GOG0172: The Dings • The recommended regimen is not feasible – Substitution of carboplatin for cisplatin – Reduce cisplatin from 100 mg/m 2 to 75 mg/m 2 – Change paclitaxel infusion and/or schedule – Need for 6 cycles not established • Role of intraperitoneal delivery not established – Trial design flawed (too many variables) – Dose-intensity hypothesis not validated – Potential role of biology, angiogenesis, microenvironment • This should not be our research priority
GOG0172: The Dings. The recommended regimen is not feasible Substitution of carboplatin for cisplatin Reduce cisplatin from 100 mg/m 2 to 75 mg/m 2 Change paclitaxel infusion and/or schedule Need for 6 cycles not established Role of intraperitoneal delivery not established - PowerPoint PPT Presentation
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GOG0172: The DingsGOG0172: The Dings
• The recommended regimen is not feasible– Substitution of carboplatin for cisplatin
– Reduce cisplatin from 100 mg/m2 to 75 mg/m2
– Change paclitaxel infusion and/or schedule
– Need for 6 cycles not established
• Role of intraperitoneal delivery not established– Trial design flawed (too many variables)
– Dose-intensity hypothesis not validated
– Potential role of biology, angiogenesis, microenvironment
• This should not be our research priority
• The recommended regimen is not feasible– Substitution of carboplatin for cisplatin
– Reduce cisplatin from 100 mg/m2 to 75 mg/m2
– Change paclitaxel infusion and/or schedule
– Need for 6 cycles not established
• Role of intraperitoneal delivery not established– Trial design flawed (too many variables)
– Dose-intensity hypothesis not validated
– Potential role of biology, angiogenesis, microenvironment
• This should not be our research priority
• Epithelial Ovarian CancerEpithelial Ovarian Cancer• Stage IC/II any gradeStage IC/II any grade• Stage IA/B high gradeStage IA/B high grade• No prior therapyNo prior therapy
• Only 70% met eligibility criteria (133 excluded)Only 70% met eligibility criteria (133 excluded)• 107/457 (23%) were incompletely staged107/457 (23%) were incompletely staged• Hematologic toxicity and neuropathy increased with 6 cyclesHematologic toxicity and neuropathy increased with 6 cycles
Bell JG, et al. Bell JG, et al. Gynecol OncolGynecol Oncol 102:432-9, 2006 102:432-9, 2006
Cisplatin 100 mg/mCisplatin 100 mg/m22 IP d1 IP d1Paclitaxel 135 mg/mPaclitaxel 135 mg/m22 (24 h) IV d1 (24 h) IV d1Paclitaxel 60 mg/mPaclitaxel 60 mg/m22 IP d8 IP d8
• Unique Biology of the Müllerian Epithelium and Peritoneal Cavity– Specialized relationship; spread via implantation– Frequent production of ascites, associated with VEGF– Negative immunoregulation (VEGF, IL-10, IL-6, IL-12, APC)
• Growth Factor Receptors– EGF-R frequently expressed, mutations uncommon, frequency of
gene amplification uncommon– ER/PR/AR frequently expressed, variable functionality– Other receptors less well characterized
• Growth Factor Production– Frequent high-level expression of VEGF– Increased expression of IL10, IL6, TNF, TGFα
• Unique Biology of the Müllerian Epithelium and Peritoneal Cavity– Specialized relationship; spread via implantation– Frequent production of ascites, associated with VEGF– Negative immunoregulation (VEGF, IL-10, IL-6, IL-12, APC)
• Growth Factor Receptors– EGF-R frequently expressed, mutations uncommon, frequency of
Burger et al., Burger et al., Proc Ann Meet ASCOProc Ann Meet ASCO 24:A5009 24:A5009
• Overall response rate 12/62 (19.4%), including 3 CROverall response rate 12/62 (19.4%), including 3 CR• 42% of pts alive and free of progression at 6 m42% of pts alive and free of progression at 6 m• Median number of cycles = 7, range = 1 to 29Median number of cycles = 7, range = 1 to 29
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GOG0170D: Bevacizumab Phase IIGOG0170D: Bevacizumab Phase II
Burger et al., Burger et al., Proc Ann Meet ASCOProc Ann Meet ASCO 24:A5009 24:A5009
GOG0126 Series (n = 220)GOG0126 Series (n = 220)Platinum-Resistant DiseasePlatinum-Resistant DiseasePFS @ 6 m = 0.16 (PFS @ 6 m = 0.16 (SE 0.025)SE 0.025)
GOG0170-D (n = 62)GOG0170-D (n = 62)PFS @ 6 m = 0.42PFS @ 6 m = 0.42