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Ann Thorac Surg 1995;60:1390-1394
© 1995 The Society of Thoracic Surgeons

Original Articles: General Thoracic

Pulmonary Artery Perfusion of Doxorubicin With Blood Flow Occlusion: Pharmacokinetics and Treatment in a Metastatic Sarcoma Model

Hong-Yue Wang, MD, Bruce Ng, MS, David Blumberg, MD, Jeffrey L. Port, MD, Steven N. Hochwald, MD, Michael E. Burt, MD, PhD

Thoracic Oncology Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York

Accepted for publication July 12, 1995.


   Abstract
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 Footnotes
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
Background. We compared pharmacokinetics, toxicity, and treatment efficacy of pulmonary artery perfusion of low-dose doxorubicin with blood flow occlusion to intravenous doxorubicin injection in a metastatic sarcoma model in the rat.

Methods. Animals received left pulmonary artery perfusion with 0.1, 0.2, or 0.5 mg/kg doxorubicin at a rate of 0.1 mL/min for 1 minute with 20 minutes of blood flow occlusion. Doxorubicin levels of the lung, heart, and serum were assayed. Body weights after treatment were recorded and right pneumonectomy was performed. The results were compared with those in rats that received 5 mg/kg doxorubicin by intravenous injection or the saline group. Pulmonary sarcoma metastases were treated with 0.5 mg/kg doxorubicin through lung perfusion or intravenously, or with saline solution.

Results. Doxorubicin levels in the lung, heart, and serum were 112.1 ± 9.2 µg/g, 1.7 ± 0.2 µg/g, and 0.3 ± 0.1 µg/mL in the group with 0.5 mg/kg doxorubicin perfusion, versus 24.8 ± 1.9 µg/g, 10.1 ± 1.3 µg/g, and 0.7 ± 0.2 µg/mL in the intravenous group (p < 0.05). Animals had normal growth patterns and survived after right pneumonectomy in the perfused group, whereas the intravenous group failed to thrive. No tumors were found or a significant reduction in nodules was noted in the lungs treated with perfusion as compared with untreated right lungs or the intravenous and saline groups.

Conclusion. This chemotherapy model has important pharmacokinetic advantages and causes an increased treatment response for pulmonary metastatic sarcoma with minimal systemic and local toxicity as compared with systemic doxorubicin administration.


   Introduction
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 Abstract
 Introduction
Material and Methods
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See also page 1394.

Management of pulmonary metastases remains a major clinical problem. Surgical resection has demonstrated benefit, yet 5-year survival after surgery alone ranges from 15% to 25% [1, 2]. To date, systemic chemotherapy for metastatic pulmonary sarcoma holds little promise for long-term survival. Doxorubicin is the most effective single agent in the treatment of soft-tissue sarcoma; however, its toxicity, especially cardiotoxicity, precludes effective therapy [3]. To investigate less invasive modalities for the treatment of pulmonary metastases, we developed a regional chemotherapeutic model of pulmonary artery perfusion with blood flow occlusion in the rat.

The objectives of this study were as follows: (1) to measure lung, heart, and plasma concentrations of doxorubicin after doxorubicin pulmonary artery perfusion with blood flow occlusion as compared with systemic administration of doxorubicin, (2) to evaluate local lung and systemic toxicity, and (3) to evaluate the efficacy of pulmonary artery perfusion with doxorubicin for pulmonary metastatic sarcoma.


   Material and Methods
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 Abstract
 Introduction
 Material and Methods
Results
 Comment
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Animal Care
Experiments were carried out on Fischer 344 male rats weighing 200 to 250 g (Charles River, Kingston, NY). Animals were treated in accordance with the Animal Welfare Act and the National Institutes of Health ``Guidelines for the Care and Use of Laboratory Animals'' (NIH publication 85-23, revised 1985). All animals had free access to standard laboratory rat food (Rat Chow; Ralston-Purina, St. Louis, MO) and water ad libitum. Housing was temperature controlled with 12-hour light and dark cycles.

Preparation of Tumor Cells
The tumor is a methylcholanthrene-induced sarcoma (MCA) that has been serially passed subcutaneously in the flank of F344 rats and is well characterized [4–6]. The tumor undergoes rapid growth and invades locally after subcutaneous implantation. Pulmonary metastases are induced in a reproducible fashion after intravenous injection of a single cell suspension of MCA sarcoma cells [7]. Animals have microscopic presence of pulmonary metastases on day 7 after tumor inoculation.

