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Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients with previously untreated advanced gastric cancer

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Abstract

Purpose

The primary objective of this Phase I study was to assess the safety and tolerability of the vascular endothelial growth factor signalling inhibitor cediranib in combination with cisplatin plus an oral fluoropyrimidine, in Japanese patients with previously untreated advanced gastric cancer.

Methods

Patients received continuous, once-daily oral doses of cediranib 20 mg in combination with either cisplatin (60 mg/m2 iv day 1) plus S-1 (40–60 mg bid, days 1–21) every 5 weeks for a maximum of eight cycles [Arm A]; or cisplatin (80 mg/m2 iv, day 1) plus capecitabine (1,000 mg/m2 bid, days 1–14) every 3 weeks for a maximum of six cycles [Arm B]. In both arms, the assessment period for dose-limiting toxicities (DLTs) was the first 21 days of cycle 1.

Results

Fourteen patients (Arm A, n = 6; Arm B, n = 8) were enrolled and received at least one dose of cediranib. One patient in each arm experienced a DLT (Arm A; decreased appetite, grade 3; Arm B, decreased appetite, fatigue and hyponatraemia, all grade 3). Overall, the most common adverse events were decreased appetite, fatigue and nausea (all n = 13 [92.9%]). Preliminary efficacy evaluation showed one confirmed (Arm A) and three unconfirmed (Arm A, n = 1; Arm B, n = 2) partial responses that were ongoing at data cut-off.

Conclusions

Cediranib 20 mg/day in combination with cisplatin and S-1 or capecitabine was tolerable, with no new toxicities identified, and showed preliminary evidence of antitumour activity.

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Acknowledgments

Funding for this study was provided by AstraZeneca. We thank Paul Williams, PhD, from Mudskipper Bioscience, who provided medical writing assistance funded by AstraZeneca.

Conflict of interest

X.S. and K.H.B. are employees of AstraZeneca and own stock. T.S., Y.Y, K.M., H.H., Y.S., D.T., K.T., T.E.N. and N.B. declare no conflicts of interest.

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Author notes

  1. Taroh Satoh

    Present address: Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, 2-15 Yamadaoka Suita City, Osaka, 565-0871, Japan

Authors and Affiliations

  1. Kinki University School of Medicine, Osaka, Japan

    Taroh Satoh & Hidetoshi Hayashi

  2. National Cancer Centre Hospital, Tokyo, Japan

    Yasuhide Yamada & Yasuhiro Shimada

  3. Aichi Cancer Centre Hospital, Aichi, Japan

    Kei Muro & Daisuke Takahari

  4. Shizuoka Cancer Centre, Shizuoka, Japan

    Keisei Taku

  5. St. Marianna University School of Medicine, Kanagawa, Japan

    Takako Eguchi Nakajima & Narikazu Boku

  6. AstraZeneca KK, Osaka, Japan

    Xiaojin Shi

  7. AstraZeneca, Alderley Park, Macclesfield, UK

    Kathryn H. Brown

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Satoh, T., Yamada, Y., Muro, K. et al. Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients with previously untreated advanced gastric cancer. Cancer Chemother Pharmacol 69, 439–446 (2012). https://doi.org/10.1007/s00280-011-1723-8

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