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A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement

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Abstract

Background

We investigated hepatic arterial infusion (HAI) oxaliplatin combined with capecitabine +/− bevacizumab in advanced cancer with predominant liver involvement.

Methods

Patients received HAI oxaliplatin (140 mg/m2) and escalating doses of capecitabine (500, 750, and 1000 mg/m2), with (Group 1) or without (Group 2) bevacizumab (10 mg/kg IV). A 3 + 3 dose design was used, followed by an expansion phase.

Results

From 9/2009 to 2/2014, 61 patients (34 men, 27 women) were enrolled (Group 1 = 44; Group 2 = 17). Patients were treated in Group 2 if they had contraindications to bevacizumab (n = 13) or if there was no opening in Group 1 (n = 4). The median age was 60 years (range, 20–88). The most common cancers were colorectal (22 patients), liver (12), pancreatic (7), breast (4), and biliary tract (4). The median number of prior therapies was 3 (range, 1–12); 32 (53%) patients had received oxaliplatin. The dose-limiting toxicity was Grade 3 diarrhea and occurred in 2 patients receiving 1000 mg/m2 capecitabine. The maximum tolerated dose was HAI oxaliplatin 140 mg/m2, capecitabine 750 mg/m2, and bevacizumab 10 mg/kg. The most common toxicities were nausea/vomiting, anemia, thrombocytopenia, neutropenia, and hypomagnesemia. The rates of partial response and stable disease ≥ 4 months were 22% and 39% (Group 1) and 9% and 0% (Group 2). The respective median time to treatment failure and overall survival were 3 and 6.9 months (Group 1) and 1.5 and 5.9 months (Group 2).

Conclusion

HAI oxaliplatin combined with capecitabine +/− bevacizumab was well-tolerated and was associated with favorable outcomes in selected patients.

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Acknowledgements

Dr. Fountzilas has received a scholarship from the Hellenic Society of Medical Oncology (10/2017-09/2018).

Funding

NIH/NCI, award number P30 CA016672.

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Authors and Affiliations

  1. Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Elena Fountzilas, Elangovan Krishnan, Filip Janku, Siqing Fu, Daniel D. Karp, Aung Naing, Vivek Subbiah, David S. Hong, Sarina A. Piha-Paul & Apostolia-Maria Tsimberidou

  2. Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    David J. Vining

Authors
  1. Elena Fountzilas
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  2. Elangovan Krishnan
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  3. Filip Janku
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  4. Siqing Fu
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  5. Daniel D. Karp
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  6. Aung Naing
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  7. Vivek Subbiah
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  11. Apostolia-Maria Tsimberidou
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Corresponding author

Correspondence to Apostolia-Maria Tsimberidou.

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Fountzilas, E., Krishnan, E., Janku, F. et al. A phase I clinical trial of hepatic arterial infusion of oxaliplatin and oral capecitabine, with or without intravenous bevacizumab, in patients with advanced cancer and predominant liver involvement. Cancer Chemother Pharmacol 82, 877–885 (2018). https://doi.org/10.1007/s00280-018-3680-y

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  • DOI: https://doi.org/10.1007/s00280-018-3680-y

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