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Safety and pharmacokinetics of panitumumab in Japanese patients with advanced solid tumors

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Abstract

Background

Panitumumab is a fully human, monoclonal antibody against the epidermal growth factor receptor. Previous studies in non-Japanese patients with solid tumors showed that panitumumab exhibited nonlinear pharmacokinetics, was well tolerated (skin toxicities were the most common treatment-related adverse events), and had antitumor activity in some patients. This open-label, phase 1 study investigated panitumumab safety and pharmacokinetics in Japanese patients.

Methods

Japanese patients with advanced solid tumors were enrolled into one of three sequential panitumumab dose cohorts (cohort 1, 2.5 mg/kg weekly; cohort 2, 6.0 mg/kg every 2 weeks; and cohort 3, 9.0 mg/kg every 3 weeks) and received panitumumab until disease progression or drug intolerability. Safety endpoints included the incidence of adverse events, changes in laboratory values, and the appearance of anti-panitumumab antibodies. Serial pharmacokinetic samples were collected after the first and third doses of panitumumab. Tumors were assessed at week 8 and every 8 weeks thereafter.

Results

Eighteen patients (6 per cohort) were enrolled. No dose-limiting toxicities, investigator-reported infusion reactions, or deaths occurred. Seven patients had grade-3/4 adverse events; fatigue and anorexia were most common. The most common skin toxicities were rash and acneiform dermatitis. No neutralizing anti-panitumumab antibodies were detected. Panitumumab exhibited nonlinear pharmacokinetics, and antitumor activity was observed in 31% (4/13) of the patients with colorectal cancer.

Conclusion

In Japanese patients with solid tumors, panitumumab was well tolerated, demonstrated pharmacokinetic and safety profiles similar to those observed previously in non-Japanese patients, and exhibited encouraging antitumor activity in patients with colorectal cancer.

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Authors and Affiliations

  1. Gastrointestinal/Oncology Division, National Cancer Center Hospital East, 6-5-1 Kashiwanoha Kashiwa, Chiba, 277-8577, Japan

    Toshihiko Doi, Atsushi Ohtsu & Makoto Tahara

  2. National Cancer Center Hospital, Tokyo, Japan

    Tomohide Tamura & Yasuhide Yamada

  3. Oita University, Oita, Japan

    Kuniaki Shirao

  4. Takeda Bio Development Center Ltd., Tokyo, Japan

    Satoru Otani, Masayuki Ohkura & Tomoko Ohtsu

  5. Amgen Inc., Thousand Oaks, CA, USA

    Bing-Bing Yang

Authors
  1. Toshihiko Doi
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  2. Atsushi Ohtsu
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  3. Makoto Tahara
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  4. Tomohide Tamura
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  5. Kuniaki Shirao
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  6. Yasuhide Yamada
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  7. Satoru Otani
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  8. Bing-Bing Yang
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  9. Masayuki Ohkura
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  10. Tomoko Ohtsu
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Correspondence to Toshihiko Doi.

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Doi, T., Ohtsu, A., Tahara, M. et al. Safety and pharmacokinetics of panitumumab in Japanese patients with advanced solid tumors. Int J Clin Oncol 14, 307–314 (2009). https://doi.org/10.1007/s10147-008-0855-2

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  • DOI: https://doi.org/10.1007/s10147-008-0855-2

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