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A phase I/II trial of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine- and platinum-pretreated patients with advanced gastric cancer

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Abstract

Background

This is a phase I/II study of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine- and platinum-pretreated patients with metastatic or recurrent gastric cancer.

Methods

Phase I part with a standard 3 + 3 dose-escalation design was conducted to define the recommended phase II dose (RP2D) using four predefined dose levels of paclitaxel and irinotecan. The efficacy of RP2D was evaluated in a phase II part.

Results

In phase I part, 12 patients were enrolled. Dose-limiting toxicity was not observed. The RP2D was established as level 4 (paclitaxel—135 mg/m2 and irinotecan—160 mg/m2, every 3 weeks). In phase II part, 27 patients were enrolled. Thirty patients, including three patients at dose level 4 in the phase I part, were analyzed for efficacy. There was no complete response. Partial response and stable disease were reported in four and 16 patients, respectively (response rate 13.3 %, 95 % CI 0.0–25.5 %; disease control rate 66.6 %, 95 % CI 49.0–83.0 %). The median time to progression and overall survival was 3.0 months (95 % CI 1.8–4.2) and 10.1 months (95 % CI 6.6–13.6), respectively. Grade 3/4 toxicities included neutropenia (2 patients, 7.4 %), thrombocytopenia (1, 3.7 %), neutropenic fever (1, 3.7 %), and diarrhea (1, 3.7 %). There were no treatment-related deaths.

Conclusion

The RP2D of the paclitaxel and irinotecan combination is paclitaxel (135 mg/m2) and irinotecan (160 mg/m2), every 3 weeks. This combination as a second-line treatment for advanced gastric cancer shows tolerable toxicity and modest efficacy.

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Acknowledgments

Paclitaxel and irinotecan were kindly provided by Pfizer, Korea, and Jeil pharmaceutical Co Ltd, Korea, respectively. All authors have read and approved this manuscript and do not have any potential conflicts of interest, including specific financial interests and relationships and affiliations.

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

    Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim & Jong Seok Lee

  2. Department of Internal Medicine, Seoul Municipal Boramae Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

    In Sil Choi

  3. Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea

    Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Tae-You Kim, Yung-Jue Bang, Seock-Ah Im & Do-Youn Oh

  4. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

    Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Tae-You Kim, Yung-Jue Bang, Seock-Ah Im & Do-Youn Oh

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  1. Jin Won Kim
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Correspondence to Seock-Ah Im or Do-Youn Oh.

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Kim, J.W., Choi, I.S., Kim, Y.J. et al. A phase I/II trial of second-line chemotherapy with paclitaxel and irinotecan in fluoropyrimidine- and platinum-pretreated patients with advanced gastric cancer. Cancer Chemother Pharmacol 75, 1175–1182 (2015). https://doi.org/10.1007/s00280-015-2732-9

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