TY - JOUR
T1 - Phase I clinical trial of hepatic arterial infusion of paclitaxel in patients with advanced cancer and dominant liver involvement
AU - Tsimberidou, Apostolia M.
AU - Letourneau, Katherine
AU - Fu, Siqing
AU - Hong, David
AU - Naing, Aung
AU - Wheler, Jennifer
AU - Uehara, Cynthia
AU - McRae, Stephen E.
AU - Wen, Sijin
AU - Kurzrock, Razelle
N1 - Funding Information:
Acknowledgments Supported in part by Grant Number RR024148 from the National Center for Research Resources, a component of the NIH Roadmap for Medical Research (http://nihroadmap.nih.gov/ clinicalresearch/overview). We thank Joann Aaron for editing this manuscript.
PY - 2011/7
Y1 - 2011/7
N2 - Purpose: The survival of patients with liver metastases from solid tumors is poor. We conducted a phase I study of hepatic arterial infusion (HAI) paclitaxel in patients with advanced cancer and predominant liver involvement. Methods: Patients were treated with HAI paclitaxel 150-275 mg/m2 (and 15,000 IU heparin intraarterially) every 28 days. A "3 + 3" study design was used. Results: Twenty-six patients were treated (median age, 59 years). Diagnoses were colorectal cancer (n = 10), breast cancer (n = 7), and other (n = 9). The median number of prior therapies was four (range, 0-10). The maximum tolerated dose (MTD) was HAI paclitaxel 225 mg/m2. Dose-limiting toxicities (DLTs) included Grade 3 neuropathy (1 of 5 patients) at HAI paclitaxel 275 mg/m2 and Grade 4 thrombocytopenia and neutropenia, and Grade 3 mucositis (1 of 4 patients) at 250 mg/m2. None of the eight patients treated with HAI paclitaxel 225 mg/m2 experienced a DLT. The most common toxicities were nausea and peripheral neuropathy. Of 22 patients evaluable for response, 3 (13.6%) patients had SD for ≥4 months (colorectal cancer, n = 1; thyroid cancer, n = 1; and hepatocellular carcinoma, n = 1; duration of response was 4 months, 7.1 months, and 22.2+ months, respectively). Conclusion: The MTD of HAI paclitaxel was 225 mg/m2. This regimen was well tolerated and had antitumor activity in selected patients.
AB - Purpose: The survival of patients with liver metastases from solid tumors is poor. We conducted a phase I study of hepatic arterial infusion (HAI) paclitaxel in patients with advanced cancer and predominant liver involvement. Methods: Patients were treated with HAI paclitaxel 150-275 mg/m2 (and 15,000 IU heparin intraarterially) every 28 days. A "3 + 3" study design was used. Results: Twenty-six patients were treated (median age, 59 years). Diagnoses were colorectal cancer (n = 10), breast cancer (n = 7), and other (n = 9). The median number of prior therapies was four (range, 0-10). The maximum tolerated dose (MTD) was HAI paclitaxel 225 mg/m2. Dose-limiting toxicities (DLTs) included Grade 3 neuropathy (1 of 5 patients) at HAI paclitaxel 275 mg/m2 and Grade 4 thrombocytopenia and neutropenia, and Grade 3 mucositis (1 of 4 patients) at 250 mg/m2. None of the eight patients treated with HAI paclitaxel 225 mg/m2 experienced a DLT. The most common toxicities were nausea and peripheral neuropathy. Of 22 patients evaluable for response, 3 (13.6%) patients had SD for ≥4 months (colorectal cancer, n = 1; thyroid cancer, n = 1; and hepatocellular carcinoma, n = 1; duration of response was 4 months, 7.1 months, and 22.2+ months, respectively). Conclusion: The MTD of HAI paclitaxel was 225 mg/m2. This regimen was well tolerated and had antitumor activity in selected patients.
KW - Hepatic arterial infusion
KW - Paclitaxel
KW - Phase I trial
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U2 - 10.1007/s00280-010-1482-y
DO - 10.1007/s00280-010-1482-y
M3 - Article
C2 - 20941597
AN - SCOPUS:79959574175
SN - 0344-5704
VL - 68
SP - 247
EP - 253
JO - Cancer chemotherapy and pharmacology
JF - Cancer chemotherapy and pharmacology
IS - 1
ER -