| 1. |
- Carlier, Charlotte, et al.
(författare)
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Preclinical activity of melflufen (J1) in ovarian cancer
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:37, s. 59322-59335
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Tidskriftsartikel (refereegranskat)abstract
- Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra-and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.
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| 2. |
- Ceelen, Wim P., et al.
(författare)
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Pharmacodynamic aspects of intraperitoneal cytotoxic therapy
- 2007
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Ingår i: Cancer treatment and research. - 0927-3042. ; 134, s. 195-214
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Tidskriftsartikel (refereegranskat)abstract
- The rationale for ip administration as an adjunct to surgery is firmly based on theoretical and pharmacokinetic grounds. The superiority of combined ip and intravenous chemotherapy over intravenous chemotherapy alone has been established in randomized trials in stage IIIc ovarian cancer patients. Intraoperative ip cytotoxic therapy results in a definite pharmacological advantage, since high peritoneal concentrations are achieved with limited systemic absorption. At present, however, it is not clearly established to what extent this PK advantage will result in enhanced anticancer activity and, ultimately, in a survival benefit. Preclinical models show that direct penetration into tumour tissue is limited to a few millimeters. Furthermore, the limited exposure time of intraoperative chemoperfusion could limit cytotoxic activity despite high local concentrations. Among the cytotoxic agents currently used, the pharmacodynamic aspects of the platinum compounds are the best studied both with and without associated hyperthermia. Newer agents such as the taxanes and the camptothecins appear promising for ip chemoperfusion during or immediately after surgery. Pharmacodynamic aspects of HIPEC needing further preclinical study-including mathematical modeling - are the establishment of tumour tissue penetration of the newer agents and its relation to hyperthermia, the definition of the relative contribution of direct penetration versus vascular supply by absorbed drug, and the efficacy of combined ip and intravenous regimens. Ultimately, however, randomised trials of ip chemotherapy with surgery will have to provide the evidence base to further build upon.
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| 3. |
- van de Vlasakker, Vincent C. J., et al.
(författare)
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The impact of PRODIGE 7 on the current worldwide practice of CRS-HIPEC for colorectal peritoneal metastases : A web-based survey and 2021 statement by Peritoneal Surface Oncology Group International (PSOGI)
- 2021
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Ingår i: European Journal of Surgical Oncology. - : Elsevier. - 0748-7983 .- 1532-2157. ; 47:11, s. 2888-2892
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC.Materials and methodsCRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7.ResultsThe survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate.ConclusionThe PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated.
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