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Cancer Chemotherapy and Pharmacology

, Volume 75, Issue 2, pp 309–318 | Cite as

A Phase I study of cabazitaxel in patients with advanced gastric cancer who have failed prior chemotherapy (GASTANA)

  • Yoon-Koo KangEmail author
  • Baek-Yeol Ryoo
  • Shinkyo Yoon
  • Lin Shen
  • Jooyun Lee
  • Chenlu Wei
  • Yu Zhou
  • Min-Hee Ryu
Original Article

Abstract

Purpose

This Phase I dose-escalation study (GASTANA) evaluated the safety, tolerability, pharmacokinetics and preliminary antitumor activity of cabazitaxel in Asian patients with advanced gastric adenocarcinoma failing two prior chemotherapy regimens.

Methods

Cabazitaxel safety/tolerability was determined using a standard 3 + 3 dose-escalation design based on dose-limiting toxicities (DLTs) in Cycle 1. Three dose levels (DL) were planned: 20, 25 and 15 mg/m2 (DL 1, DL 2 and DL −1).

Results

Fifteen patients were evaluable for DLTs. At DL 1, no DLTs occurred in three patients. At DL 2, four patients were enrolled (one patient discontinued), with only one DLT observed [Grade 4 febrile neutropenia (FN)]; however, all four patients experienced FN, hence three more patients were enrolled at DL 1 who experienced two DLTs (Grade 4 neutropenia >7 days). In response, DL −1 was opened, with no DLTs observed in six patients. In the total population (n = 16), frequent Grade 3/4 toxicities included neutropenia (63 %) and FN (38 %), best overall responses included one partial response (6.3 %; DL −1) and eight stable disease (50 %), and median progression-free survival was 83 days.

Conclusions

No unexpected safety findings were observed. Significant toxicities included neutropenia and FN, potentially due to patients being heavily pretreated and the accumulated toxicity of prior taxane therapy.

Keywords

Cabazitaxel Advanced gastric cancer Asia Chemotherapy 

Notes

Acknowledgments

This study was funded by Sanofi. The authors received editorial support from Paul Scutt of MediTech Media Ltd, funded by Sanofi. This study was funded by Sanofi.

Conflict of interest

Yoon-Koo Kang has a consultancy/advisory role with Sanofi, Roche, Daiho and Novartis and has received funding from Sanofi, Roche, Jeil, Novartis and Bayer. Lin Shen has received remuneration from Roche, Novartis and Amgen, funding from Celgene, Taiho, Heng Rui, Sanofi and Roche, and has a consultant/advisory role with Roche and Novartis. Yu Zhou, Jooyun Lee and Chenlu Wei are employees of Sanofi. Baek-Yeol Ryoo, Shinkyo Yoon and Min-Hee Ryu have no conflicts to disclose.

