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Strategies for Treatment of Relapsed Ovarian Cancer PowerPoint Presentation

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On : Feb 24, 2014

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  • Slide 1 - Randomized Phase III Trials of Intravenous vs. Intraperitoneal Therapy in Optimal Ovarian Cancer Deborah K. Armstrong, M.D. Associate Professor of Oncology, Gynecology and Obstetrics
  • Slide 2 - Development of Intraperitoneal Chemotherapy 1950’s: First use of intraperitoneal chemotherapy for malignant ascites 1968: Long-term peritoneal access device 1978: Demonstration of slow peritoneal clearance of some drugs 1984: Feasibility of intermittent large volume intraperitoneal therapy 1996: First report of a survival benefit for IP vs. IV chemotherapy in advanced ovarian cancer
  • Slide 3 - Peritoneal: Plasma Ratio Drug Peak AUC Cisplatin 20 12 Carboplatin --- 18 Melphalan 93 65 Adriamycin 474 --- 5-FU 298 367 MTX 92 100 Paclitaxel --- 1,000
  • Slide 4 - Intraperitoneal Therapy: Ovarian Cancer Rationale: Major route of spread within the peritoneal cavity Ability to reduce tumor volume with debulking Residual peritoneal tumor exposed to increased concentration of drug for prolonged period of time Limitations: Poor tumor penetration of bulk disease Less exposure of extra-peritoneal disease to drug Complications: Obstruction to flow or inadequate distribution Infection: peritonitis, abdominal wall or catheter Intestinal perforation
  • Slide 5 - GOG #104 SWOG #8501 Ovarian cancer Stage III Stratify: < 0.5 cm > 0.5-2 cm R A N D O M I Z E Cisplatin 100 mg/m2 IV Cyclophosphamide 600 mg/m2 IV q 21 days x 6 Cisplatin 100 mg/m2 IP Cyclophosphamide 600 mg/m2 IV q 21 days x 6 Second look Laparotomy
  • Slide 6 - GOG #104 Alberts et.al. NEJM Dec 1996 p=.02
  • Slide 7 - Consensus: GOG 104 The benefits of IP chemotherapy seen in GOG 104 are not greater than the benefits of the new agent, paclitaxel
  • Slide 8 - GOG #114 Ovarian cancer Stage III < 1.0 cm R A N D O M I Z E Cisplatin 75 mg/m2 IV Paclitaxel 135 mg/m2 IV q 21 days x 6 Carboplatin AUC=9 x 2 IV then Cisplatin 100 mg/m2 IP Paclitaxel 135 mg/m2 IV q 21 days x 6 Second look Laparotomy Cisplatin 75 mg/m2 IV Cyclophosphamide 750mg/m2 IV q 21 days x 6
  • Slide 9 - GOG #114 Ovarian cancer Stage III < 1.0 cm R A N D O M I Z E Cisplatin 75 mg/m2 IV Paclitaxel 135 mg/m2 IV q 21 days x 6 Carboplatin AUC=9 x 2 IV then Cisplatin 100 mg/m2 IP Paclitaxel 135 mg/m2 IV q 21 days x 6 Second look Laparotomy Cisplatin 75 mg/m2 IV Cyclophosphamide 750mg/m2 IV q 21 days x 6 X
  • Slide 10 - GOG #114 Markman et.el. JCO Feb 2001
  • Slide 11 - Consensus: GOG 114 The benefits of IP in GOG 114 are likely explained by the use of eight cycles of chemotherapy, not the use if IP administration (see GOG 182)
  • Slide 12 - GOG #172 Armstrong et.al. Abs #803, ASCO 2002 Ovarian cancer Optimal (<1cm) Stage III Stratify: Gross residual Planned 2nd look R A N D O M I Z E BRCA Analysis DNA Banking Paclitaxel 135 mg/m2/24h Cisplatin 75 mg/m2 q 21 days x 6 Paclitaxel 135 mg/m2/24h Cisplatin 100 mg/m2 IP D2 Paclitaxel 60 mg/m2 IP D8 q 21 days x 6 Second look Laparotomy (if chosen)
  • Slide 13 - Treatment Regimens Every 21 days x 6 Regimen 1 Intravenous Regimen 2 Intraperitoneal D1: IV Paclitaxel (135mg/m2/24h) D2: IV Cisplatin (75mg/m2) D1: IV Paclitaxel (135mg/m2/24h) D2: IP Cisplatin (100mg/m2) D8: IP Paclitaxel (60mg/m2) D1 IV D2 IV D1 IV D2 IP D8 IP
  • Slide 14 - GOG #172: Non-hematologic toxicities Armstrong et.al. Abs #803, ASCO 2002
  • Slide 15 - GOG #172: Hematologic Toxicities Armstrong et.al. Abs #803, ASCO 2002
  • Slide 16 - Courses of Protocol Therapy by Regimen * Carboplatin substituted for cisplatin
  • Slide 17 - GOG #172: Second Look Results
  • Slide 18 - GOG #172: Survival
  • Slide 19 - Relative Risk: IP vs. IV Therapy, GOG #172
  • Slide 20 - Figure 1
  • Slide 21 - Figure 2
  • Slide 22 - Modulating Toxicity of IP Therapy New approaches to improve toxicity profile Type of catheter used Timing of catheter placement Timing of chemotherapy relative to surgery relative to catheter placement Agents used Successful use of IP therapy requires: Training Skill Experience Dedication
  • Slide 23 - Consensus: 2005 The toxicities, inconvenience and cost of IP therapy are justified by the improved survival seen with this treatment New, targeted therapies are likely to be more effective in patients who have an excellent response to chemotherapy While we work to improve the tolerability and toxicities of IP therapy, it remains the most effective means of treating ovarian cancer today
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