Pharmacologic Studies of Hepatic Intra-Arterial Chemotherapy

Ensminger, William D.; Gyves, John W.

doi:10.1007/978-1-4613-2593-2_13

Cited by 69 publications

(89 citation statements)

References 15 publications

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“…These differences in MMC bioavailability are not due to the dose administered; on the contrary, the highest doses were given to patients with pelvic infusions (Table I). These differences in peripheral MMC delivery and thus in target accumulation can probably be explained by the higher blood flow rate in the liver (1.6 I min:') (6): this would be in agreement with the general principle according to which the local drug concentration in IA chemotherapy depends essentially on the flow rate in the artery used for infusion (7,8). Organ perfusions may thus be a limiting factor for target site exposure in IA MMC-mc treatment.…”

Section: Discussionsupporting

confidence: 55%

Systemic blood levels after intra-arterial administration of microencapsulated mitomycin C in cancer patients

Milano

Boublil

Bruneton

et al. 1985

European Journal of Drug Metabolism and Pharmacokinetics

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Systemic delivery of mitomycin C (MMC) was studied in 6 patients administered microencapsulated MMC (MMC-mc) by an intra-arterial route (IA): 3 IA liver infusions, 3 IA pelvic infusions. Pharmacokinetic data revealed a lower blood MMC availability (peak plasma levels, AUC 0-4 hours) for the pelvis than for the liver; this was attributed to differences in the blood flow infusion rates at these two sites of administration. Direct comparison of systemic MMC exposure was possible for one patient, who received both IA liver MMC (10 mg in standard form, which served as the control) and IA liver MMC-mc (20 mg the day after). The 65% reduction in MMC-mc bioavailability observed for this patient indicates a quantitative local improvement in exposure to the drug and correlates well with the low incidence of systemic side effects noted in preliminary clinical studies.

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Section: Discussionsupporting

confidence: 55%

Systemic blood levels after intra-arterial administration of microencapsulated mitomycin C in cancer patients

Milano

Boublil

Bruneton

et al. 1985

European Journal of Drug Metabolism and Pharmacokinetics

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“…Moreover, hepatic extraction of some chemotherapeutic agents, particularly the fluoropyrimidines, allows larger doses to be given with minimal systemic side effects. 16 Although surgical resection is currently the optimal curative therapy for HCC, 17 it is possible for only 14 -30% of patients at initial presentation. 18 Among the investigational modalities proposed for making unresectable HCC lesions resectable are radiolabeled antiferritin antibodies, 19 radiation plus chemotherapy, 20 and multimodality therapy involving hepatic artery ligation, radioimmunotherapy or radiotherapy, and HAI therapy.…”

Section: Discussionmentioning

confidence: 99%

Surgery After Downstaging of Unresectable Hepatic Tumors With Intra-Arterial Chemotherapy

et al. 2000

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“…FUDR has 95% hepatic extraction when continuously infused into the hepatic artery, resulting in a 16-fold higher concentration in hepatic metastases compared with venous administration. 78 Two meta-analyses of earlier trials were conducted to determine if there was a survival benefit associated with HAI FUDR used in a metastatic setting. A meta-analysis based on individual patient data from all randomized studies comparing HAI FUDR with intravenous fluoropyrimidines in patients with metastases confined to the liver showed that HAI FUDR dramatically enhanced tumor response rates (41% versus 14%, P < 0.001).…”

Section: De-escalation Strategy For Unresectable Metastasesmentioning

confidence: 99%

Current directions in chemotherapy for colorectal cancer

2006

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vival than chemotherapy alone. From the current regimens, no clear choice can be made that provides any given patient with an optimal chance for a curative treatment or prolonged survival with the fewest side effects.In this article, we review current directions in the conceptual revolution of cancer chemotherapy, and clinical applications of current chemotherapy for advanced CRC. In addition, the proper use of treatment options, such as timing of chemotherapy, combination or sequential therapy, preference of agents for first-line treatment, oral fluoropyrimidines, and combination of local therapies, especially for unresectable disease, are reviewed. Conceptual revolution of cancer chemotherapyThe treatment of cancer is currently undergoing a conceptual revolution owing to the discovery of cancer pathways and the mechanisms of oncogenesis. There are presently two complementary approaches to cancer chemotherapy: conventional chemotherapy, aimed at inhibiting cellular proliferation, and having cytotoxic properties; and targeted therapy, aimed at inhibiting specific targets such as angiogenesis, and having generally cytostatic properties. We shall begin by reviewing this conceptual revolution of cancer chemotherapy for CRC. Cytotoxic chemotherapyCytotoxic antiproliferative agents are still the mainstay of therapy for advanced cancer, including CRC. Based on in vitro experiments with cell lines derived from mice with leukemia, the model of log-dose survival curves for cancer-cell kill, valid for non-cell-cycle-phase-specific cytotoxic agents, became the leading model for chemotherapy dose calculations. 9,10 Consequently, the most

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Pharmacologic Studies of Hepatic Intra-Arterial Chemotherapy

Cited by 69 publications

References 15 publications

Systemic blood levels after intra-arterial administration of microencapsulated mitomycin C in cancer patients

Systemic blood levels after intra-arterial administration of microencapsulated mitomycin C in cancer patients

Surgery After Downstaging of Unresectable Hepatic Tumors With Intra-Arterial Chemotherapy

Current directions in chemotherapy for colorectal cancer

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