Phase II Study of Irinotecan plus S-1 in Treatment of Advanced Gastric Cancer

Abstract

Objective: The efficacy and safety of irinotecan hydrochloride (CPT-11) plus oral fluoropyrimidine S-1 combination therapy in patients with previously untreated advanced gastric cancer was evaluated. Methods: The regimen comprised CPT-11 plus S-1: CPT-11, 60 mg/m2 (days 1, 15); S-1, 40 - 60 mg/body twice daily (days 1 - 21) followed by a 1-week rest, every 4 weeks. Primary endpoint was response rate. Secondary endpoints were tumor control rate, adverse events, relative dose intensity, and overall survival. Results: Twenty-five patients were enrolled; median age was 66 years. Response rate was 40% (95% confidence interval, 21.1% - 61.3%; complete response in 1; partial response in 9). Tumor control rate was 56.0%, median survival time was 436 days and relative dose intensities were 0.83 for CPT-11 and 0.85 for S-1. Incidence of grade 3 or greater neutropenia, anemia and diarrhea was 16%, 12%, and 12%, respectively.Conclusion: The present results indicate that CPT-11 plus S-1 offers lower treatment-related toxicity than regimens including cisplatin and is effective in patients with advanced gastric cancer.



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H. Bou, A. Tokunaga, H. Suzuki, N. Murata, Y. Sugiyama, N. Fukuda, M. Ishimaru and H. Suzuki, "Phase II Study of Irinotecan plus S-1 in Treatment of Advanced Gastric Cancer," Journal of Cancer Therapy, Vol. 4 No. 2, 2013, pp. 578-583. doi: 10.4236/jct.2013.42074.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] A. M. Murad, F. F. Santiago, A. Petroianu, et al., “Modified Therapy with 5-Fluorouracil, Doxorubicin, and Methotrexate in Advanced Gastric Cancer,” Cancer, Vol. 71, No. 1, 1993, pp. 37-41. doi:10.1002/1097-0142(19930701)72:1<37::AID-CNCR2820720109>3.0.CO;2-P
[2] B. Glimelius, K. Hoffman, U. Haglund, O. Nyren and P. O. Sjoden, “Initial or Delayed Chemotherapy with Best Supportive Care in Advanced Gastric Cancer,” Annals of Oncology, Vol. 5, No. 2, 1994, pp. 189-190.
[3] S. Pyrhonen, T. Kuitunen, P. Nyandoto and M. Kouri, “Randomized Comparison of Fluorouracil, Epidoxorubicin and Methotrexate (FEMTX) plus Supportive Care with Supportive Care Alone in Patients with Non-Resectable Gastric Cancer,” British Journal of Cancer, Vol. 71, No. 3, 1995, pp. 587-591. doi:10.1038/bjc.1995.114
[4] A. Ohtsu, Y. Shimada, K. Shirao, et al., “Randomized Phase 3 Trial of Fluorouracil Alone versus Fluorouracil plus Cisplatin versus Uracil and Tegafur plus Mitomycin in Patients with Unresectable, Advanced Gastric Cancer: The Japan Clinical Oncology Group Study (JCOG9205),” Journal of Clinical Oncology, Vol. 21, No. 1, 2003, pp. 54-59. doi:10.1200/JCO.2003.04.130
[5] Y. Kawano, M. Aonuma, Y. Hirota, H. Kuga, K. Sato, et al., “Intracellular Roles of SN-38, a Metabolite of the Camptothecin Derivative CPT-11, in the Antitumor Effect of CPT-11,” Cancer Research, Vol. 51, No. 16, 1991, pp. 4187-4191.
[6] Y. Sakata, I. Nakao, K. Futatsuki, et al., “An Early Phase II Trial of CPT-11 in Patients with Advanced Gastrointestinal Cancer,” Journal of Japan Society for Cancer Therapy, Vol. 27, No. 12, 1992, pp. 2028-2035.
[7] K. Futatsuki, A. Wakui, I. Nakao, et al., “Late Phase II Study of Irinotecan Hydrochloride (CPT-11) in Advanced Gastric Cancer. CPT-11 Gastrointestinal Cancer Study Group,” Japanese Journal of Cancer and Chemotherapy, Vol. 21, No. 7, 1994, pp. 1033-1038.
[8] K. Shirao, Y. Shimada, H. Kondo, et al., “Phase I-II Study of Irinotecan Hydrochloride Combined with Cisplatin in Patients with Advanced Gastric Cancer,” Journal of Clinical Oncology, Vol. 15, No. 3, 1997, pp. 921-927
[9] N. Boku, A. Ohtsu, Y. Shimada, et al., “Phase II Study of a Combination of Irinotecan and Cisplatin against Metastatic Gastric Cancer,” Journal of Clinical Oncology, Vol. 17, No. 1, 1999, pp. 319-323.
[10] M. Yoshida, N. Boku, A. Ohtsu, et al., “Combination Chemotherapy of Irinotecan plus Cisplatin for Advanced Gastric Cancer: Efficacy and Feasibility in Clinical Practice,” Gastric Cancer, Vol. 4, No. 3, 2001, pp. 144-149. doi:10.1007/PL00011737
