A pharmacologic analysis of intraoperative intracavitary cancer chemotherapy with doxorubicin
- 150 Downloads
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.
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).
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.
Doxorubicin shows characteristics favorable for intracavitary administration with sequestration of doxorubicin in cancer nodules.
KeywordsIntraperitoneal chemotherapy Intrapleural chemotherapy Doxorubicin Pharmacokinetics Pharmacodynamics Appendiceal cancer Peritoneal mesothelioma Pleural mesothelioma
- 1.Zoetmulder FA (1982) Modelstudies over het colorectale carcinoom. Amsterdam, RodopiGoogle Scholar
- 6.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):1001–1007PubMedGoogle Scholar
- 8.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):3737–3743PubMedCrossRefGoogle Scholar
- 11.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):1390–1408PubMedCrossRefGoogle Scholar
- 15.Lane P, Vichi P, Bain DL et al (1987) Temperature dependence studies of adriamycin uptake and cytotoxocity. Cancer Res 42:4038–4042Google Scholar
- 16.Carter SK (1981) Adriamycin—a review. J Natl Cancer Inst 55:1265–1274Google Scholar
- 28.Ceelen WP, Påhlman L, Mahteme H (2006) Pharmacodynamic aspects of intraperitoneal cytotoxic therapy. In Peritoneal carcinomatosis: a multidisciplinary approach. Cancer Treat Res, Springer, 195–214Google Scholar