Factors associated with improved toxicity and tolerability of intraperitoneal chemotherapy in advanced-stage epithelial ovarian cancers

Teefey, Patrick; Zgheib, Nadim Bou; Apte, Sachin M.; Bosquet, Jesús González; Judson, Patricia L.; Roberts, William S.; Lancaster, Johnathan M.

doi:10.1016/j.ajog.2013.03.012

Cited by 15 publications

(13 citation statements)

References 11 publications

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“…Moreover, in human studies intraperitoneal delivery has at least the same response rate as the intravenous route and therefore are used more and more in clinical practice [26]. To determine the maximum tolerable dosage (MTD) of carboplatin (Teva, Helsingborg, Sweden 10 mg/ml) and paclitaxel (Fresenius Kabi, Halden, Norway 6 mg/ml), the following different dosages were evaluated.…”

Section: Methodsmentioning

confidence: 99%

First In-Mouse Development and Application of a Surgically Relevant Xenograft Model of Ovarian Carcinoma

Helland

Popa²,

Vintermyr

et al. 2014

PLoS ONE

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PurposePreclinical models of epithelial ovarian cancer have not been exploited to evaluate the clinical standard combination therapy of surgical debulking with follow-up chemotherapy. As surgery is critical to patient survival, here we establish a combined surgical/chemotherapy xenograft model of epithelial ovarian cancer and demonstrate its translational relevance.Experimental DesignSKOV-3luc+ ovary cancer cells were injected topically into the ovaries of immunodeficient mice. Disease development and effect of clinical standard treatment including hysterectomy, bilateral salpingoophorectomy and removal of metastasis with follow up chemotherapy (carboplatin 12 mg/kg + paclitaxel 15 mg/kg) was evaluated by clinical parameters. Tumor burden was quantified by bioluminescence imaging (BLI).ResultsThe xenograft ovarian tumors developed were poorly differentiated and multicystic and the disease disseminated into the peritoneal cavity. When compared to the controls with a mean survival time of 4.9 weeks, mice treated with surgery and chemotherapy, surgery or chemotherapy demonstrated significantly improved mean survival of 16.1 weeks (p = 0.0008), 12.7 weeks (p = 0.0008), or 10.4 weeks (p = 0.008), respectively.ConclusionCombined surgical intervention and adjuvant chemotherapy was demonstrated for the first time in an orthotopic xenograft model of ovarian cancer. Similar to observation in human studies the combined approach resulted in the longest medial survival time, advocating application of this strategy in future preclinical therapeutic development for this disease.

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Section: Methodsmentioning

confidence: 99%

First In-Mouse Development and Application of a Surgically Relevant Xenograft Model of Ovarian Carcinoma

Helland

Popa²,

Vintermyr

et al. 2014

PLoS ONE

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“…Although the three GOG protocols assessing IP chemotherapy only evaluated patients with stage III disease [6-8], several institutions consider that the benefits of IV/IP chemotherapy should be extended to select women with optimally cytoreduced stage IV epithelial ovarian cancer. Indeed, recent publications reporting on IV/IP therapy have included these patients [16,17]. With regards to stage IV patients at our institution, IV/IP therapy is sometimes considered for those who are optimally debulked and who had resected pleural disease, supradiaphragmatic lymph nodes, isolated liver or cutaneous metastasis, or a malignant pleural effusion, with no remaining signs of extraperitoneal disease postoperatively.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of the Number of Postoperative Intraperitoneal Chemotherapy Cycles for Patients With Advanced Epithelial Ovarian Cancer

Suidan¹,

Zhou

Iasonos

et al. 2015

International Journal of Gynecological Cancer

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Objective Phase III trials have demonstrated a survival advantage for patients with optimally debulked epithelial ovarian cancer (EOC) who received intravenous (IV) and intraperitoneal (IP) chemotherapy compared to IV therapy alone. This was despite a significant proportion of patients in the IV/IP arms not completing all six planned cycles. Our objective was to evaluate the prognostic significance of the number of IV/IP cycles administered. Methods/materials Data were analyzed for all patients with stage III-IV EOC who underwent optimal primary cytoreduction followed by ≥1 cycle of IV/IP chemotherapy from 1/2005 to 7/2011 at our institution. A landmark analysis was performed to associate progression-free (PFS) and overall survival (OS) with the number of IV/IP cycles given. Results We identified 201 patients; 26 (13%) received 1-2 cycles of IV/IP chemotherapy, 41 (20%) received 3-4 cycles, and 134 (67%) received 5-6 cycles. Five-year PFS for patients who received 1-2, 3-4, and 5-6 cycles was 18%, 29%, and 17%, respectively. Five-year OS for patients who received 1-2, 3-4, and 5-6 cycles was 44%, 54%, and 57%, respectively. There was no significant difference in PFS (P=0.31) or OS (P=0.14) between the three groups. The most common reason for discontinuing IV/IP therapy was treatment-related toxicity (77%). Postoperative complications were the most common reason for not initiating IV/IP therapy (42%) in patients who subsequently transitioned to it. Conclusions We did not detect a significant survival difference between patients who received 1-2, 3-4, or 5-6 IV/IP chemotherapy cycles. Women may still derive a survival benefit if they receive <6 IV/IP cycles.

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“…Although the three GOG protocols assessing IP chemotherapy only evaluated patients with stage III disease [6][7][8], several institutions consider that the benefits of IV/IP chemotherapy should be extended to select women with optimally cytoreduced stage IV epithelial ovarian cancer. Indeed, recent publications reporting on IV/IP therapy have included these patients [16,17]. With regards to stage IV patients at our institution, IV/IP therapy is sometimes considered for those who are optimally debulked and who had resected pleural disease, supradiaphragmatic lymph nodes, isolated liver or cutaneous metastasis, or a malignant pleural effusion, with no remaining signs of extraperitoneal disease postoperatively.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of the number of postoperative intraperitoneal chemotherapy cycles for patients with advanced epithelial ovarian cancer

Suidan¹,

Zhou²,

Iasonos³

et al. 2014

Gynecologic Oncology

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Factors associated with improved toxicity and tolerability of intraperitoneal chemotherapy in advanced-stage epithelial ovarian cancers

Cited by 15 publications

References 11 publications

First In-Mouse Development and Application of a Surgically Relevant Xenograft Model of Ovarian Carcinoma

First In-Mouse Development and Application of a Surgically Relevant Xenograft Model of Ovarian Carcinoma

Prognostic Significance of the Number of Postoperative Intraperitoneal Chemotherapy Cycles for Patients With Advanced Epithelial Ovarian Cancer

Prognostic significance of the number of postoperative intraperitoneal chemotherapy cycles for patients with advanced epithelial ovarian cancer

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