[11] T. Yano and A. Ohtsu, “Evaluation of Newly Developed Agents for Gastric Cancer,” Japanese Journal of Cancer Clinics, Vol. 49, No. 7, 2003, pp. 583-588.
[12] T. Fukushima, H. Satake, J. Uchida, et al., “Preclinical Antitumor Efficacy of S-1: A New Oral Formulation of 5-Fluorouracil on Human Tumor Xenografts,” International Journal of Oncology, Vol. 13, No. 4, 1998, pp. 693-698.
[13] T. Shirasaka, K. Nakano, T. Takechi, et al., “Antitumor Activity of 1 M Tegafur-0.4 M 5-Chloro-2,4-Dihydroxypyridine-1 M Potassium Oxonate (S-1) against Human Colon Carcinoma Orthotopically Implanted into Nude Rats,” Cancer Research, Vol. 56, No. 11, 1996, pp. 2602-2606.
[14] K. Sugimachi, Y. Maehara, N. Horikoshi, et al., “An Early Phase II Study of Oral S-1, a Newly Developed 5-Fluorouracil Derivative for Advanced and Recurrent Gastrointestinal Cancers, the S-1 Gastrointestinal Cancer Study Group,” Oncology, Vol. 57, No. 3, 1999, pp. 202-210. doi:10.1159/ 000012032
[15] Y. Sakata, A. Ohtsu, N. Horikoshi, et al., “Late Phase 2 Study of Novel Oral Fluoropyrimidine Anticancer Drug S-1 in Advanced Gastric Cancer Patients,” European Journal of Cancer, Vol. 34, No. 11, 1998, pp. 1715-1720. doi:10.1016/S0959-8049(98)00211-1
[16] H. J. Lenz, C. G. Leichman, K. D. Danenberg, et al., “Thymidylate Synthase mRNA Level in Adenocarcinoma of the Stomach: A Predictor for Primary Tumor Response and Overall Survival,” Journal of Clinical Oncology, Vol. 14, No. 1, 1996, pp. 176-182.
[17] W. Ichikawa, T. Takahashi, K. Suto, et al., “Thymidylate Synthase Predictive Power Is Overcome by Irinotecan Combination Therapy with S-1 for Gastric Cancer,” British Journal of Cancer, Vol. 91, No. 7, 2004, pp. 1245-1250. doi:10.1038/sj.bjc.6602139
[18] H. Takiuchi, H. Nakahara, T. Tsujinaka, et al., “Phase I Study of S-1 Combined with Irinotecan (CPT-11) in Patients with Advanced Gastric Cancer (OGSG 0002),” Japanese Journal of Clinical Oncology, Vol. 35, No. 9, 2005, pp. 520-525. doi:10.1093/jjco/hyi148
[19] K. Fujitani, H. Takiuchi, H. Marahara, et al., “A Phase I/II Study of CPT-11 Plus S-1 in Patients with Advanced Gastric Cancer,” Japanese Journal of Cancer Clinics, Vol. 49, No. 7, 2003, pp. 605-609.
[20] Y. Komatsu, H. Takeda. M. Takei, et al., “A Phase I and PK Study of S-1 and Irinotecan (CPT-11) in Patients with Advanced Gastric Cancer (AGC),” Proceedings of the 38th American Society of Clinical Oncology, Orlando, 18-21 May 2002, p. 171.
[21] Y. Yamada, H. Yasui, A. Goto, et al., “Phase I Study of Irinotecan and S-1 Combination Therapy in Patients with Metastatic Gastric Cancer,” International Journal of Clinical Oncology, Vol. 8, No. 6, 2003, pp. 374-380. doi:10.1007/s10147-003-0359-z
[22] Japanese Research Society for Gastric Cancer, “Japanese Classification of Gastric Carcinoma,” Kanehara & Co., Ltd., Tokyo, 1995.
[23] N. Boku, S. Yamamoto, H. Fukuda, et al., “Fluorouracil versus Combination of Irinotecan plus Cisplatin versus S-1 in Metastatic Gastric Cancer: A Randomised Phase 3 Study,” The Lancet Oncology, Vol. 10, No. 11, 2009, pp. 1063-1069. doi:10.1016/S1470-2045(09)70259-1
[24] W. Koizumi, H. Narahara, T. Hara, et al., “S-1 plus Cisplatin versus S-1 Alone for First-Line Treatment of Advanced Gastric Cancer (SPIRITS Trial): A Phase III Trial,” The Lancet Oncology, Vol. 9, No. 3, 2008, pp. 215-221. doi:10.1016/S1470-2045(08)70035-4
[25] H. Narahara, H. Iishi, H. Imamura, et al., “Randomized Phase III Study Comparing the Efficacy and Safety of Irinotecan plus S-1 with S-1 Alone as First-Line Treatment for Advanced Gastric Cancer (Study GC0301/TOP-002),” Gastric Cancer, Vol. 14, No. 1, 2011, pp. 72-80. doi:10.1007/s10120-011-0009-5
[26] N. Uedo, H. Narahara, R. Ishihara, et al., “Phase II Study of a Combination of Irinotecan and S-1 in Patients with Advanced Gastric Cancer (OGSG0002),” Oncology, Vol. 73, No. 1-2, 2007, pp. 65-71. doi:10.1159/000120630
[27] T. Katsube, K. Ogawa, W. Ichikawa, et al., “Phase I/II Study of Irinotecan (CPT-11) and S-1 in the Treatment of Advanced Gastric Cancer,” Anticancer Drugs, Vol. 18, No. 5, 2007, pp. 605-610. doi:10.1097/CAD.0b013e3280262460

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