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Enhanced efficacy of postoperative adjuvant chemotherapy in advanced gastric cancer: results from a phase 3 randomized trial (AMC0101)

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Abstract

Purpose

To improve the efficacy of adjuvant chemotherapy with mitomycin-C and fluoropyrimidine (Mf) in gastric cancer, we designed a new regimen (iceMFP) and investigated in a phase III study.

Methods

We randomly assigned 640 patients with resectable and macroscopically recognizable serosa-invading gastric cancer to Mf or iceMFP group during operation. The Mf consisted of intravenous mitomycin-C (20 mg/m2) at 3–6 weeks after surgery and oral doxifluridine (460–600 mg/m2/day) starting 4 weeks after the administration of mitomycin-C and continuing for 3 months. The iceMFP consisted of intraoperative intraperitoneal cisplatin (100 mg), intravenous mitomycin-C (15 mg/m2) on postoperative day 1, followed by oral doxifluridine for 12 months, and six monthly intravenous cisplatin (60 mg/m2). The primary endpoint was 3-year recurrence-free survival (RFS).

Results

A total of 521 patients (258 in Mf, 263 in iceMFP) were eligible for analysis after excluding patients with stage I disease, distant metastasis, or R1 resection. With a median follow-up of 3.5 years, the iceMFP group had a higher RFS (hazard ratio [HR] 0.70; 95 % confidence interval [CI] 0.54–0.90; p = 0.006; 3-year RFS 60 % vs. 50 %) and overall survival (HR 0.71; 95 % CI 0.53–0.95; p = 0.02; 3-year overall survival, 71 vs. 60 %) compared with the Mf group. This was confirmed at extension analysis after a median 6.6 years of follow-up. Both regimens were well tolerated with no differences in surgical complications.

Conclusion

The efficacy of adjuvant Mf was significantly improved by the additional therapeutic strategies of iceMFP. Considering negative results of AMC0201, these suggest that early initiation of chemotherapy and/or intraperitoneal cisplatin played a distinct role in the improved efficacy.

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Acknowledgments

The authors are indebted to Prof. J. Patrick Barron, Chairman of the Department of International Medical Communications of Tokyo Medical University, for his pro bono review of this manuscript.

Conflict of interest

Nobody reported potential conflict of interest relevant to this article.

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Authors and Affiliations

  1. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea

    Yoon-Koo Kang, Heung-Moon Chang, Min-Hee Ryu, Changhoon Yoo, Jae-Lyun Lee & Tae Won Kim

  2. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Jeong Hwan Yook & Byung Sik Kim

  3. Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Korea

    Dae Young Zang

  4. Department of Surgery, Hallym University Medical Center, Hallym University College of Medicine, Anyang, Korea

    Dae Hyun Yang

  5. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Se Jin Jang & Young Soo Park

  6. LSK Global Pharma Services, Seoul, Korea

    Young Jack Lee

  7. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

    Hwoon-Yong Jung & Jin-Ho Kim

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  1. Yoon-Koo Kang
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Correspondence to Yoon-Koo Kang.

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Kang, YK., Yook, J.H., Chang, HM. et al. Enhanced efficacy of postoperative adjuvant chemotherapy in advanced gastric cancer: results from a phase 3 randomized trial (AMC0101). Cancer Chemother Pharmacol 73, 139–149 (2014). https://doi.org/10.1007/s00280-013-2332-5

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