyMetronomic TherapyPhase Iii TrialClinical TrialsRandomized TrialSurgical ComplicationsRadiation OncologyCancer ResearchHealth SciencesPostoperative Adjuvant ChemotherapyCancer TreatmentLung Cancer5- FluorouracilMedicineCancer Therapeutics
4510 Background: The phase III trial (JCOG9204) comparing postoperative adjuvant chemotherapy using cisplatin plus 5- fluorouracil (5-FU) with surgery alone showed superior disease-free survival in postoperative chemotherapy for patients (pts) with esophageal squamous cell carcinoma (ESCC) (Ando N, et al, J Clin Oncol 2003). This phase III trial was conducted to determine the optimal timing for giving chemotherapy. Methods: Pts with c-stage II, III (excluding T4) ESCC were randomized. In arm A, two courses of chemotherapy with cisplatin (80 mg/m2, div day1) plus 5-FU (800 mg/m2, ci day1–5) were given following surgery of transthoracic esophagectomy with lymphadenectomy. In arm B, two courses of chemotherapy same as arm A were given before surgery. Minimization method was used to balance nodal status (cN0/cN1) and institution. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), % complete resection, adverse events and surgical complications. Sample size was 330 pts to detect about 13% improvement in 5y-PFS with one-sided alpha 0.05 and power 0.80. Results: Between May 2000 and May 2006, 330 pts (A/B; 166/164, cN0/N1; 114/216) from 24 institutions were randomized. Median age was 61/61 years. No remarkable difference was seen in toxicity and complications between the arms. One treatment-related death was seen in each arm. The planned second interim analysis after completion of accrual was carried out in Mar 2007. Hazard ratio (HR) of PFS was 0.76 (favor in arm B, one-sided stratified logrank p = 0.044) which did not meet the prespecified stopping criteria (p < 0.0254; O’Brien & Fleming alpha spending function), however, arm B was highly superior in overall survival (OS) (HR 0.64, 95%CI: 0.45–0.91, two-sided p = 0.014). Data and Safety Monitoring Committee recommended the early publication. In updated analyses in Aug 2007, median PFS was 2.0 y in arm A, and 2.9 y in arm B, median OS was 2.9 y in arm A and was not reached in arm B. Conclusions: Preoperative chemotherapy with cisplatin plus 5-FU followed by surgery can be regarded as a new standard treatment for stage II/III ESCC. No significant financial relationships to disclose.