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Outcomes of a Phase I/II Trial of Hepatic Arterial Infusion of Oxaliplatin Combined with Intravenous 5-Fluorouracil and l-Leucovorin in Patients with Unresectable Liver Metastases from Colorectal Cancer After Systemic Chemotherapy Failure

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Abstract

Purpose

The purpose of this study was to assess hepatic arterial infusion (HAI) of oxaliplatin combined with intravenous 5-fluorouracil (5-FU) and l-leucovorin (l-LV) in colorectal cancer (CRC) patients with systemic chemotherapy failure in a phase I/II trial.

Methods

CRC patients with unresectable liver metastases following standard systemic chemotherapy failure were eligible. A catheter-port system for HAI was placed using interventional radiology. In phase I, escalating doses of oxaliplatin for levels 1 and 2 were set at 50 and 100 mg/m2, respectively, and were combined with fixed doses of intravenous 5-FU (200 mg/m2 bolus and 2400 mg/m2/46-h continuous infusion) and l-LV (200 mg/m2). The dose-limiting toxicity (DLT) was assessed, and the recommended dose (RD) was estimated. In phase II, patients receiving RD were included to assess the 6-month survival rate (the expected rate 80%), overall survival time, tumor response, and toxicity.

Results

In phase I, none of the six enrolled patients exhibited DLT. RD for oxaliplatin by HAI was estimated as 100 mg/m2. In phase II, seven additional patients were enrolled. In patients receiving RD (n = 10), the disease control rates for total lesions and liver lesions were 30 and 70%, respectively. The 6-month survival rate and the overall survival time were 53.3% and 6.9 months, respectively. There were no adverse reactions equivalent to DLT in any of the patients.

Conclusions

The estimated RD for oxaliplatin by HAI in combination with intravenous 5-FU and l-LV was 100 mg/m2. This combination therapy was feasible and safe, but the expected efficacy was not achieved.

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Abbreviations

5-FU:

5-Fluorouracil

AE:

Adverse events

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CRC:

Colorectal cancer

CTA:

Computed tomography angiography

DLT:

Dose-limiting toxicity

DSA:

Digital subtraction angiography

HAI:

Hepatic arterial infusion

l-LV:

l-Leucovorin

PS:

Performance status

RD:

Recommended dose

RECIST:

Response Evaluation Criteria in Solid Tumors

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Authors and Affiliations

  1. Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Yozo Sato, Yoshitaka Inaba, Hidekazu Yamaura & Mina Kato

  2. Department of Medical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Takashi Ura, Daisuke Takahari & Kei Muro

  3. Department of Radiology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan

    Hideyuki Nishiofuku & Toshihiro Tanaka

Authors
  1. Yozo Sato
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  2. Yoshitaka Inaba
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  3. Takashi Ura
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  4. Hideyuki Nishiofuku
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  5. Hidekazu Yamaura
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  6. Mina Kato
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  7. Daisuke Takahari
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  8. Toshihiro Tanaka
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  9. Kei Muro
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Correspondence to Yozo Sato.

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The authors declare that they have no conflict of interest.

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Sato, Y., Inaba, Y., Ura, T. et al. Outcomes of a Phase I/II Trial of Hepatic Arterial Infusion of Oxaliplatin Combined with Intravenous 5-Fluorouracil and l-Leucovorin in Patients with Unresectable Liver Metastases from Colorectal Cancer After Systemic Chemotherapy Failure. J Gastrointest Canc 49, 132–137 (2018). https://doi.org/10.1007/s12029-016-9915-4

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