Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START)

Wasaburo Koizumi, Yeul Hong Kim, Masashi Fujii, Hoon Kyo Kim, Hiroshi Imamura, Kyung Hee Lee, Takuo Hara, Hyun Cheol Chung, Taroh Satoh, Jae Yong Cho, Hisashi Hosaka, Akihito Tsuji, Akinori Takagane, Mikito Inokuchi, Kazuaki Tanabe, Tatsuya Okuno, Mariko Ogura, Kazuhiro Yoshida, Masahiro Takeuchi, Toshifusa Nakajima, JACCRO and KCSG Study Group, M Fujii, H Baba, H Takiuchi, K Yoshida, T Kubota, W Koizumi, M Takeuchi, T Sasaki, Y Shimada, M Takeuchi, K Muro, T Ura, K Suzumura, M Odajima, S Saitoh, M Goto, K Moriichi, T Hoshi, K Chin, M Suenaga, Y Kuboki, K Miyachi, Y Kojima, O Hosokawa, H Fujii, Z Sase, S Asami, H Oshita, H Kato, F Sakashita, K Yamaguchi, H Hosaka, N Haga, R Aihara, A Takagane, H Kawasaki, J Itoh, T Takahata, N Hirabayashi, M Yamamoto, K Tanabe, M Nakamoto, Y Fujiwara, S Tachibana, T Nagaie, K Ohta, K Koeda, M Hyodo, Y Hosoya, T Sasaki, A Nakajo, T Kosaka, T Fujimura, M Uno, T Kamata, K Kobayashi, M Miyazaki, T Sato, W Okamoto, K Higuchi, S Tanabe, T Sasaki, W Koizumi, Y Fujishima, A Tsuji, T Hara, M Watanabe, A Keishiro, A Goto, O Yanagida, S Matsumoto, K Sumiyoshi, H Saeki, R Watanabe, S Yunoki, S Iijima, Y Sugimura, K Okita, Y Munakata, S Hidaka, H Andoh, J Akiyama, Y Takahashi, N Hatanaka, T Nakata, M Kataoka, H Ariyama, T Esaki, M Kochi, R Ohta, B Nakata, K Nishikawa, H Mizuno, M Izukura, T Mizushima, M Tanaka, T Shigematsu, T Egawa, T Kishimoto, T Nobuoka, N Hirahara, H Nemoto, K Yamazaki, Y Tajima, M Shibasaki, T Tsuda, A Hanai, K Sumiyoshi, M Kimura, K Hagiwara, K Iwasaki, H Musha, Y Kakudo, K Nabeshima, T Oiwa, H Ishikura, H Okitsu, M Inokuchi, S Ooka, S Hoshino, Y Iwasaki, T Iizuka, H Saito, S Tatebe, J Fujiita, A Higure, K Hirata, H Saito, K Suzuki, T Matsuda, M Hada, M Takahashi, S Y Kim, I S Woo, D Y Zang, J H Choi, M H Lee, H G Lee, S S Lee, Y H Kim, J S Kim, G W Lee, T Y Kim, H K Kim, J I Lee, K Y Shim, K H Lee, H C Jeung, S J Kim, Wasaburo Koizumi, Yeul Hong Kim, Masashi Fujii, Hoon Kyo Kim, Hiroshi Imamura, Kyung Hee Lee, Takuo Hara, Hyun Cheol Chung, Taroh Satoh, Jae Yong Cho, Hisashi Hosaka, Akihito Tsuji, Akinori Takagane, Mikito Inokuchi, Kazuaki Tanabe, Tatsuya Okuno, Mariko Ogura, Kazuhiro Yoshida, Masahiro Takeuchi, Toshifusa Nakajima, JACCRO and KCSG Study Group, M Fujii, H Baba, H Takiuchi, K Yoshida, T Kubota, W Koizumi, M Takeuchi, T Sasaki, Y Shimada, M Takeuchi, K Muro, T Ura, K Suzumura, M Odajima, S Saitoh, M Goto, K Moriichi, T Hoshi, K Chin, M Suenaga, Y Kuboki, K Miyachi, Y Kojima, O Hosokawa, H Fujii, Z Sase, S Asami, H Oshita, H Kato, F Sakashita, K Yamaguchi, H Hosaka, N Haga, R Aihara, A Takagane, H Kawasaki, J Itoh, T Takahata, N Hirabayashi, M Yamamoto, K Tanabe, M Nakamoto, Y Fujiwara, S Tachibana, T Nagaie, K Ohta, K Koeda, M Hyodo, Y Hosoya, T Sasaki, A Nakajo, T Kosaka, T Fujimura, M Uno, T Kamata, K Kobayashi, M Miyazaki, T Sato, W Okamoto, K Higuchi, S Tanabe, T Sasaki, W Koizumi, Y Fujishima, A Tsuji, T Hara, M Watanabe, A Keishiro, A Goto, O Yanagida, S Matsumoto, K Sumiyoshi, H Saeki, R Watanabe, S Yunoki, S Iijima, Y Sugimura, K Okita, Y Munakata, S Hidaka, H Andoh, J Akiyama, Y Takahashi, N Hatanaka, T Nakata, M Kataoka, H Ariyama, T Esaki, M Kochi, R Ohta, B Nakata, K Nishikawa, H Mizuno, M Izukura, T Mizushima, M Tanaka, T Shigematsu, T Egawa, T Kishimoto, T Nobuoka, N Hirahara, H Nemoto, K Yamazaki, Y Tajima, M Shibasaki, T Tsuda, A Hanai, K Sumiyoshi, M Kimura, K Hagiwara, K Iwasaki, H Musha, Y Kakudo, K Nabeshima, T Oiwa, H Ishikura, H Okitsu, M Inokuchi, S Ooka, S Hoshino, Y Iwasaki, T Iizuka, H Saito, S Tatebe, J Fujiita, A Higure, K Hirata, H Saito, K Suzuki, T Matsuda, M Hada, M Takahashi, S Y Kim, I S Woo, D Y Zang, J H Choi, M H Lee, H G Lee, S S Lee, Y H Kim, J S Kim, G W Lee, T Y Kim, H K Kim, J I Lee, K Y Shim, K H Lee, H C Jeung, S J Kim

