Point: Intraperitoneal Chemotherapy in the Management of Ovarian Cancer

2004 ◽  
Vol 2 (6) ◽  
pp. 549-554 ◽  
Author(s):  
Maurie Markman
Keyword(s):  
Ovarian Cancer ◽  
Small Volume ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Rational Approach ◽  
Pharmacokinetic Studies ◽  
Phase Ii Trials ◽  
Intraperitoneal Therapy ◽  
Phase Iii Trials ◽  
Optimal Approach

Both preclinical considerations and results of phase I safety and pharmacokinetic studies provided support for the argument that intraperitoneal antineoplastic drug delivery should be a rational approach to the management of ovarian cancer. Subsequently conducted phase II trials exploring regional treatment revealed surgically documented objective responses when the approach was employed as a second-line therapy. Recently, the results of three randomized phase III trials have shown that the use of primary cisplatin-based intraperitoneal therapy leads to superior survival compared with intravenous cisplatin-based treatment in patients with small-volume residual advanced ovarian cancer after initial surgical cytoreduction. Further exploration of this unique management strategy is indicated to develop an optimal approach that maintains the demonstrated enhanced efficacy while reducing the toxicity (principally because of cisplatin) of treatment.

Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin.

1991 ◽  
Vol 9 (10) ◽  
pp. 1801-1805 ◽  
Author(s):  
M Markman ◽  
B Reichman ◽  
T Hakes ◽  
W Jones ◽  
J L Lewis ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Small Volume ◽  
Recurrent Ovarian Cancer ◽  
Second Line ◽  
Front Line ◽  
Phase Ii Trials ◽  
Two Phase ◽  
Overall Response ◽  
Intraperitoneal Therapy

Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front-line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer.

scholarly journals First-line PARP inhibitors in ovarian cancer: summary of an ESMO Open - Cancer Horizons round-table discussion

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e001110
Author(s):  
Susana Banerjee ◽  
Antonio Gonzalez-Martin ◽  
Philipp Harter ◽  
Domenica Lorusso ◽  
Kathleen N Moore ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Parp Inhibitor ◽  
Advanced Ovarian Cancer ◽  
Round Table ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
European Medicines Agency ◽  
First Line ◽  
Phase Iii Trials

Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is the latest breakthrough in the management of newly diagnosed advanced ovarian cancer. The results of the SOLO-1 trial in 2018 led to European Medicines Agency and Food and Drug Administration approval of olaparib as first-line maintenance therapy in patients with BRCA1/2 mutation, establishing a new standard of care. Subsequently, the results of three phase III trials (PRIMA, PAOLA-1, VELIA) evaluating the use of first-line PARP inhibitors beyond patients with BRCA1/2 mutations and as combination strategies were presented in 2019, leading to the recent approval of maintenance niraparib irrespective of biomarker status and olaparib in combination with bevacizumab in homologous recombination deficiency-positive-associated advanced ovarian cancer. An ESMO Open - Cancer Horizons round-table expert panel discussed the four phase III trials of first-line PARP inhibitor therapy and how they are changing the clinical management of advanced ovarian cancer.

Where have we gone wrong? Phase II trials (Ph2t) do not inform the results of phase III trials (Ph3t) in platinum resistant ovarian cancer (PROC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5559-5559 ◽  
Author(s):  
Tami Grunewald ◽  
Monica Tang ◽  
Julia Chen ◽  
Sally Lord ◽  
Michael Friedlander ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Platinum Resistant ◽  
Phase Iii Trials

Principles and practice of intraperitoneal chemotherapy for ovarian cancer

2007 ◽  
Vol 17 (1) ◽  
pp. 1-20 ◽  
Author(s):  
K. Fujiwara ◽  
D. Armstrong ◽  
M. Morgan ◽  
M. Markman
Keyword(s):  
Ovarian Cancer ◽  
Survival Benefit ◽  
Meta Analysis ◽  
Gynecologic Oncology ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Clinical Aspects ◽  
Gynecologic Oncology Group ◽  
Oncology Group ◽  
Phase Iii Trials

Intraperitoneal (IP) chemotherapy has been studied for years to improve the survival of patients with ovarian cancer. Recently, the result of Gynecologic Oncology Group 172 trial comparing IP versus intravenous administration of cisplatin-based chemotherapy was published, demonstrating the improvement of survival benefit in favor of the IP arm. This trial is the third trial that showed a survival benefit on IP chemotherapy. The National Cancer Institute (NCI) and Gynecologic Oncology Group have done a meta-analysis on the results of these three US trials and other phase III trials of IP versus intravenous chemotherapy, and significant improvement of survival was shown with IP therapy. Based on this meta-analysis, NCI has released a clinical announcement encouraging the gynecological oncology community to consider IP chemotherapy as the standard treatment for optimally debulked advanced ovarian cancer patients. However, there still are controversial issues regarding the use of IP chemotherapy. It is important to understand how IP chemotherapy works to solve those issues in the future. In this review article, we discuss the principles and clinical aspects of IP chemotherapy and also discuss the current problems and future perspectives in IP chemotherapy