Pulmonary Artery Perfusion With Blood Flow Occlusion
Animals were anesthetized with 50 mg/kg of pentobarbital intraperitoneally. The trachea was intubated with a 16F intravenous catheter over a guidewire, and ventilation was maintained with a volume ventilator (Rodent Ventilator model 683; Harvard Apparatus, South Natick, MA) at 70 to 80 strokes/min with a tidal volume of 10 mL/kg. A left thoracotomy was performed through the fourth intercostal space. Using an operating microscope (Karl Zeiss OpMi-1, Wotan, Germany), we clamped the left pulmonary artery proximally and cannulated it distally with a PE-10 catheter (Clay-Adams, Parsippany, NJ). The left lung was perfused for 1 minute at a rate of 0.1 mL/min with a syringe pump (KDS model 200, Boston, MA). Total volume infused was 0.1 mL. The volume that would provide local treatment without systemic leak was determined in previous experiments using different volumes of trypan blue. When 0.1 mL trypan blue was given, the lung was evenly and slowly stained blue from the hilus to the periphery without systemic leak. Twenty minutes of pulmonary artery occlusion was chosen based on previous work, which has shown that after 20 minutes of doxorubicin perfusion, lung doxorubicin concentrations reach equilibrium [8]. After pulmonary artery perfusion and occlusion, the pulmonary artery catheter was removed, the artery was repaired with 9-0 monofilament nylon suture (Ethicon, Plainfield, NJ), and the pulmonary circulation was restored. Venous drainage was not obstructed during the procedure.

Experiment 1—Pharmacokinetics
This experiment was designed to evaluate the pharmacokinetics of pulmonary artery perfusion with blood flow occlusion. Twenty-eight rats were randomized into four groups of 7 animals each. Groups I, II, and III received 0.1, 0.2, and 0.5 mg/kg of doxorubicin, respectively, through the pulmonary artery perfusion with occlusion technique; group IV received 5 mg/kg of doxorubicin through a left external jugular vein cutdown. Groups I, II, and III were sacrificed after 20 minutes of blood flow occlusion and 5 minutes of blood flow restoration. Group IV was sacrificed 25 minutes after receiving doxorubicin intravenously. Blood was collected by abdominal aortic puncture for plasma doxorubicin levels, and the left lungs and hearts were excised. Doxorubicin concentrations were measured by high-performance liquid chromatography as described previously [9].

Experiment 2—Toxicity
This experiment was performed to compare the systemic and local toxicity of doxorubicin delivered by pulmonary artery perfusion with systemic administration. Twenty-four rats were randomized into three groups: pulmonary artery doxorubicin perfusion (PA; n = 12), intravenous doxorubicin injection (IV; n = 6), and sham control (control; n = 6). On day 0, all animals underwent two operative procedures: external jugular vein cutdown and pulmonary artery perfusion. The PA group was perfused with 0.5 mg/kg doxorubicin at a rate of 0.1 mL/min for 1 minute after 20 minutes' occlusion and had a sham intravenous injection with 0.9% saline. The IV group received an intravenous injection of 5 mg/kg doxorubicin and a sham pulmonary artery perfusion; the control group received both a sham intravenous injection and sham pulmonary artery perfusion with 0.9% saline solution. After the pulmonary circulation was restored, a chest tube was inserted and the animals were allowed to survive. Daily weights were recorded for all groups for 21 days. To determine pulmonary doxorubicin toxicity on the perfused left lung, we performed a contralateral pneumonectomy in the PA group. If the animal survived after pneumonectomy, we reasoned that the perfused lung was functioning relatively normally. On day 21, right pneumonectomy was performed on 10 rats in the PA group. Two rats from the PA group and 2 rats from the control group were sacrificed, and their left lungs were excised for histologic analysis.

Experiment 3—Efficacy
This experiment was designed to evaluate the effectiveness of pulmonary artery perfusion of doxorubicin in an experimental pulmonary metastatic sarcoma model. On day 0, 24 animals had an intravenous injection of 107 viable MCA sarcoma cells through the right external jugular vein to produce pulmonary metastases. On day 7 after tumor inoculation, the animals were randomized into three groups: pulmonary artery perfusion with 0.5 mg/kg doxorubicin (PA; n = 8), pulmonary artery perfusion with 0.9% saline solution (NS; n = 8), and intravenous injection of 0.5 mg/kg doxorubicin (IV; n = 8). The pulmonary artery perfusion with occlusion technique was performed as described previously. On day 14 all animals were sacrificed, and the lungs were stained for identification of pulmonary sarcoma nodules [10].

