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

Abstract

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/m2 (and 3,000 IU heparin) intraarterially and liposomal doxorubicin (doxil) 20–35 mg/m2 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/m2 level. Dose-limiting toxicities were Grade 4 neutropenia (2 of 4 patients), and Grade 4 thrombocytopenia (n = 1) at the cisplatin 125 mg/m2 and systemic doxil 35 mg/m2 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/m2 and systemic doxil 35 mg/m2. This regimen demonstrated anti-tumor activity, especially in breast cancer.

A phase I study of hepatic arterial infusion of nab-paclitaxel in combination with intravenous gemcitabine and bevacizumab for patients with advanced cancers and predominant liver metastases

“…In that study, 3 (27%) patients had a PR and 5 (45%) had SD for ≥4 months and antitumor activity was particularly noted in patients with breast cancer and melanoma. [5]…”

“…This combination was well tolerated and was associated with rates of partial response [1] and stable disease (SD) ≥4 months of 11% and 32%, respectively [4]. We have also reported that HAI of cisplatin combined with IV liposomal doxorubicin was associated with a PR rate of 7% and an SD ≥4 months a rate of 45% [5]. In another phase I study of HAI paclitaxel in patients with advanced cancer and dominant liver involvement, results were disappointing.…”

Phase I clinical trial of hepatic arterial infusion of paclitaxel in patients with advanced cancer and dominant liver involvement

“…Also, docetaxel has been occasionally used in regional therapy, with some responses noted in squamous cell carcinoma of the lung [20], hypopharynx [21], head and neck, [22] and breast metastatic to the liver [8]. We previously reported that HAI oxaliplatin combination therapy has antitumor activity in patients with colorectal cancer and predominant liver metastases [23] and that HAI cisplatin and IV liposomal doxorubicin has antitumor activity in breast cancer with hepatic metastases [24]. …”

Hepatic Artery Infusion Chemotherapy for Liver Malignancy

“…In patients with breast cancer the median OS was 8.5 months, compared with 5.3 months for all other tumor types. 86 The use of this regimen seems to be safe and potentially has benefits in terms of RR, but more data are required before any judgment of a potential survival benefit can be made.…”

“…86 A total of 30 patients were included (11 breast cancer, 8 CRLM, 4 ocular melanoma, and 7 other: HCC/gastric/pancreatic/head and neck/neuroendocrine/cutaneous melanoma/leiomyosarcoma). The trial was designed to evaluate safety and toxicity but also reported on outcomes.…”