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      Pharmacokinetic Study of Perioperative Intravenous Ifosfamide

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          Abstract

          The use of cancer chemotherapy and hyperthermia as part of a surgical procedure in the management of patients with peritoneal carcinomatosis has gained prominence in recent years with selected patients showing benefit. Patients with peritoneal surface malignancy following cancer resection were treated with intraperitoneal hyperthermic (41.5–42.5°C) cisplatin and doxorubicin combined with the infusion of systemic ifosfamide chemotherapy. The concentrations of ifosfamide and 4-hydroxyifosfamide were determined in plasma, peritoneal fluid, urine, and when possible, within small tumor nodules less than 1 cm. Plasma concentrations of ifosfamide exceeded peritoneal fluid levels of ifosfamide during the 90 minutes of chemotherapy infusion. Both ifosfamide and 4-hydroxyifosfamide could be recovered from peritoneal tumor nodules throughout the 90 minutes of ifosfamide continuous infusion and exceeded plasma concentrations. 4-Hydroxyifosfamide within peritoneal surface cancer nodules suggested a favorable pharmacologic endpoint in the study of ifosfamide administered in the operating room.

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          Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study.

          Dominique Elias, François Gilly, Florent Boutitie … (2010)
          PURPOSE Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. PATIENTS AND METHODS A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. CONCLUSION This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.
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            Complete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin.

            Dominique Elias, Jérémie Lefèvre, Julie Chevalier … (2009)
            To compare the long-term survival of patients with isolated and resectable peritoneal carcinomatosis (PC) in comparable groups of patients treated with systemic chemotherapy containing oxaliplatin or irinotecan or by cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). All patients with gross PC from colorectal adenocarcinoma who had undergone cytoreductive surgery plus HIPEC from 1998 to 2003 were evaluated. The standard group was constituted by selecting patients with colorectal PC treated with palliative chemotherapy during the same period, but who had not benefited from HIPEC because the technique was unavailable in the center at that time. Forty-eight patients were retrospectively included in the standard group and were compared with 48 patients who had undergone HIPEC and were evaluated prospectively. All characteristics were comparable except age and tumor differentiation. There was no difference in systemic chemotherapy, with a mean of 2.3 lines per patient. Median follow-up was 95.7 months in the standard group versus 63 months in the HIPEC group. Two-year and 5-year overall survival rates were 81% and 51% for the HIPEC group, respectively, and 65% and 13% for the standard group, respectively. Median survival was 23.9 months in the standard group versus 62.7 months in the HIPEC group (P < .05, log-rank test). Patients with isolated, resectable PC achieve a median survival of 24 months with modern chemotherapies, but only surgical cytoreduction plus HIPEC is able to prolong median survival to roughly 63 months, with a 5-year survival rate of 51%.
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              Prognostic features of 51 colorectal and 130 appendiceal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery and intraperitoneal chemotherapy.

              Kathleen A Jablonski, P. H. Sugarbaker (1995)
              A treatment plan to be used in patients with peritoneal carcinomatosis was devised and tested as a Phase II study. Peritoneal carcinomatosis from appendical or colorectal cancer has been regarded as a fatal clinical entity. Treatment protocols have not been reported previously. The authors used cytoreductive surgery and intraperitoneal chemotherapy to treat 181 consecutive patients with peritoneal carcinomatosis. There were 51 patients with colorectal cancer and 130 patients with appendiceal cancer. Mean follow-up is 24 months, with a range of 0 to 149 months. Clinical features that showed prognostic significance included appendiceal versus colorectal primary tumors (p = 0.0001), grade 1 versus grades 2 and 3 histopathology (p = 0.0003), complete versus incomplete cytoreductions (p = 0.0001), lymph node-negative versus lymph node-positive primary tumors (p = 0.0001), and volume of peritoneal carcinomatosis present preoperatively for colon cancer (p = 0.0006). Features with no statistical prognostic significance included preoperative tumor volume for appendiceal cancer, age, sex, number of cycles of chemotherapy, operative time, complications, blood loss, and institution providing treatment. From these prognostic features, four prognostic groups were identified, and 3-year survival was estimated by the product-limit survival method. Group I patients (n = 76) were those with grade 1 histology, no lymph node metastases, and complete cytoreductions (survival at 3 years = 99%). Group II patients (n = 23) were those with grade 2 or 3 histology, no lymph node metastases, and complete cytoreductions (65%). Group III patients (n = 24) had any histology, lymph node metastases, and complete cytoreductions (66%). Group IV patients (n = 58) had incomplete cytoreductions (20%).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Surg Oncol
                Journal ID (publisher-id): IJSO
                Title: International Journal of Surgical Oncology
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-1402
                ISSN (Electronic): 2090-1410
                Publication date (Print): 2011
                Publication date (Electronic): 21 September 2011
                Volume: 2011
                Electronic Location Identifier: 185092
                Affiliations
                1Department of Surgical Oncology, Hospital East-Limburg, 3600 Genk, Belgium
                2Washington Cancer Institute, Washington Hospital Center, Washington, DC 20010, USA
                3Division of Surgical Sciences, Department of Surgery, Uppsala University Hospital, 75185 Uppsala, Sweden
                Author notes

                Academic Editor: Wai Lun Law

                Article
                DOI: 10.1155/2011/185092
                PMC ID: 3263669
                PubMed ID: 22312496
                SO-VID: cb80e4ee-7b71-42b8-b1e8-b3534060db99
                Copyright © Copyright © 2011 Kurt Van der Speeten et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 17 March 2011
                Date revision received : 27 June 2011
                Date accepted : 13 July 2011
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Oncology & Radiotherapy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy

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