Data Analysis
All data are presented as mean ± standard deviation. Analysis of variance was used for data analysis. Significance was defined as p less than 0.05.


   Results
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 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Experiment 1
Lung, heart, and plasma doxorubicin concentrations for the four groups are listed in Table 1Go. Lung doxorubicin levels in the pulmonary artery perfusion groups were dose dependent. In group I (pulmonary artery perfusion with 0.1 mg/kg doxorubicin), 2% of the dose of doxorubicin compared with group IV (intravenous 5 mg/kg doxorubicin) was delivered, yet the lung doxorubicin levels were similar to those in group IV, whereas heart and serum doxorubicin levels were much lower. In groups II and III, doxorubicin doses delivered were 4% and 10%, respectively, of those in group IV, but lung doxorubicin levels were significantly elevated whereas heart and plasma doxorubicin levels were reduced.


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  		Table 1. . Final Lung, Heart, and Serum Doxorubicin Concentrations After Pulmonary Artery Perfusion or Intravenous Administration
 
Experiment 2
After operation, all animals lost weight for the first 2 to 3 days. Afterward, the pulmonary artery doxorubicin perfusion (PA) and control groups resumed normal growth curves, gaining weight daily. However, in the intravenous doxorubicin (IV) group, the growth curve reached a plateau and the animals failed to gain weight normally after treatment. One animal died in the IV group; all other animals survived after doxorubicin or 0.9% saline perfusion. Daily weights during the study period are depicted in Figure 1Go.



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  		Fig 1. . Daily weights of animals with 0.5 mg/kg of doxorubicin by pulmonary artery perfusion (PA), 5 mg/kg of doxorubicin by intravenous injection (IV), and 0.9% saline solution by pulmonary artery perfusion (CTL).

 
Right pneumonectomy was performed on 10 animals in the PA group on day 21 after pulmonary artery perfusion to assess the function of the perfused left lung. Seven of 10 animals survived the procedure, for a survival rate of 70%.

Histologic analysis of lung samples in the PA and control groups demonstrated mild to moderate multifocal interstitial thickening with mild mononuclear cell infiltrate and multifocal pleural and subpleural granulomatous inflammation (Fig 2a, 2bGoGo). No significant differences were seen between the PA and control groups.




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  		Fig 2. . (A) Left lung histology on day 21 after lung perfusion with 0.9% saline solution showing moderate multifocal pleural and subpleural granulomatous inflammation, multifocal interstitial thickening with mononuclear cell infiltrate, very mild emphysema, and hemorrhage. (B) Left lung histology on day 21 after lung perfusion with 0.5 mg/kg doxorubicin. Multifocal pleural and subpleural granulomatous inflammation is mild to moderate. Multifocal interstitial thickening is present with mild mononuclear cell infiltrate. There is mild scattered hemorrhage and emphysema.

 
Experiment 3
Pulmonary artery perfusion with 0.9% saline or intravenous injection of 0.5 mg/kg doxorubicin had no effect on tumor growth. In both groups, there was massive bilateral pulmonary tumor infiltration (mean number of left or right lung nodules greater than 100). Four of 8 animals in the pulmonary artery perfusion group (0.5 mg/kg doxorubicin) had a significant reduction in pulmonary nodules in the left perfused lung (mean 6 ± 4 left lung nodules); the other 4 had complete responses to pulmonary artery perfusion therapy. In contrast, the untreated right lungs were completely replaced by tumor (mean number of lung nodules greater than 100) (Fig 3Go).



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  		Fig 3. . From left: normal lung, lung after 0.5 mg/kg doxorubicin (DOX) intravenous injection (IV), lung after pulmonary artery perfusion (PA) with 0.9% saline solution (NS); and perfusion with 0.5 mg/kg doxorubicin. Normal lung tissue stained black; tumor nodules stained white. The left lung was clear of tumor after doxorubicin lung perfusion, whereas the right lung was completely infiltrated by metastatic tumor. Perfusion with saline solution and intravenous injection showed no effect.

 

   Comment
Top
 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
Soft-tissue sarcomas metastasize almost exclusively to the lung. Besides surgical resection, combination chemotherapy has been implemented in the treatment of metastatic pulmonary sarcoma. Doxorubicin-based regimens have proved to be the most effective; however, associated cardiotoxicity has limited their systemic use [3, 11, 12]. The new treatment modalities of regional chemotherapy must be investigated.

