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A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial

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Abstract

Purpose

Fluorouracil monotherapy, instead of the FOLFOX or FOLFIRI regimen, is administered to patients intolerant to oxaliplatin or irinotecan because of their adverse effects. A prospective clinical trial was designed to evaluate the efficacy and safety of fluorouracil monotherapy combined with panitumumab administered to patients with KRAS wild-type (WT) metastatic colorectal cancer (mCRC) intolerant to oxaliplatin and irinotecan. Screening for potential serum biomarkers to predict early therapeutic responses was conducted.

Methods

This single-arm, open-label multicenter phase II trial recruited patients with KRAS WT mCRC from 16 institutes between January 2012 and October 2014. Panitumumab (6 mg/kg) was intravenously administered every 2 weeks, combined with fluorouracil monotherapy, in 2-week cycles. The primary objective was overall response rate, and secondary endpoints included disease-control rate, progression-free survival, overall survival, toxicity, and blood-test data.

Results

Forty patients (male, 65.0%; median age, 74 years; colon cancer, 72.5%) met eligibility criteria and received 7 cycles (median) of fluorouracil chemotherapy combined with panitumumab. There were no treatment-related deaths. Median time to treatment failure was 3.2 months. 23 (57.5%) patients experienced at least one adverse effect ≥ grade 3. The response rate was 10.0% (95% confidence interval 2.8–23.7%). Median progression-free survival and overall survival were 4.3 and 11.3 months, respectively. Total lactase dehydrogenase (LDH) levels and those of LDH-4 and LDH-5, quickly changed with disease reduction or progression.

Conclusions

Fluorouracil monotherapy combined with panitumumab was safely administered to patients with KRAS WT mCRC intolerant to oxaliplatin and irinotecan. Serum LDH levels may predict early responses.

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Funding

This study was supported, in part, by the nonprofit organization Epidemiological and Clinical Research Information Network (ECRIN).

Author information

Author notes

  1. Yoshinori Munemoto and Mitsuro Kanda have contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Fukui Prefecture Saiseikai Hospital, Fukui, Japan

    Yoshinori Munemoto

  2. Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Mitsuro Kanda

  3. Department of Biostatistics, School of Public Health, Tokyo University Graduate School of Medicine, Tokyo, Japan

    Koji Oba

  4. Interfaculty Initiative in Information Studies, Tokyo University, Tokyo, Japan

    Koji Oba

  5. Department of Surgery, Rinku General Medical Center, Osaka, Japan

    Ho Min Kim

  6. Department of Surgery, Kinki Central Hospital, Itami, Japan

    Hiroyoshi Takemoto

  7. Division of Gastroenterology, Chiba Cancer Center, Chiba, Japan

    Tadamichi Denda

  8. Kitakyushu General Hospital, Kitakyushu, Japan

    Naoki Nagata

  9. Tokai Central Hospital, Kakamigahara, Japan

    Nao Takano & Junichi Sakamoto

  10. Department of Surgery, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Japan

    Mutsumi Fukunaga

  11. Department of Surgery, National Hospital Organization Nagoya Medical Center, Nagoya, Japan

    Masato Kataoka

  12. Department of Surgery, Kyoto Teishin Hospital, Kyoto, Japan

    Yukihiko Tokunaga

  13. Cancer Center, Aichi Medical University, Nagakute, Japan

    Hideyuki Mishima

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  1. Yoshinori Munemoto
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  2. Mitsuro Kanda
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  8. Nao Takano
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  13. Hideyuki Mishima
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Corresponding author

Correspondence to Mitsuro Kanda.

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Conflict of interest

Tadamichi Denda received research funding from Sanofi Co., Ltd., Boehringer Ingelheim Co., Ltd., and MSD Co., Ltd. Junichi Sakamoto serves as an advisor to Takeda Pharmaceutical Company Ltd. and received honoraria as lecture fees from Tsumura Co., Ltd., and from Chugai Pharmaceutical Co., Ltd. Hideyuki Mishima received lecture fees from Chugai Pharmaceutical Co., Ltd., and research funding from Chugai Pharmaceutical Co., Ltd. and Yakult Co., Ltd.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Fig. S1

Kaplan–Meier curves of (a) progression-free and (b) overall survival according to treatment regimen. (TIF 5194 KB)

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Munemoto, Y., Kanda, M., Oba, K. et al. A phase II trial to evaluate the efficacy of panitumumab combined with fluorouracil-based chemotherapy for metastatic colorectal cancer: the PF trial. Cancer Chemother Pharmacol 81, 829–838 (2018). https://doi.org/10.1007/s00280-018-3556-1

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