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

Abstract

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.

Dose-finding study of hepatic arterial infusion of irinotecan-based treatment in patients with advanced cancers metastatic to the liver

“…The treatment is arduous, requiring that patients remained in a supine position for 48 hours (recommended HAI irinotecan infusion period) to prevent catheter misplacement. As expected, the clinical outcomes of these HAI irinotecan regimens were poorer than those of HAI oxaliplatin regimens, as previously shown [19–23]. However, keeping in mind that some patients with CRC cannot tolerate oxaliplatin, HAI irinotecan combination therapy is a reasonable alternative in patients with CRC.…”

“…We have previously investigated the use of HAI oxaliplatin, cisplatin, or abraxane in combination regimens [19–23], which demonstrated antitumor activity in selected patients with advanced cancer and predominant liver metastasis. Irinotecan is a water-soluble derivative of camptothecin that exerts potent anti-cancer activity by inhibiting the nuclear enzyme topoisomerase I.…”

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 another phase I study of HAI paclitaxel in patients with advanced cancer and dominant liver involvement, results were disappointing. Treatment was well tolerated, but SD ≥ 4 months was noted only in 13.6% of patients [6]. …”

Transarterial chemoembolization (TACE) for colorectal liver metastases—current status and critical review

“…In this context, standardization of the interventional techniques as with DEB-TACE is mandatory, and targeted drugs should be included in the treatment regimes. Finally, based on the current data from the literature, studies should implement TACE earlier on in the treatment regimes as opposed to a pure salvage approach [30, 47, Tsimberidou et al 2011 [98] According to the guidelines, chemotherapeutic standards in the different lines for colorectal liver metastases include FOLFOX (1. folin acid (=leucovorin), 2. 5-fluoro-uracil, and 3. oxaliplatin), FOLFIRI In this context, it is worth to mention that cTACE was not associated with increased operating time, transfusion requirement, and peri-operative complication rates.…”