Abstract

Purpose: Cisplatin plus 5-fluorouracil has been globally accepted as a standard regimen for the treatment for advanced gastric cancer. However, cisplatin has several disadvantages, including renal toxicity and the need for admission. S-1 plus cisplatin has become a standard treatment for advanced gastric cancer in East Asia. This phase III study was designed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer.

Methods: Patients were randomly assigned to receive docetaxel plus S-1 or S-1 alone. The docetaxel plus S-1 group received docetaxel on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The S-1 alone group received oral S-1 on days 1-28 of a 42-day cycle. The primary end point was overall survival.

Results: Of the 639 patients enrolled, 635 were eligible for analysis. The median overall survival was 12.5 months in the docetaxel plus S-1 group and 10.8 months in the S-1 alone group (p = 0.032). The median progression-free survival was 5.3 months in the docetaxel plus S-1 group and 4.2 months in the S-1 alone group (p = 0.001). As for adverse events, neutropenia was more frequent in the docetaxel plus S-1 group, but remained manageable.

Conclusion: As first-line treatment for advanced gastric cancer, docetaxel plus S-1 significantly improves median overall and progression-free survival as compared with S-1 alone. (ClinicalTrials.gov number: NCT00287768).

Figures

Fig. 1
Fig. 1
CONSORT diagram. OS overall survival, PFS progression-free survival, RR response rate
Fig. 2
Fig. 2
Kaplan–Meier estimate of overall survival and progression-free survival. a Overall survival. b Progression-free survival
Fig. 3
Fig. 3
Forest plot of the treatment effect on overall survival in subgroup analysis
Fig. 4
Fig. 4
Overall survival and progression-free survival in subgroup analysis. a Overall survival in the measurable population. b Overall survival in the non-measurable population. c Progression-free survival in the measurable population. d Progression-free survival in the non-measurable population

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