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Published in: Cancer Chemotherapy and Pharmacology 5/2009

01-04-2009 | Original Article

A pharmacologic analysis of intraoperative intracavitary cancer chemotherapy with doxorubicin

Authors: Kurt Van der Speeten, O. A. Stuart, H. Mahteme, P. H. Sugarbaker

Published in: Cancer Chemotherapy and Pharmacology | Issue 5/2009

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Abstract

Purpose

A pharmacologic analysis of intracavitary doxorubicin in the treatment of patients with intracavitary cancer dissemination was performed to further evaluate the possible benefits of this treatment modality.

Methods

Twenty appendiceal malignancy patients with peritoneal carcinomatosis (PC), three appendiceal malignancy patients with direct extension into the pleural cavity, 20 patients with peritoneal mesothelioma and one patient with pleural mesothelioma were available for pharmacologic monitoring. After intraperitoneal or intrapleural administration of doxorubicin, plasma and peritoneal fluid samples were obtained at 15, 30, 45, 60 and 90 min in all patients. After intrapleural administration, plasma and pleural fluid samples were collected at similar intervals. Tumor and normal tissues were obtained when available. Doxorubicin concentrations were determined by high-performance liquid chromatography (HPLC).

Results

Intraperitoneal doxorubicin showed a prolonged retention in the peritoneal cavity. Doxorubicin concentrations in tumor tissue were consistently elevated above intraperitoneal concentrations from 30 through 90 min. For appendiceal malignancy, the concentrations of doxorubicin were significantly higher in minimally aggressive mucinous tumors. Pleural chemotherapy solutions retained doxorubicin to a greater extent than peritoneal fluid.

