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Hepatic Intra-Arterial Paclitaxel for Breast Cancer Metastases
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: In a pilot study, ten women with liver predominant metastatic breast cancer were treated with intra-hepatic arterial infusion of paclitaxel (200 mg/m2 over 24 hours, monthly). The treatment proved well tolerated and somewhat effective. Three patients attained criteria for partial response and four others exhibited stable disease which lasted for several months. Prior systemic taxane therapy did not preclude response when administered by this route.
Source: Camacho LH, et al. Pilot study of regional, hepatic intra-arterial paclitaxel in patients with breast carcinoma metastatic to the liver. Cancer. 2007;109:2190-2196.
The liver as a site of dominant metastatic disease for patients with breast cancer is a well-recognized indicator of poor prognosis. In fact, approximately 25% of women with breast cancer will develop hepatic metastasis during the course of their illness.1 Camacho and colleagues at the M.D. Andersen Cancer Center in Houston performed a pilot study to test the feasibility and effectiveness of intrahepatic arterial infusion of paclitaxel in this setting. Ten women with chemotherapy-refractory breast carcinoma and predominant liver involvement were enrolled in the study. These patients were of good functional status (ECOG Performance Status 0 or 1) and did not have biochemical evidence of liver failure. Total bilirubin was less than 1 mg/dL and the prothrombin time and activated partial thromboplastin time were within in the normal limits. Furthermore, serum creatinine was less than 1.5 mg/dL. The patients underwent angiographic placement of a hepatic artery infusion catheter. Prior to drug infusion, a nuclear medicine flow study using Technetium-99 macroaggregated albumin particles was performed to demonstrate the flow distribution within the liver and to rule out the possibility of extrahepatic flow that might have resulted in gastrointestinal complications. Upon completion of the flow study, paclitaxel (200 mg/m2) was administered by 24-hour continuous infusion through the catheter. The regimen was repeated every four weeks until tumor progression, toxicity, or withdrawal of consent. All patients had been heavily pretreated and several had previous experience with taxanes.
Three of the 10 patients attained partial response that lasted for 6 months, 7 months, and 48 months; and four other patients had stable disease for five months to nine months. One patient underwent liver resection after receiving the hepatic arterial infusion and remained disease-free at 48 months. Eight of the 10 patients had received prior systemic taxane therapy either alone or with other cytotoxic drugs. However, no association between previous taxane exposure and the efficacy of the current regimen was established. In fact, all three patients who experienced partial response had had prior treatment with a taxane.
The most common treatment related toxicities were leukopenia, fatigue, nausea, and vomiting. With the exception of one patient who experienced grade 4 leukopenia, the remaining courses were well tolerated and not dissimilar from paclitaxel administered intravenously.
Thus, it appears that hepatic intra-arterial infusion with paclitaxel for women with liver-dominant metastatic breast cancer is feasible, well tolerated, and somewhat effective. It is encouraging to note that responses were seen in patients considered refractory to taxane administered intravenously. Perhaps the higher tissue level achieved or the prolonged exposure of the drug were factors involved in overcoming resistance.
Previous studies of hepatic arterial infusion using combined drugs (cisplatin and vinblastine) showed significant response rate, but the treatment was compromised by excessive toxicity.2
In colon cancer metastatic to the liver, there has been a reemergence of enthusiasm for intrahepatic arterial infusion. For example, Kemeny and colleagues3 have recently updated an earlier trial demonstrating that many patients had prolonged survival after such an approach was administered in the colon cancer setting. At 10 years, the overall survival was 41% for those that had received intrahepatic arterial infusion compared to 27% that had been given the same medicine intravenously. Whether such will be observed for breast cancer remains to be determined, but this pilot trial would suggest that a larger scale randomized control trial is warranted.
1. Wyld L, et al. Br J Cancer. 2003;89:284-290.
2. Fraschini G, et al. Am J Clin Oncol. 1988;11:34-38.
3. Kemeny NE, Gonen M. N Engl J Med. 2005;352:734-735.