Palliative hepatic intraarterial chemotherapy (HIC) using a novel combination of gemcitabine and mitomycin C: results in hepatic metastases

Abstract

To evaluate repeated hepatic intraarterial chemotherapy (HIC) as a palliative treatment option for unresectable cholangiocarcinoma and liver metastases of various origins that were progressive under systemic chemotherapy. Between 2002 and 2006, 55 patients were treated in 4-week intervals (mean five sessions). Combined gemcitabine/mitomycin was administered intraarterially within 1 h. Tumor response was evaluated after the third session according to RECIST. Treated tumor entities were colorectal carcinoma (CRC) (n = 12), breast cancer (BC) (n = 12), cholangiocarcinoma (CCC) (n = 10), pancreatic (n = 4), ovarian (n = 3), gastric, cervical, papillary (each n = 2), prostate, esophageal carcinoma, leiomyosarcoma (each n = 1), cancer of unknown primacy (CUP) (n = 5). All patients tolerated the treatment well without any major side effects or complications. In total, there were 1 complete response (CR), 19 partial responses (PR), 19 stable (SD) and 16 progressive diseases (PD). We observed 5 PR, 3 SD and 4 PD in CRC; 1 CR, 4 PR, 6 SD in BC; and 2 PR, 2 SD and 6 PD in CCC. Median survival after first HIC was 9.7 months for CRC, 11.4 months for BC and 6.0 months for CCC. HIC with gemcitabine/mitomycin is a safe, minimally invasive, palliative treatment for hepatic metastases that are progressive under systemic chemotherapy. The treatment yields respectable tumor control rates in CRC and BC patients.

Apoptotic death mode of mitomycin C-treated HeLa cells and cellular localization of mitomycin C–induced P-glycoprotein

“…Breast cancers sensitive to neoadjuvant chemoendocrine therapies, including MMC, are associated with improved overall survival (Schwartz et al, 1995;Kelly et al, 2000;Liu et al, 2003). Recently, hepatic intra-arterial chemotherapy with gemcitabine/mitomycin was suggested to be a safe, minimally invasive, and palliative treatment for hepatic metastases in breast cancer and colorectal carcinoma patients (Vogl et al, 2008). MMC is also an inducer of sister chromatid exchanges, structural chromosome aberrations, micronuclei, and even apoptosis of some cultured cells (Bozsakyova et al, 2001).…”

Trans-arterial chemoperfusion for the treatment of liver metastases of breast cancer and colorectal cancer: Clinical results in palliative care patients

“…Most patients had a high number of lesions concerning the liver (29 of 36 patients had more than 5 lesions and therefore disseminated liver disease), they were all multiply pre-treated and therapy-resistant patients. Gemcitabine has not yet demonstrated high activity in CRC, but it has a more favourable toxicity profile compared to other cytostatic drugs and is well known in our institute as a treatment for palliative therapy[ 5 ].…”

“…For BC, gemcitabine is often administered, especially in second or third-line therapy[ 22 ]. In our institute, we have had good results using this combination[ 5 ].…”

“…Gemcitabine as an antimetabolite was chosen because of its tolerable hematologic toxicity and its effect in tumour biology similar to fluorouracil (5-FU). Mitomycin C was added to the chemotherapy protocol because in previous studies at our department it has demonstrated good response rates, especially in HIC pre-treated patients[ 5 ]. Primary endpoints of our retrospective analysis were tumour response, patient survival and the time at which the maximum therapeutic effect could be observed.…”

Hepatic Arterial Infusion of Gemcitabine plus Oxaliplatin as Second-Line Treatment for Locally Advanced Intrahepatic Cholangiocarcinoma: Preliminary Experience

“…Chemotherapy using hepatic arterial infusion (HAI) is a promising option for unresectable liver tumors of various origins [7,8,9]. Once exceeding 2-3 mm in size, hepatic cancerous tumors derive their blood supply from the hepatic artery, while normal hepatocytes are mainly perfused from the portal circulation [10].…”