Conclusions

Doxorubicin shows characteristics favorable for intracavitary administration with sequestration of doxorubicin in cancer nodules.
Literature
1.
go back to reference Zoetmulder FA (1982) Modelstudies over het colorectale carcinoom. Amsterdam, Rodopi Zoetmulder FA (1982) Modelstudies over het colorectale carcinoom. Amsterdam, Rodopi
2.
go back to reference Sugarbaker PH, Cunliffe WJ, Belliveau J et al (1989) Rationale for integrating early postoperative intraperitoneal chemotherapy into the surgical treatment of gastrointestinal cancer. Semin Oncol 16(4):83–97PubMed Sugarbaker PH, Cunliffe WJ, Belliveau J et al (1989) Rationale for integrating early postoperative intraperitoneal chemotherapy into the surgical treatment of gastrointestinal cancer. Semin Oncol 16(4):83–97PubMed
5.
go back to reference Alberts DS, Liu PY, Hannigan EV et al (1996) Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335(6):1950–1955PubMedCrossRef Alberts DS, Liu PY, Hannigan EV et al (1996) Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med 335(6):1950–1955PubMedCrossRef
6.
go back to reference Markman M, Bundy BN, Alberts DS et al (2001) Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Oncology Group. J Clin Oncol 19(4):1001–1007PubMed Markman M, Bundy BN, Alberts DS et al (2001) Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Oncology Group. J Clin Oncol 19(4):1001–1007PubMed
7.
go back to reference Armstrong DK, Bundy B, Wenzel L et al (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354(1):34–43PubMedCrossRef Armstrong DK, Bundy B, Wenzel L et al (2006) Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 354(1):34–43PubMedCrossRef
8.
go back to reference Verwaal VJ, Van Ruth S, De Bree E et al (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 21(20):3737–3743PubMedCrossRef Verwaal VJ, Van Ruth S, De Bree E et al (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 21(20):3737–3743PubMedCrossRef
9.
go back to reference Sugarbaker PH (2005) An instrument to provide containment of intraoperative intraperitoneal chemotherapy with optimized distribution. J Surg Oncol 92(2):142–146PubMedCrossRef Sugarbaker PH (2005) An instrument to provide containment of intraoperative intraperitoneal chemotherapy with optimized distribution. J Surg Oncol 92(2):142–146PubMedCrossRef
10.
go back to reference Cummings J, Stuart JFB, Calman KC (1984) Determination of adriamycin, adriamycinol and their 7-deoxyaclycones in human serum by high-performance liquid chromatography. J Chromatogr 311:125–133PubMedCrossRef Cummings J, Stuart JFB, Calman KC (1984) Determination of adriamycin, adriamycinol and their 7-deoxyaclycones in human serum by high-performance liquid chromatography. J Chromatogr 311:125–133PubMedCrossRef
11.
go back to reference Ronnett BM, Zahn CM, Kurman RJ et al (1995) Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis: a clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to “pseudomyxoma peritonei”. Am J Surg Pathol 19(12):1390–1408PubMedCrossRef Ronnett BM, Zahn CM, Kurman RJ et al (1995) Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis: a clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to “pseudomyxoma peritonei”. Am J Surg Pathol 19(12):1390–1408PubMedCrossRef
12.
go back to reference Cerruto CA, Brun EA, Chang D, Sugarbaker PH (2006) Prognostic significance of histomorphologic parameters in diffuse malignant peritoneal mesothelioma. Arch Pathol Lab Med 130(11):1654–1661PubMed Cerruto CA, Brun EA, Chang D, Sugarbaker PH (2006) Prognostic significance of histomorphologic parameters in diffuse malignant peritoneal mesothelioma. Arch Pathol Lab Med 130(11):1654–1661PubMed
14.
go back to reference Hahn GM, Braun J, Har-Kedar I (1975) Thermochemotherapy: synergism between hyperthermia (42–43°) and adriamycin (or bleomycin) in mammalian cell inactivation. Proc Nat Acad Sci 72(3):937–940PubMedCrossRef Hahn GM, Braun J, Har-Kedar I (1975) Thermochemotherapy: synergism between hyperthermia (42–43°) and adriamycin (or bleomycin) in mammalian cell inactivation. Proc Nat Acad Sci 72(3):937–940PubMedCrossRef
15.
go back to reference Lane P, Vichi P, Bain DL et al (1987) Temperature dependence studies of adriamycin uptake and cytotoxocity. Cancer Res 42:4038–4042 Lane P, Vichi P, Bain DL et al (1987) Temperature dependence studies of adriamycin uptake and cytotoxocity. Cancer Res 42:4038–4042
16.
go back to reference Carter SK (1981) Adriamycin—a review. J Natl Cancer Inst 55:1265–1274 Carter SK (1981) Adriamycin—a review. J Natl Cancer Inst 55:1265–1274
17.
go back to reference Johansen PB (1981) Doxorubicin pharmacokinetics after intravenous and intraperitoneal administration in the nude mouse. Cancer Chemother Pharmacol 5:267–270PubMedCrossRef Johansen PB (1981) Doxorubicin pharmacokinetics after intravenous and intraperitoneal administration in the nude mouse. Cancer Chemother Pharmacol 5:267–270PubMedCrossRef
18.
