Regional chemotherapy via the pulmonary artery for pulmonary metastases

Karakousis, Constantine P.; Park, H. C.; Sharma, Shraddha; Kanter, Peter M.

doi:10.1002/jso.2930180305

Cited by 18 publications

(10 citation statements)

References 15 publications

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“…Finally, flow reduction during SPAP resulted in inhomogeneous distribution. Based upon these conclusions, we now chose to perfuse the lung with intact pulmonary circulation followed by BFO, and not during BFO, in contrast to all published SPAP studies in the last 25 years [6][7][8][9][10][11].…”

Section: Discussionmentioning

confidence: 89%

“…Selective pulmonary artery perfusion is an experimental treatment modality of regional chemotherapy delivering higher locoregional cytostatic drug concentrations with minimal systemic drug concentrations and thus minimal side-effects [5][6][7][8]. As a relatively safe and simple non-surgical procedure, SPAP has the advantage over ILuP of allowing repeated regional chemotherapy with minimal volume administration.…”

Section: Discussionmentioning

confidence: 99%

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Selective pulmonary artery perfusion followed by blood flow occlusion: New challenge for the treatment of pulmonary malignancies

et al. 2009

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Selective pulmonary artery perfusion followed by blood flow occlusion: New challenge for the treatment of pulmonary malignancies

et al. 2009

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“…Furthermore, they achieved lower serum levels compared with i.v. injection, whereas we believe that maximal systemic exposure during SPAP is essential to treat (micro)metastatic disease outside the lungs in lung cancer (Karakousis et al, 1981).…”

Section: Downloaded Frommentioning

confidence: 96%

“…First, Karakousis et al (1981) performed Schwann-Ganz catheterization of lobe branches separately under fluoroscopic control in seven patients with recurrent pulmonary metastases who had already received the maximum dose of adriamycin. They received a dose of 10 to 20 mg diluted in 50 ml infused over a 1-to 2-min period followed by 5 min of blood flow occlusion.…”

Section: Van Putte Et Almentioning

confidence: 99%

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Pharmacokinetics of Gemcitabine when Delivered by Selective Pulmonary Artery Perfusion for the Treatment of Lung Cancer

Putte

Grootenboers²,

Boven

et al. 2008

Drug Metab Dispos

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ABSTRACT:Lung cancer represents a major health problem. Cytostatic and radiotherapeutic treatment is limited because of dose-limiting systemic toxicity and surgery as a result of its invasive nature. Therefore, we developed a catheterization model of selective pulmonary artery perfusion (SPAP) combining the properties of isolated lung perfusion and i.v. treatment to achieve higher local drug levels and equivalent systemic exposure. Sixteen pigs underwent SPAP using a clinically applied dose of gemcitabine (1 g/m 2 ). They furthermore underwent thoracotomy for tissue sampling. Three groups were treated with SPAP for 2 min with normal pulmonary blood flow, 50 and 90% flow reduction. Another group had SPAP for 10 min with normal blood flow. All the SPAP groups underwent catheterization of the left pulmonary artery. An additional group (n ‫؍‬ 4) was infused i.v. for 30 min using the same dose. Concentrations were analyzed with analysis of variance. Pulmonary peak concentrations (p ‫؍‬ 0.01) and areas under the curve (AUC) (p ‫؍‬ 0.001) of SPAP for 2 and 10 min were significantly higher compared with i.v., whereas SPAP for 10 min resulted in the highest AUC (p ‫؍‬ 0.045) compared with SPAP for 2 min. Flow reduction during SPAP resulted in inhomogeneous distribution. Liver levels, AUC (serum), and wet-to-dry ratios of all the SPAP groups were not significantly different compared with i.v. SPAP resulted in higher lung concentrations, whereas systemic exposure was comparable with i.v. Therefore, we advocate SPAP as a new method to be tested clinically to achieve down-staging of the tumor and lymph node status in lung cancer.Cancer is the leading cause of death before the age of 85 years, resulting in more than half a million deaths per year in the United States (Jemal et al., 2006). In 2005, primary lung cancer was the second leading cancer type in the United States with approximately 190,000 new cases to be estimated for 2006. Among all the cancer types, lung cancer has the highest death rate (Jemal et al., 2006).Non-small cell lung cancer (NSCLC) is usually treated by surgical resection, radiotherapy, and/or cytostatic drug administration, depending on the disease stage. Stage 1 (a and b) and 2 (a and b) NSCLCs are currently treated by surgical resection, whereas (adjuvant) cytostatic therapy is applied to stage 1b, 2, and 3 disease, resulting in a 5-year survival of 75, 60, 40, 20, and 15%, respectively (Spiro and Silvestri, 2005).An i.v. infusion is the desired route of cytostatic drug administration to achieve exposure of the primary lung tumor and distant disease, as well as resulting in a 5-year survival benefit of 4 to 14% compared with surgery alone (Betticher, 2005). However, this method is dose-limited by the occurrence of systemic toxicity like bone marrow suppression that limits exposure of the primary tumor and pulmonary (lymph node) metastases.In contrast, isolated lung perfusion with cytostatic drugs is an experimental surgical technique for the treatment of lung metastases that aims to destroy pulmonar...