Regional chemotherapy by pulmonary artery injection of antineoplastic agents (nitrogen mustard) was used to treat primary lung cancer in the early 1960s. Very few patients were treated with this therapy, yet some had clinical improvement [13, 14]. The feasibility of occluding the pulmonary artery by a balloon catheter has been demonstrated [15]. However, the lack of transplantable pulmonary tumor models has prevented further evaluation of the efficacy of this treatment.

To address the clinical problem of systemic toxicity of chemotherapy, we have developed a technique of pulmonary artery perfusion with blood flow occlusion. This technique holds the promise of delivering high-dose local chemotherapy without adverse systemic exposure. In general, pulmonary metastases derive their blood supply primarily from the pulmonary circulation or from both the pulmonary and bronchial circulations. Very few lesions derive their blood supply from the bronchial circulation alone [14, 16–18]. Therefore, when chemotherapeutic agents are delivered through the pulmonary artery, most metastatic tumors can be targeted. Nevertheless, drugs injected into the pulmonary artery are diluted rapidly and driven out of the pulmonary circulation before sufficient amounts of the chemotherapeutic agents can diffuse into lung parenchyma. The technique of pulmonary artery blood flow occlusion, together with a suitable perfusion volume, may overcome these undesirable events. Pulmonary artery blood flow occlusion also may inhibit the growth of metastatic tumors [19]. Therefore, delivery of chemotherapeutic agents through the pulmonary artery with temporary blood flow occlusion offers a rational approach for the treatment of pulmonary metastatic disease.

In our study, regional delivery of 0.5 mg/kg doxorubicin (one tenth of the intravenous dose) through the pulmonary artery resulted in a fivefold increase in lung tissue doxorubicin levels compared with intravenous (5 mg/kg) doxorubicin injection. On the other hand, cardiac tissue doxorubicin levels were reduced sixfold compared with intravenous injection. Lung tissue doxorubicin levels were dose dependent in this model. Lung doxorubicin concentrations can be further increased with escalating doses of doxorubicin; however, local lung toxicity may also increase.

Pulmonary artery perfusion with blood flow occlusion offers the advantage of delivering an antineoplastic agent regionally while minimizing systemic toxicity. Daily weights reflect the animal's overall health and growth pattern. Animals that underwent pulmonary artery perfusion had a normal growth pattern similar to that in the sham control group. In addition, 70% of these animals survived contralateral pneumonectomy, indicating that the perfused lung functioned relatively normally. However, histologic changes noted in the perfused lung may be attributed to perfusion injury or subclinical infection, as the control group perfused with 0.9% saline also had similar histologic changes.

In this study, we demonstrated that the increased pulmonary levels of doxorubicin attained with pulmonary artery perfusion with blood flow occlusion offer advantages over systemic therapy in the treatment of pulmonary metastases. Intravenous administration of 0.5 mg/kg doxorubicin and pulmonary artery perfusion with 0.9% saline had no antitumor effect on massive bilateral pulmonary tumor infiltration. However, a significant reduction in the number of tumor nodules was seen in all left lungs treated with doxorubicin (0.5 mg/kg) using pulmonary artery perfusion with occlusion. In fact, 4 of the 8 animals had a complete response in the treated lung.

Recently, there has been increased interest in research of isolated lung perfusion. The data have shown that isolated lung perfusion is pharmacokinetically superior to systemic administration and causes an increased treatment response in animal models [9, 20–23]. Similar to isolated lung perfusion, pulmonary artery perfusion with blood flow occlusion offers pharmacokinetic and treatment advantages over intravenous injection. With the use of an intrapulmonary artery balloon catheter for pulmonary artery blood flow block and drug delivery, this technique would offer the following potential benefits: (1) It is relatively safe and simple, and would not require thoracotomy; (2) the positions and time of pulmonary artery blockade can be adjusted as necessary; (3) very small perfusate volumes can be delivered to the lung, avoiding the potential for pulmonary edema; and (4) most metastatic tumors in the lung are bilateral, and both lungs can be treated synchronously and repeatedly.

In summary, small doses of doxorubicin administered by pulmonary artery perfusion with blood flow occlusion significantly elevated lung doxorubicin levels and were associated with reduced heart and serum levels. Systemic and local toxicities were minimal compared with routine intravenous doses of doxorubicin. Finally, there was a significant tumoricidal effect on metastatic pulmonary sarcoma in this model. This technique holds promise for offering a convenient, flexible, and effective treatment modality, useful in the treatment of metastatic pulmonary disease.


   Footnotes
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 Footnotes
Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 
Address reprint requests to Dr Burt, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021.


