Intraperitoneal versus Intravenous Cisplatin in Combination with Intravenous Cyclophosphamide and Epidoxorubicin in Optimally Cytoreduced Advanced Epithelial Ovarian Cancer: A Randomized Trial of the Gruppo Oncologico Nord-Ovest

Gadducci, Angiolo; Carnino, F; Chiara, Silvana; Brunetti, I.; Tanganelli, L; Romanini, Antonella; Bruzzone, M; Conte, Pierfranco

doi:10.1006/gyno.1999.5677

Cited by 124 publications

(116 citation statements)

References 17 publications

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“…7,8,25 As mentioned, IP Pt-based therapy provides high locoregional concentrations of the drug and longer exposure in the peritoneal cavity as compared with the intravenous route. 5 Yet, the high local drug concentration would potentially give rise to higher risk of toxicities.…”

Section: Discussionmentioning

confidence: 99%

Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft

Chaudhury¹,

Das²,

Bunte³

et al. 2012

IJN

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Intraperitoneal (IP) therapy with platinum (Pt)-based drugs has shown promising results clinically; however, high locoregional concentration of the drug could lead to adverse side effects. In this study, IP administration was coupled with a folate receptor-targeted (FRT) liposomal system, in an attempt to achieve intracellular delivery of the Pt-based drug carboplatin in order to increase therapeutic efficacy and to minimize toxicity. In vitro and in vivo activity of FRT carboplatin liposomes was compared with the activity of free drug and nontargeted (NT) carboplatin liposomes using FR-overexpressing IGROV-1 ovarian cancer cells as the model. Significant reduction in cell viability was observed with FRT liposomes, which, compared with the free drug, provided an approximately twofold increase in carboplatin potency. The increase in drug potency was correlated with significantly higher cellular accumulation of Pt resulting from FRT liposomal delivery. Further evaluation was conducted in mice bearing intraperitoneally inoculated IGROV-1 ovarian tumor xenografts. A superior survival rate (five out of six animals) was achieved in animals treated with FRT carboplatin liposomes, injected intraperitoneally with a dose of 15 mg/kg and following a schedule of twice-weekly administration for 3 weeks. In contrast, no survivors were observed in the free drug or NT carboplatin liposome groups. The presence of cancer cells in lung and liver tissues was observed in the saline, free carboplatin, and NT carboplatin liposome groups. However, there was no sign of cancer cells or drugrelated toxicity detected in tissues from the animals treated with FRT carboplatin liposomes. The results of this study have demonstrated for the first time that the approach of coupling IP administration with FRT liposomal delivery could provide significantly improved therapeutic efficacy of carboplatin in the treatment of metastatic ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft

Chaudhury¹,

Das²,

Bunte³

et al. 2012

IJN

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“…IP therapy has been under development for several decades and has shown survival benefits in selected patient groups (5,(16)(17)(18)(19)(20). Most studies, conducted in patients with ovarian or gastrointestinal cancer, used IP therapy preoperatively to downstage the disease to facilitate surgical debulking and intraoperatively and postoperatively to treat residual small and microscopic tumors (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36).…”

Section: Part I Peritoneal Cancer and Intraperitoneal Cancer Therapymentioning

confidence: 99%

Versatility of Particulate Carriers: Development of Pharmacodynamically Optimized Drug-Loaded Microparticles for Treatment of Peritoneal Cancer

Wientjes

2015

AAPS J

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Abstract. Intraperitoneal (IP) chemotherapy confers significant survival benefits in cancer patients. However, several problems, including local toxicity and ineffectiveness against bulky tumors, have prohibited it from becoming a standard-of-care. We have developed drug-loaded, tumor-penetrating microparticles (TPM) to address these problems. TPM comprises two components and uses the versatile PLGA or poly(lacticco-glycolic acid) copolymer to provide tumor-selective adherence and pharmacodynamically optimized fractionated dosing to achieve the desired tumor priming (which promotes particle penetration into tumors) plus immediate and sustained antitumor activity. Preclinical studies show that TPM is less toxic and more effective against several IP metastatic tumors with different characteristics (fast vs. slow growing, porous vs. densely packed structures, wide-spread vs. solitary tumors, early vs. late stage, with or without peritoneal carcinomatosis or ascites), compared to the intravenous paclitaxel/ Cremophor micellar solution that has been used off-label in previous IP studies. TPM further requires less frequent dosing. These encouraging preclinical results have motivated the follow-up clinical development of TPM. We are working with National Institutes of Health on the IND-enabling studies.

