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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. Cancer Chemother Pharmacol 2013 Feb;71(2):389-97

Date

11/13/2012

Pubmed ID

23143207

DOI

10.1007/s00280-012-2014-8

Scopus ID

2-s2.0-84874104755 (requires institutional sign-in at Scopus site)   13 Citations

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.

Author List

Tsimberidou AM, Leick MB, Lim J, Fu S, Wheler J, Piha-Paul SA, Hong D, Falchook GS, Naing A, Subbiah IM, Fortier A, Avritscher R, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Female
Hepatic Artery
Humans
Infusions, Intra-Arterial
Liver Neoplasms
Male
Middle Aged
Organoplatinum Compounds