   References
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 Footnotes
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Lanza LA, Putman JB Jr, Benjamin RS, Roth JA. Response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases. Ann Thorac Surg 1991;51:219–24.[Abstract]
  2. Martini N, McCormack PM, Bains MS, Beattie EJJ. Surgery for solitary and multiple pulmonary metastases. NY State J Med 1978;78:1711–3.[Medline]
  3. Casper ES, Gaynor JJ, Hajdu SI, et al. A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high-grade extremity soft tissue sarcoma and an analysis of prognostic factors. Cancer 1991;68:1221–9.[Medline]
  4. Burt M, Lowry SF, Gorschboth C, Brennan MF. Metabolic alterations in a noncachectic animal tumor system. Cancer 1981;47:2138–46.[Medline]
  5. Nagashima A, Yasumoto K, Nakahashi H, Furukawa T, Inokuchi K, Nomoto K. Establishment and characterization of high and low-metastatic clones derived from a methylcholanthrene-induced rat fibrosarcoma. Cancer Res 1986;46:4420–4.
  6. Popp MB, Morrison SD, Brennan MF. Total parenteral nutrition in a methylcholanthrene-induced rat sarcoma model. Cancer Treat Rep 1981;65:137–43.
  7. Madden RE, Burk D. Production of viable single cell suspension from solid tumors. J Natl Cancer Inst 1961;27:841–61.
  8. Minchin RF, Boyd MR. Uptake and metabolism of doxorubicin in isolated perfused rat lung. Biochem Pharmacol 1983;32:2829–32.[Medline]
  9. Weksler B, Ng B, Lenert J, Burt M. Isolated single lung perfusion with doxorubicin is pharmacokinetically superior to intravenous injection. Ann Thorac Surg 1993;56:209–14.[Abstract]
  10. Wexler H. Accurate identification of experimental pulmonary metastases. J Natl Cancer Inst 1966;36:641–5.
  11. Benjamin RJ, Wiernik PH, Bachur NR. Adriamycin: a new effective agent in the therapy of disseminated sarcoma. Med Pediatr Oncol 1975;1:63–9.[Medline]
  12. Gottlieb JA, Baker LH, O'Bryan RM, et al. Adriamycin (NSC-123127) used alone and in combination for soft tissue and bony sarcomas. Cancer Chemother Rep 1975;6:271–82.
  13. Morris JF. Chemotherapy of brochogenic carcinoma utilizing cardiac catheterization. Am J Med Sci 1961;242:527–33.
  14. Smyth NP, Blades B. Selective chemotherapy of the lung during unilateral pulmonary arterial occlusion with a balloon-tipped catheter. J Thorac Cardiovasc Surg 1960;40: 653–66.
  15. Karakousis CP, Park HC, Sharma SD, Kanter P. Regional chemotherapy via the pulmonary artery for pulmonary metastases. J Surg Oncol 1981;18:249–55.[Medline]
  16. Miller BJ, Rosenbaum AS. The vascular supply to metastatic tumors of the lung. Surg Gynecol Obstet 1967;125:1009–12.[Medline]
  17. Milne ENC. Circulation of primary and metastatic pulmonary neoplasms. Radiology 1967;100:603–19.[Medline]
  18. Milne ENC, Noonan CD, Margulis AR, Stoughton JA. Vascular supply of pulmonary metastases. Invest Radiol 1969;4:215–29.[Medline]
  19. Wang HY, Ng B, Ahrens C, Burt M. Unilateral pulmonary artery occlusion inhibits growth of pulmonary metastatic sarcoma in the rat. J Surg Oncol 1994;57:183–6.[Medline]
  20. Weksler B, Lenert J, Ng B, Burt M. Isolated single lung perfusion with doxorubicin is effective in eradicating soft tissue sarcoma lung metastases in a rat model. J Thorac Cardiovasc Surg 1994;107:50–4.[Abstract/Free Full Text]
  21. Minchin RF, Johnston MR, Aiken MA, Boyd MR. Pharmacokinetics of doxorubicin in isolated dogs and humans perfused in vivo. J Pharmacol Exp Ther 1984;229:193–8.[Abstract/Free Full Text]
  22. Pogrebniak HW, Witt CJ, Terrill R, et al. Isolated lung perfusion with tumor necrosis factor: a swine model in preparation of human trials. Ann Thorac Surg 1994;57: 1477–83.[Abstract]
  23. Cowen ME, Howard RB, Noker PE, et al. Dose-related doxorubicin effect in an orthotopic secondary lung cancer screen. J Surg Res 1994;56:295–301.[Medline]

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