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Pre-emptive oral clarithromycin reduces the skin toxicity of panitumumab treatment for metastatic colorectal cancer



Chemotherapy with panitumumab is expected to be well tolerated and improve survival in patients with metastatic colorectal cancer (mCRC). However, skin toxicities are its most common adverse events. The aim of this trial was to evaluate the efficacy and safety of pre-emptive antibiotic treatment with clarithromycin (CAM) to prevent panitumumab skin toxicities.


We conducted a phase lll, multicenter, open-label, randomized clinical trial on mCRC patients treated with panitumumab. Eligible patients were randomly assigned 1:1 to pre-emptive antibiotic and control groups. In the pre-emptive group, CAM administration (200 mg twice per day) continued daily through the panitumumab treatment period. The control regimen consisted of skin care only. The primary end point was the incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period.


Of 156 enrolled patients, 78 received pre-emptive antibiotic treatment, and 78 received reactive treatment. The number and incidence of grade ≥ 2 skin toxicities during the 6-week skin treatment period were 16 (21.3%) and 41 (54.7%) for the pre-emptive and control groups, respectively (HR, 0.32; 95% CI, 0.17–0.56). There was almost no difference in the rate of other adverse events between the two groups, but the incidence of grade ≥ 3 diarrhea in the pre-emptive group was high, at 8% vs. 1.3% in the control group. There were no treatment-related deaths.


Prophylactic oral CAM together with relatively simple skin care was found to be effective in suppressing the development of grade ≥ 2 skin toxicities induced by panitumumab.

Clinical trial registration


Date of registration

Sep 1st, 2013

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.


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The authors thank all the patients and their families. The authors also thank all the members of the Clinical Study Group of Osaka University (CSGO), Colorectal Group, Japan, for collection of data, and of the Supporting Center for Clinical Research and Education (SCCRE) in Osaka, Japan, for data management.

Author information





ST designed the study. KS, MU, and CM analyzed and interpreted the data. HO, YK, SM, SN, NH, and KM collected and assembled the data. TM contributed in drafting of the article. TK dedicated for critical revision of the article for important intellectual content. YD and HE finally approved the article.

Corresponding author

Correspondence to Ken Nakata.

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Ethics approval and consent to participate

The protocol was approved by the ethics committees at the participating sites. All patients signed informed consent before any study-related procedures were performed. The trial was carried out in accordance with the Declaration of Helsinki.

Conflict of interest

The authors declare no competing interests.

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Nakata, K., Komori, T., Saso, K. et al. Pre-emptive oral clarithromycin reduces the skin toxicity of panitumumab treatment for metastatic colorectal cancer. Int J Colorectal Dis 36, 2621–2627 (2021).

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  • Colorectal cancer
  • Panitumumab
  • Skin toxicity
  • Clarithromycin