go back to reference Ozols RF, Young RC, Speyer JL et al (1982) Phase I and pharmacological studies of adriamycin administered intraperitoneally to patients with ovarian cancer. Cancer Res 42:4265–4269PubMed Ozols RF, Young RC, Speyer JL et al (1982) Phase I and pharmacological studies of adriamycin administered intraperitoneally to patients with ovarian cancer. Cancer Res 42:4265–4269PubMed
19.
go back to reference Ozols RF, Grotzinger KR, Fisher RI et al (1979) Kinetic characterization and response to chemotherapy in a transplantable murine ovarian cancer. Cancer Res 39:3202–3208PubMed Ozols RF, Grotzinger KR, Fisher RI et al (1979) Kinetic characterization and response to chemotherapy in a transplantable murine ovarian cancer. Cancer Res 39:3202–3208PubMed
20.
go back to reference Ozols RF, Locker GY, Doroshow JH et al (1979) Pharmacokinetics and tissue penetration in murine ovarian cancer. Cancer Res 39:3209–3214PubMed Ozols RF, Locker GY, Doroshow JH et al (1979) Pharmacokinetics and tissue penetration in murine ovarian cancer. Cancer Res 39:3209–3214PubMed
21.
go back to reference Ozols RF, Willson JKV, Weltz MD et al (1980) Inhibition of human ovarian cancer colony formation by adriamycin and its major metabolites. Cancer Res 40:4109–4112PubMed Ozols RF, Willson JKV, Weltz MD et al (1980) Inhibition of human ovarian cancer colony formation by adriamycin and its major metabolites. Cancer Res 40:4109–4112PubMed
22.
go back to reference Sugarbaker PH, Mora JT, Carmignani P, Stuart OA, Yoo D (2005) Update on chemotherapeutic agents utilized for perioperative intraperitoneal chemotherapy. Oncologist 10(2):112–122PubMedCrossRef Sugarbaker PH, Mora JT, Carmignani P, Stuart OA, Yoo D (2005) Update on chemotherapeutic agents utilized for perioperative intraperitoneal chemotherapy. Oncologist 10(2):112–122PubMedCrossRef
23.
go back to reference Roboz J, Jacobs AJ, Holland JF et al (1981) Intraperitoneal infusion of doxorubicin in the treatment of gynecologic carcinomas. Med Pediatr Oncol 9:245–250PubMedCrossRef Roboz J, Jacobs AJ, Holland JF et al (1981) Intraperitoneal infusion of doxorubicin in the treatment of gynecologic carcinomas. Med Pediatr Oncol 9:245–250PubMedCrossRef
24.
go back to reference Yan TD, Welch L, Black D et al (2007) A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann Oncol 18(5):827–834PubMedCrossRef Yan TD, Welch L, Black D et al (2007) A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma. Ann Oncol 18(5):827–834PubMedCrossRef
25.
go back to reference Raspagliesi F, Kusamura S, Campos Torres JC et al (2006) Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: the experience of National Cancer Institute of Milan. Eur J Surg Oncol 32(6):671–675PubMedCrossRef Raspagliesi F, Kusamura S, Campos Torres JC et al (2006) Cytoreduction combined with intraperitoneal hyperthermic perfusion chemotherapy in advanced/recurrent ovarian cancer patients: the experience of National Cancer Institute of Milan. Eur J Surg Oncol 32(6):671–675PubMedCrossRef
26.
go back to reference Yan TD, Black D, Savady R et al (2007) A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Ann Surg Oncol 14(2):484–492PubMedCrossRef Yan TD, Black D, Savady R et al (2007) A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Ann Surg Oncol 14(2):484–492PubMedCrossRef
27.
go back to reference Stelin G, Rippe B (1990) A phenomenological interpretation of the variation in dialysate volume with dwell time in CAPD. Kidney Int 38(3):465–472PubMedCrossRef Stelin G, Rippe B (1990) A phenomenological interpretation of the variation in dialysate volume with dwell time in CAPD. Kidney Int 38(3):465–472PubMedCrossRef
28.
go back to reference Ceelen WP, Påhlman L, Mahteme H (2006) Pharmacodynamic aspects of intraperitoneal cytotoxic therapy. In Peritoneal carcinomatosis: a multidisciplinary approach. Cancer Treat Res, Springer, 195–214 Ceelen WP, Påhlman L, Mahteme H (2006) Pharmacodynamic aspects of intraperitoneal cytotoxic therapy. In Peritoneal carcinomatosis: a multidisciplinary approach. Cancer Treat Res, Springer, 195–214
29.
go back to reference Dedrick RL, Flessner MF (1997) Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst 89(7):480–487PubMedCrossRef Dedrick RL, Flessner MF (1997) Pharmacokinetic problems in peritoneal drug administration: tissue penetration and surface exposure. J Natl Cancer Inst 89(7):480–487PubMedCrossRef
30.
go back to reference Sugarbaker PH, Stuart OA (2007) Pharmacokinetic and phase II study of heated intraoperative intraperitoneal melphalan. Cancer Chemother Pharmacol 59(2):151–155PubMedCrossRef Sugarbaker PH, Stuart OA (2007) Pharmacokinetic and phase II study of heated intraoperative intraperitoneal melphalan. Cancer Chemother Pharmacol 59(2):151–155PubMedCrossRef
Metadata
Title
A pharmacologic analysis of intraoperative intracavitary cancer chemotherapy with doxorubicin
Authors
Kurt Van der Speeten
O. A. Stuart
H. Mahteme
P. H. Sugarbaker
Publication date
01-04-2009
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 5/2009
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-008-0800-0

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