Future options for first-line therapy of advanced ovarian cancer

2005 ◽  
Vol 15 (Suppl 1) ◽  
pp. 42-50 ◽  
Author(s):  
A. Du Bois ◽  
J. Pfisterer
Keyword(s):  
Ovarian Cancer ◽  
Standard Therapy ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Current Standard ◽  
Two Phase

The current standard of treatment for patients with advanced ovarian cancer has been established in light of the results from various clinical trials. After debulking surgery, a combination of carboplatin and paclitaxel is considered to be the best treatment option in terms of survival and quality of life. However, since most patients on this chemotherapy modality will experience relapse, several studies have explored, and continue to do so, various modifications and alternatives to standard therapy in order to attain improved efficacy. Various modifications of dose, schedule, or route of standard regimens have shown no benefit, apart from intraperitoneal therapy, which has produced mixed results and would benefit from a definitive trial. Studies of maintenance/consolidation therapy have been mainly negative, although a small number of trials have produced enough positive data to prompt two new studies powered to detect survival benefits. Various phase II trials have investigated “targeted therapies,” but until now no positive results have been recorded. Translational studies are needed to identify patients who will benefit from such specific treatment strategies. The current most evaluated modification of standard therapy is the addition of a third non–cross-resistant drug to carboplatin and paclitaxel. Data for the addition of anthracyclines have either been negative (epirubicin) or not yet analyzed (pegylated liposomal doxorubicin), while evaluable data are shortly expected for the addition of topotecan. Data on the addition of gemcitabine are eagerly awaited from two phase III trials.

scholarly journals Pegylated Liposomal Doxorubicin in the Management of Ovarian Cancer

2010 ◽  
Vol 2 ◽  
pp. CMT.S4456
Author(s):  
Gabriella Ferrandina ◽  
Marco Petrillo ◽  
Angelo Licameli ◽  
Gilda Fuoco ◽  
Giovanni Scambia ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Liposomal Doxorubicin ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Phase Iii ◽  
Line Treatment ◽  
Front Line ◽  
Clinical Role ◽  
High Responsiveness ◽  
Phase Iii Trials

Despite the cytoreductive efforts, and the high responsiveness to standard carboplatin/pacllitaxel front-line treatment, ovarian cancer (OvCa) remains the most lethal gynaecological malignancy with a 5-yr overall survival of only 25%–30% in advanced stage disease. Among the pharmaceutical options available for treatment of OvCa, much attention has been dedicated to pegylated liposomal doxorubicin (PLD) (Doxil® in the US; Caelyx® in Canada and Europe); this drug has a unique formulation which has entrapped conventional doxorubicin in a bilayer lipidic sphere surrounded by a polyethylene glycol layer, which prolongs the persistence of the drug in the circulation and potentiates its intratumor accumulation. These properties represent the winning resource for this drug in that sustain its very favourable toxicity profile and the safe combination with other drugs. PLD has already been approved for treatment of advanced ovarian cancer patients failing first line platinum-based treatment. Moreover, Phase III trials have been completed, which will hopefully will bring PLD to front-line treatment, and in salvage setting in combination with platinum agents. This concise review will focus on the clinical role of PLD in the management of patients with epithelial OvCa.

What is the optimal approach to the administration of intraperitoneal chemotherapy in ovarian cancer?

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 36-39 ◽  
Author(s):  
M. Markman
Keyword(s):  
Ovarian Cancer ◽  
Intraperitoneal Chemotherapy ◽  
Clinical Setting ◽  
Small Volume ◽  
Intraperitoneal Administration ◽  
Advanced Ovarian Cancer ◽  
Primary Treatment ◽  
Evidence Based ◽  
Phase 3 ◽  
Optimal Approach

Three well-designed and conducted randomized phase 3 trials have revealed that the intraperitoneal administration of cisplatin-based chemotherapy as primary treatment of small-volume residual advanced ovarian cancer improves both progression-free and overall survivals compared to an all intravenous cisplatin-based regimen. Based on very reasonable extrapolations from existing evidence-based data, a number of possible “options” can be proposed that use the intraperitoneal route for delivery of chemotherapy in this clinical setting

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