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“…The U.S. National Cancer Institute (nci) reviewed data from seven randomized trials comparing IV-IP with standard IV administration of chemotherapy in women who had undergone primary debulking surgery (Table i). On average, IP-IV chemotherapy was associated with a 21.6% decrease in risk of death (hazard ratio: 0.78; 95% confidence interval: 0.69 to 0.89) [5][6][7][8][9][10][11][12] . They concluded that IP-IV chemotherapy should be considered a standard of care for a select group of women with eoc.…”

Section: Intraperitoneal Chemotherapymentioning

confidence: 99%

“…The basis of the experimental arms in all the randomized IP clinical trials has been IP cisplatin [5][6][7][8][9][10][11][12] . However, that agent, delivered by that route, is associated with significant toxicity, particularly neuropathy and emesis.…”

Section: Rationale For the Study Armsmentioning

confidence: 99%

Phase II/III Study of Intraperitoneal Chemotherapy after Neoadjuvant Chemotherapy for Ovarian Cancer: NCIC CTG OV.21

et al. 2011

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Despite the efficacy of intravenous (IV) platinum and paclitaxel chemotherapy, more than 75% of patients with stage iii and iv eoc ultimately relapse and die of their disease 2 . IntraperItoneal ChemotherapyThe peritoneal cavity is the principle site of spread and recurrence in women with eoc. Intraperitoneal (IP) administration of chemotherapy, as a means of increasing the dose intensity delivered to the tumour while minimizing systemic toxicity, is therefore an attractive therapeutic approach 3 . Advantages of this administration route include high IP concentration and longer half-life of the drug in the peritoneal cavity than are observed with IV administration. For cisplatin, the most commonly used IP chemotherapeutic agent, IP administration translates into an exposure in the peritoneal cavity that is greater by a factor of 10-20 than is achievable with the IV route 4 . Publication of the Gynecologic Oncology Group (gog) 172 study, which demonstrated a significant overall survival benefit (17.4 months) for IP paclitaxel-IV cisplatin over conventional IV chemotherapy in women with stage iii eoc undergoing "upfront" optimal (≤1 cm) debulking surgery prompted a re-evaluation of IP chemotherapy 5 . The U.S. National Cancer Institute (nci) reviewed data from seven randomized trials comparing IV-IP with standard IV administration of chemotherapy in women who had undergone primary debulking surgery (Table i). On average, IP-IV chemotherapy was associated with a 21.6% decrease in risk of death (hazard ratio: 0.78; 95% confidence interval: 0.69 to 0.89) [5][6][7][8][9][10][11][12] . They concluded that IP-IV chemotherapy should be considered a standard of care for a select group of women with eoc.Despite the favourable outcomes, IP chemotherapy has not been universally adopted. In all seven studies, toxicity was higher in the experimental arm, particularly when considered in comparison with standard IV carboplatin and paclitaxel. Dropout rates were high, with completion rates ranging from 71% (gog 114) to 42% (gog 172). The optimal aBStraCt Three large randomized clinical trials have shown a survival benefit in women with stage iii epithelial ovarian cancer (eoc) who receive intraperitoneal (IP) chemotherapy after optimal primary debulking surgery. The most recent Gynecologic Oncology Group study, gog 172, showed an improvement in median overall survival of approximately 17 months. That result led to a U.S. National Cancer Institute (nci) clinical announcement recommending that IP chemotherapy be considered for this group of women with eoc. However, IP chemotherapy is associated with increased toxicity, and rates for completion of treatment are low (42% in gog 172). The optimal IP regimen and duration of treatment has yet to be defined. Women undergoing chemotherapy before optimal debulking surgery were not included in the studies or in the nci clinical announcement. The National Cancer Institute of Canada Clinical Trials Group has developed a protocol for a randomized phase ii/iii study which will examine whether I...

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Intraperitoneal versus Intravenous Cisplatin in Combination with Intravenous Cyclophosphamide and Epidoxorubicin in Optimally Cytoreduced Advanced Epithelial Ovarian Cancer: A Randomized Trial of the Gruppo Oncologico Nord-Ovest

Cited by 124 publications

References 17 publications

Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft

Potent therapeutic activity of folate receptor-targeted liposomal carboplatin in the localized treatment of intraperitoneally grown human ovarian tumor xenograft

Versatility of Particulate Carriers: Development of Pharmacodynamically Optimized Drug-Loaded Microparticles for Treatment of Peritoneal Cancer

Phase II/III Study of Intraperitoneal Chemotherapy after Neoadjuvant Chemotherapy for Ovarian Cancer: NCIC CTG OV.21

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