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Phase I study of larotaxel administered as a 1-h intravenous infusion every 3 weeks to Japanese patients with advanced solid tumours

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Abstract

Larotaxel (XRP9881, RPR109881), a novel semi-synthetic taxoid that shares a mode of action with the taxanes docetaxel and paclitaxel, was active in preclinical studies against a broad spectrum of tumour cells and tumour models refractory/resistant to taxanes, and have demonstrated clinical activity in taxane pre-treated/resistant metastatic breast cancer (MBC) patients. The current phase I dose-escalation study sought to define in Japanese patients with advanced solid tumours the maximum tolerated dose (MTD) and recommended dose (RD) of larotaxel administered as a 1-h intravenous infusion every 3 weeks. Eighteen patients were treated in total with 11 of those (61%) having previously received a docetaxel- or paclitaxel-based regimen. The MTD was defined as 90 mg/m2 following the occurrence of dose-limiting toxicities (DLTs) in two of five patients treated at this dose level including grade 4 neutropenia lasting >7 days or febrile neutropenia. The RD for phase II was consequently 75 mg/m2 q3w, with no DLTs in the six patients treated. The principal toxicity and DLT was neutropenia, with or without neutropenic complications. Partial responses were reported for 2 of 18 (11%) treated patients and a further 8 achieved stable disease (44%). The clearance 19.1–31.9 L/h was similar to that observed in Caucasian subjects with value of 33.0 ± 10.7 L/h. In conclusion, larotaxel 75 mg/m2, administered as a 1-h infusion every 3 weeks, appeared to be clinically tolerable in this Japanese patient population and showed early indications of activity.

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Acknowledgments

We would like to thank the patients and their families and the medical staff at both clinical centres.

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Authors and Affiliations

  1. Thoracic Oncology Division, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Nobuyuki Yamamoto

  2. Gastrointestinal Oncology and Endoscopy Division, Shizuoka Cancer Center Hospital, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan

    Narikazu Boku

  3. Medical Oncology, Department of Medicine, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Hironobu Minami

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  1. Nobuyuki Yamamoto
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  2. Narikazu Boku
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  3. Hironobu Minami
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Correspondence to Nobuyuki Yamamoto.

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Yamamoto, N., Boku, N. & Minami, H. Phase I study of larotaxel administered as a 1-h intravenous infusion every 3 weeks to Japanese patients with advanced solid tumours. Cancer Chemother Pharmacol 65, 129–136 (2009). https://doi.org/10.1007/s00280-009-1014-9

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  • DOI: https://doi.org/10.1007/s00280-009-1014-9

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