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Targeted drug delivery

Freeman

Mayhew

1986

Cancer

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Cancer chemotherapy drugs are neither specific, i.e., they do not act exclusively on the metabolic pathways of cancer cells, nor are they targeted solely toward cancer cells. However, recent research has begun to address, in part, the latter issue. Improved delivery of chemotherapeutic agents to tumor tissue in man appears to be an achievable goal in the next decade. Improved drug delivery includes developing predictive models that allow for laboratory assessment of the best treatment for a patient's cancer without exposing the patient to an empirical trial or to the possible morbidity from exposure to a less useful drug, or to the loss of time in the fight against cancer because of ineffectual therapy. Monoclonal antibodies directed against tumor-associated antigens have the potential to achieve major advances in targeted drug delivery. Monoclonal antibodies may have direct antitumor effects, or they can be used as "homing devices" when attached to a payload and can guide diagnostic or therapeutic agents to the targeted tissues. Carrier systems of all types have become available; these include liposomes and polymeric compounds which can carry drugs, radionuclides, toxins, or other materials in a protected environment. These carriers can also be bound to monoclonal antibodies for possible targeted delivery. Pharmacological sanctuaries have been recognized as a problem in cancer treatment. The best known of these is the central nervous system (CNS). Techniques to temporarily disrupt the blood-brain barrier are now appearing. Mechanisms to administer therapy directly into the CNS are also being reassessed. Implantable pumps and reservoirs have been used to treat selected organs or for regional perfusions. Other treatments that are regional in scope include administration directly into a cavity or into a tumor. Computerized implantable devices should play a major role in cancer therapy in the future, in pain control as well as antibiotic and hormone administration. In recent years, mathematical models have been developed that can more accurately predict drug distribution and metabolism in various tissues of the body. Such models point the way to more logical designs of chemotherapeutic administration. The expanded use of autologous bone marrow transplantation, along with improving techniques of "purging" the marrow of tumor cells before reinfusion can be anticipated. Pro-drugs are substances that must be biotransformed in vivo to exert their pharmacologic effect.(ABSTRACT TRUNCATED AT 400 WORDS)

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Regional chemotherapy via the pulmonary artery for pulmonary metastases

Cited by 18 publications

References 15 publications

Selective pulmonary artery perfusion followed by blood flow occlusion: New challenge for the treatment of pulmonary malignancies

Selective pulmonary artery perfusion followed by blood flow occlusion: New challenge for the treatment of pulmonary malignancies

Pharmacokinetics of Gemcitabine when Delivered by Selective Pulmonary Artery Perfusion for the Treatment of Lung Cancer

Targeted drug delivery

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