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Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in patients with advanced solid tumors metastatic to the liver

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Abstract

Background

Liver metastases in patients with cancer are associated with poor survival. We hypothesized that hepatic arterial infusion (HAI) of oxaliplatin combination therapy would have antitumor activity in these patients.

Patients and methods

Patients with advanced cancer and predominant liver metastases were treated on a phase I study of HAI oxaliplatin in combination with systemic bevacizumab, with or without HAI or systemic fluorouracil and/or leucovorin and/or cetuximab. Patients were divided into two treatment arms according to KRAS mutational status and physician choice. A “3 + 3” design was used.

Results

Among 76 patients (median age 61 years; 34 women; median number of prior therapies 4), the most common cancer was colorectal (CRC) (n = 58). Overall, the only dose-limiting toxicity was Grade 3 diarrhea (n = 2). The most common treatment-related toxicities were hypertension (n = 40), nausea (n = 29), fatigue (n = 28), and transaminitis (n = 26). Of 76 patients, one (1 %) had a complete response (CR), 12 (16 %) had a partial response (PR), and 12 (16 %) had SD for ≥6 months (total CR/PR/SD ≥6 months 25/76 = 33 %). In CRC (n = 58), total CR/PR/SD ≥6 months was 31 % (n = 18). Both patients with pancreatic neuroendocrine tumors achieved a PR (24+ months) and a CR (6+ months). Time to treatment failure (TTF) on the current regimen was 3.5 versus 2.8 months on patients’ prior systemic treatment (p = 0.37).

Conclusions

HAI oxaliplatin combination therapy with 5-fluorouracil, leucovorin, bevacizumab, and/or cetuximab was well tolerated and had antitumor activity in selected heavily pretreated patients with predominant liver disease.

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Acknowledgments

This work was supported in part by grant RR024148 from the National Center Research Resources, a component of the National Institutes of Health Roadmap for Medical Research, and by a Career Development Award from ASCO to A. M. Tsimberidou. Dr. Razelle Kurzrock received research/grant support from Hoffman-LaRoche and Genentech/Roche.

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Authors and Affiliations

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

    Apostolia M. Tsimberidou, Mark B. Leick, Joann Lim, Siqing Fu, Jennifer Wheler, Sarina A. Piha-Paul, David Hong, Gerald S. Falchook, Aung Naing, Ishwaria M. Subbiah, Adoneca Fortier & Razelle Kurzrock

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

    Rony Avritscher

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  1. Apostolia M. Tsimberidou
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Correspondence to Apostolia M. Tsimberidou.

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Tsimberidou, A.M., Leick, M.B., Lim, J. et al. Dose-finding study of hepatic arterial infusion of oxaliplatin-based treatment in patients with advanced solid tumors metastatic to the liver. Cancer Chemother Pharmacol 71, 389–397 (2013). https://doi.org/10.1007/s00280-012-2014-8

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