Phase I clinical trial of hepatic arterial infusion of cisplatin in combination with intravenous liposomal doxorubicin in patients with advanced cancer and dominant liver involvement. Cancer Chemother Pharmacol 2010 Nov;66(6):1087-93
Date
03/06/2010Pubmed ID
20204368Pubmed Central ID
PMC3410638DOI
10.1007/s00280-010-1266-4Scopus ID
2-s2.0-78149415403 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
PURPOSE: We conducted a phase I study of hepatic arterial infusion (HAI) cisplatin and systemic chemotherapy in patients with advanced cancer and dominant liver involvement.
METHODS: Patients were treated with HAI cisplatin 100-125 mg/m(2) (and 3,000 IU heparin) intraarterially and liposomal doxorubicin (doxil) 20-35 mg/m(2) IV (day 1) every 28 days. A "3 + 3" study design was used.
RESULTS: Thirty patients were treated (median age, 56 years). Diagnoses were breast cancer (n = 11), colorectal cancer (n = 8), ocular melanoma (n = 4), and other (n = 7). The median number of prior therapies was 5. The maximum tolerated dose (MTD) was at the 100/35 mg/m(2) level. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (n = 1) at the cisplatin 125 mg/m(2) and systemic doxil 35 mg/m(2) dose level. The most common toxicities were nausea/vomiting and fatigue. Of 24 patients evaluable for response, 4 (17%) had a partial response (PR) and 7 (29%) had stable disease (SD) for ≥4 months. Of the 11 patients with breast cancer, 3 (27%) had a PR and 5 (45%) had SD for ≥4 months. Of 4 patients with ocular melanoma, 1 had a PR and 1 SD for 4 months. One patient with hepatocellular carcinoma had SD for 4 months. Of 12 evaluable patients treated at the MTD, 2 (17%) had a PR and 5 (42%) had SD.
CONCLUSION: The MTD was HAI cisplatin 100 mg/m(2) and systemic doxil 35 mg/m(2). This regimen demonstrated antitumor activity, especially in breast cancer.
Author List
Tsimberidou AM, Moulder S, Fu S, Wen S, Naing A, Bedikian AY, Daring S, Uehara C, Ng C, Wallace M, Camacho L, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Carcinoma, Hepatocellular
Cisplatin
Disease-Free Survival
Doxorubicin
Drug Administration Schedule
Eye Neoplasms
Female
Hepatic Artery
Humans
Infusions, Intra-Arterial
Infusions, Intravenous
Kaplan-Meier Estimate
Liver Neoplasms
Male
Maximum Tolerated Dose
Melanoma
Middle Aged
Treatment Outcome