References

  1. 1.
    Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2013) GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase No. 11. International Agency for Research on Cancer, Lyon. http://globocan.iarc.fr
  2. 2.
    Shen L, Shan YS, Hu HM, Price TJ, Sirohi B, Yeh KH, Yang YH, Sano T, Yang HK, Zhang X, Park SR, Fujii M, Kang YK, Chen LT (2013) Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol 14:e535–e547PubMedCrossRefGoogle Scholar
  3. 3.
    Van Cutsem E, Dicato M, Geva R, Arber N, Bang Y, Benson A, Cervantes A, Diaz-Rubio E, Ducreux M, Glynne-Jones R, Grothey A, Haller D, Haustermans K, Kerr D, Nordlinger B, Marshall J, Minsky BD, Kang YK, Labianca R, Lordick F, Ohtsu A, Pavlidis N, Roth A, Rougier P, Schmoll HJ, Sobrero A, Tabernero J, Van de Velde C, Zalcberg J (2011) The diagnosis and management of gastric cancer: expert discussion and recommendations from the 12th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2010. Ann Oncol 22(Suppl 5):v1–v9PubMedCrossRefGoogle Scholar
  4. 4.
    Ford H, Marshall A, Wadsley J, Coxon FY, Mansoor W, Bridgewater JA, Madhusudan S, Falk S, Middleton GW, Swinson D, Chau I, Thompson J, Blazeby JM, Cunningham D, Kareclas P, Dunn JA (2012) Cougar-02: a randomized phase III study of docetaxel versus active symptom control in advanced esophagogastric adenocarcinoma. J Clin Oncol 30. abstract LBA4Google Scholar
  5. 5.
    Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH (2012) Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 30:1513–1518PubMedCrossRefGoogle Scholar
  6. 6.
    Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P (2011) Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer—a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer 47:2306–2314PubMedCrossRefGoogle Scholar
  7. 7.
    National Comprehensive Cancer Network: Gastric Cancer. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Gastric Cancer (Version 1.2014). http://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf
  8. 8.
    Vrignaud P, Sémiond D, Lejeune P, Bouchard H, Calvet L, Combeau C, Riou J-F, Commercon A, Lavelle F, Bissery M-C (2013) Preclinical antitumor activity of cabazitaxel, a semi-synthetic taxane active in taxane-resistant tumors. Clin Cancer Res 19:2973–2983PubMedCrossRefGoogle Scholar
  9. 9.
    de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO (2010) Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 376:1147–1154PubMedCrossRefGoogle Scholar
  10. 10.
    National Comprehensive Cancer Network: Prostate Cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Prostate Cancer (Version 2.2014). http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
  11. 11.
    Pean E, Demolis P, Moreau A, Hemmings RJ, O’Connor D, Brown D, Shepard T, Abadie E, Pignatti F (2012) The European Medicines Agency review of cabazitaxel (Jevtana(R)) for the treatment of hormone-refractory metastatic prostate cancer: summary of the scientific assessment of the committee for medicinal products for human use. Oncologist 17:543–549PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Sanofi (2011) JEVTANA® (cabazitaxel) injection, summary of product characteristics. EMA, London, UKGoogle Scholar
  13. 13.
    Sanofi U.S. LLC (2013) JEVTANA® (cabazitaxel) injection, prescribing information. FDA, USAGoogle Scholar
  14. 14.
    National Cancer Institute (2010) Common terminology criteria for adverse events (CTCAE) version 4.03. http://evs.nci.nih.gov/ftp1/CTCAE/About.html
  15. 15.
    Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2:228–247CrossRefGoogle Scholar
  16. 16.
    Mita AC, Denis LJ, Rowinsky EK, de Bono JS, Goetz AD, Ochoa L, Forouzesh B, Beeram M, Patnaik A, Molpus K, Semiond D, Besenval M, Tolcher AW (2009) Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane, administered as a 1-hour infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 15:723–730PubMedCrossRefGoogle Scholar
  17. 17.
    Dieras V, Lortholary A, Laurence V, Delva R, Girre V, Livartowski A, Assadourian S, Semiond D, Pierga JY (2013) Cabazitaxel in patients with advanced solid tumours: results of a phase I and pharmacokinetic study. Eur J Cancer 49:25–34PubMedCrossRefGoogle Scholar
  18. 18.
    Yano R, Konno A, Watanabe K, Tsukamoto H, Kayano Y, Ohnaka H, Goto N, Nakamura T, Masada M (2013) Pharmacoethnicity of docetaxel-induced severe neutropenia: integrated analysis of published phase II and III trials. Int J Clin Oncol 18:96–104PubMedCrossRefGoogle Scholar
  19. 19.
    Fumoleau P, Trigo JM, Isambert N, Semiond D, Gupta S, Campone M (2013) Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours. BMC Cancer 13:460PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Mukai H, Takahashi S, Nozawa M, Onozawa Y, Miyazaki J, Ohno K, Suzuki K (2014) Phase I dose-escalation and pharmacokinetic study (TED 11576) of cabazitaxel in Japanese patients with castration-resistant prostate cancer. Cancer Chemother Pharmacol 73:703–710PubMedCrossRefGoogle Scholar
  21. 21.
    Kang EJ, Im SA, Oh DY, Han SW, Kim JS, Choi IS, Kim JW, Kim YJ, Kim JH, Kim TY, Lee JS, Bang YJ, Lee KW (2013) Irinotecan combined with 5-fluorouracil and leucovorin third-line chemotherapy after failure of fluoropyrimidine, platinum, and taxane in gastric cancer: treatment outcomes and a prognostic model to predict survival. Gastric Cancer 16:581–589PubMedCrossRefGoogle Scholar
  22. 22.
    Kang YK, Muro K, Ryu MH, Yasui H, Nishina T, Ryoo BY, Kamiya Y, Akinaga S, Boku N (2014) A phase II trial of a selective c-Met inhibitor tivantinib (ARQ 197) monotherapy as a second- or third-line therapy in the patients with metastatic gastric cancer. Invest New Drugs 32:355–361PubMedCrossRefGoogle Scholar
  23. 23.
    Lee MJ, Hwang IG, Jang JS, Choi JH, Park BB, Chang MH, Kim ST, Park SH, Kang MH, Kang JH (2012) Outcomes of third-line docetaxel-based chemotherapy in advanced gastric cancer who failed previous oxaliplatin-based and irinotecan-based chemotherapies. Cancer Res Treat 44:235–241PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Yoon-Koo Kang
    • 1
    Email author
  • Baek-Yeol Ryoo
    • 1
  • Shinkyo Yoon
    • 1
  • Lin Shen
    • 2
  • Jooyun Lee
    • 3
  • Chenlu Wei
    • 4
  • Yu Zhou
    • 5
  • Min-Hee Ryu
    • 1
  1. 1.Department of Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Department of GI OncologyPeking University Cancer Hospital and InstituteBeijingChina
  3. 3.SanofiSeoulKorea
  4. 4.SanofiBeijingChina
  5. 5.SanofiShanghaiChina

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