Advertisement

Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

      Purpose

      To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer.

      Patients and Methods

      Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m2 on day 1 and S1 at 40 mg/m2 twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m2 on days 1 and 21 and S1 30 mg/m2 twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate.

      Results

      A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery.

      Conclusions

      Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.
      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • van Hagen P.
        • Hulshof M.C.
        • van Lanschot J.J.
        • et al.
        Preoperative chemoradiotherapy for esophageal or junctional cancer.
        N Engl J Med. 2012; 366: 2074-2084
        • Sjoquist K.M.
        • Burmeister B.H.
        • Smithers B.M.
        • et al.
        Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis.
        Lancet Oncol. 2011; 12: 681-692
        • Malaisrie S.C.
        • Hofstetter W.L.
        • Correa A.M.
        • et al.
        The addition of induction chemotherapy to preoperative, concurrent chemoradiotherapy improves tumor response in patients with esophageal adenocarcinoma.
        Cancer. 2006; 107: 967-974
        • Jin J.
        • Liao Z.
        • Zhang Z.
        • et al.
        Induction chemotherapy improved outcomes of patients with resectable esophageal cancer who received chemoradiotherapy followed by surgery.
        Int J Radiat Oncol Biol Phys. 2004; 60: 427-436
        • Ajani J.A.
        • Xiao L.
        • Roth J.A.
        • et al.
        A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer.
        Ann Oncol. 2013; 24: 2844-2849
        • Alberts S.R.
        • Soori G.S.
        • Shi Q.
        • et al.
        Randomized phase II trial of extended versus standard neoadjuvant therapy for esophageal cancer, NCCTG (Alliance) trial N0849.
        J Clin Oncol. 2013; 31 (abstr 4026)
        • Cho S.H.
        • Shim H.J.
        • Lee S.R.
        • et al.
        Concurrent chemoradiotherapy with S-1 and cisplatin in advanced esophageal cancer.
        Dis Esophagus. 2008; 21: 697-703
        • Takayama Y.
        • Kochi M.
        • Fujii M.
        • et al.
        A case of complete response to S-1 plus CDDP in early-stage mucosal esophageal cancer.
        Anticancer Res. 2011; 31: 1019-1022
        • Mauer A.M.
        • Kraut E.H.
        • Krauss S.A.
        • et al.
        Phase II trial of oxaliplatin, leucovorin and fluorouracil in patients with advanced carcinoma of the esophagus.
        Ann Oncol. 2005; 16: 1320-1325
        • Conroy T.
        • Yataghene Y.
        • Etienne P.L.
        • et al.
        Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer.
        Br J Cancer. 2010; 103: 1349-1355
        • Zang D.Y.
        • Lee B.H.
        • Park H.C.
        • et al.
        Phase II study with oxaliplatin and S-1 for patients with metastatic colorectal cancer.
        Ann Oncol. 2009; 20: 892-896
        • van Meerten E.
        • van der Gaast A.
        • Tilanus H.W.
        • et al.
        Pathological analysis after neoadjuvant chemoradiotherapy for esophageal carcinoma: The Rotterdam experience.
        J Surg Oncol. 2009; 100: 32-37
        • Donahue J.M.
        • Nichols F.C.
        • Li Z.
        • et al.
        Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival.
        Ann Thorac Surg. 2009; 87 (discussion 398–399): 392-398
        • Courrech Staal E.F.
        • Aleman B.M.
        • Boot H.
        • et al.
        Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer.
        Br J Surg. 2010; 97: 1482-1496
        • Chang H.
        • Shin S.K.
        • Cho B.C.
        • et al.
        A prospective phase II trial of S-1 and cisplatin-based chemoradiotherapy for locoregionally advanced esophageal cancer.
        Cancer Chemother Pharmacol. 2014; 73: 665-671
        • Iwase H.
        • Shimada M.
        • Tsuzuki T.
        • et al.
        Concurrent chemoradiotherapy with a novel fluoropyrimidine, S-1, and cisplatin for locally advanced esophageal cancer: long-term results of a phase II trial.
        Oncology. 2013; 84: 342-349
        • Khushalani N.I.
        • Leichman C.G.
        • Proulx G.
        • et al.
        Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: Report of a clinical trial for patients with esophageal cancer.
        J Clin Oncol. 2002; 20: 2844-2850
        • Leichman L.P.
        • Goldman B.H.
        • Bohanes P.O.
        • et al.
        S0356: A phase II clinical and prospective molecular trial with oxaliplatin, fluorouracil, and external-beam radiation therapy before surgery for patients with esophageal adenocarcinoma.
        J Clin Oncol. 2011; 29: 4555-4560
        • O'Connor B.M.
        • Chadha M.K.
        • Pande A.
        • et al.
        Concurrent oxaliplatin, 5-fluorouracil, and radiotherapy in the treatment of locally advanced esophageal carcinoma.
        Cancer J. 2007; 13: 119-124
        • Conroy T.
        • Galais M.P.
        • Raoul J.L.
        • et al.
        Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): Final results of a randomised, phase 2/3 trial.
        Lancet Oncol. 2014; 15: 305-314
        • Herskovic A.
        • Russell W.
        • Liptay M.
        • et al.
        Esophageal carcinoma advances in treatment results for locally advanced disease: Review.
        Ann Oncol. 2012; 23: 1095-1103
        • Gebski V.
        • Burmeister B.
        • Smithers B.M.
        • et al.
        Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis.
        Lancet Oncol. 2007; 8: 226-234
        • Peiffert D.
        • Tournier-Rangeard L.
        • Gerard J.P.
        • et al.
        Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: Final analysis of the randomized UNICANCER ACCORD 03 trial.
        J Clin Oncol. 2012; 30: 1941-1948

      Comments

      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.