Management of Recurrent Ovarian Carcinoma Lee-may Chen, M.D. Department of Obstetrics, Gynecology, & Reproductive Sciences UCSF Comprehensive Cancer Center Ovarian Cancer Survival United States, 28: 1 9 8 7 6 5 4 3 2 1 Diagnosis Stage I FIGO, 1998 Stage II Stage III Stage IV 21,65 new diagnoses 15,52 cancer deaths 1 9 8 7 6 5 4 3 2 1 Stage I Stage II 5-year Survival Stage III Stage IV 1983-87 1988-94 SEER, 1999 Ovarian Cancer Treatment Ovarian Cancer Follow-up Primary Staging/Cytoreductive Surgery then Platinum-Taxane chemotherapy Early disease: 3-6 cycles of chemotherapy Advanced disease or medical comorbidities: consider primary chemotherapy and interval cytoreductive surgery ROS / Pelvic exam CA125 blood test Imaging studies Questions: Intraperitoneal chemo, dose dense chemo, bevacizumab, maintenance therapy 1
Goals in Recurrent Ovarian CA Disease Free Interval Survival Durable response Minimal toxicities Symptom control Quality of life Time from Primary Chemotherapy -3 mo: Refractory 3-6 mo: Resistant 6-24 mo: Sensitive > 24 mo: Very Sensitive 6 12 18 24 3 Months Approaches to Recurrent Ovarian CA Secondary Cytoreduction vs. Chemotherapy Retreatment with Carboplatin &/or Taxol Other second line chemotherapy agents Radiation therapy Investigational agents Supportive care, symptom management Secondary Cytoreduction Favorable selection criteria Good performance status Optimally debulked at primary surgery Chemo-sensitive tumor Disease-free interval greater than 12 months Macronodular tumor distribution Absence of mesenteric disease Absence of ascites 2
Secondary Cytoreduction Meta-analysis of 219 patients, 1983-27 Median disease-free interval 2.2 mo. Mean proportion of complete cytoreduction 52.2% Median progression-free survival 3.3mo. Improved cytoreduction associated improved survival Bristow et al, Gyncol Oncol, 29 Second-line Chemotherapy Carboplatin Topotecan Cisplatin Gemcitabine Paclitaxel Docetaxel Liposomal Doxorubicin Vinorelbine Ifosfamide Hexamethylmelamine Etoposide Tamoxifen Bevacizumab Olaparib Investigational agents Retreatment with Platinum Second Line Chemotherapy 14 Trials, 198-1997 Response Rate n=82 1 9 8 7 6 5 4 3 2 1 59% 33% 27% 12% < 5 mo 5-12 mo 12-24 mo > 24 mo Treatment-free Interval 14 12 1 8 Months 6 4 2 PFI Survival Markman, J Clin Oncol, 1991 Carbo Gemcitabine Paclitaxel Tamoxifen Topotecan Knopf, ASCO 1998 3
Radiation therapy Palliative Radiation in Advanced Disease Second line therapy Best with small volume disease (microscopic) GI morbidity Palliative treatment--for bleeding or pain n=33, Fox Chase, 1987-1993 79% response rate, median duration 4 mo. 85-9% control of rectal or vaginal bleeding 83% relief of pain Corn et al, Cancer, 1994 n=8, 1983-1988, advanced or recurrent ovarian CA Median age 67 (range 26-9) Median 6 cycles of prior chemo (-2) Palliative treatment pain, mass, obstruction, positive second look, ascites, vaginal bleeding, rectal bleeding, lymphedema, skin involvement, brain metastases Overall 73% response rate, median duration 9mo. Tinger et al, Int J Radiat Oncol Biol Phys, 21 Palliative Radiation in Rectovaginal Disease n=28, recurrent ovarian cancer with vaginal &/or perirectal disease 79% with prior surgery, chemotherapy 68% treated with external beam only, 7% with brachytherapy only, 18% with both 79% response rate, vaginal bleeding controlled in all patients, median survival > 2years Clear cell ovarian CA and Radiation Case report 58yo woman with progressive Stage IC clear cell ovarian carcinoma after primary surgery, paclitaxel & carboplatin, then irinotecan chemotherapy 7cm pelvic recurrence involving vagina, rectal wall 5cGy external beam radiation to whole pelvis in 25 fractions Rectovaginal fistula but NED @ 1 ½ years Firat & Erickson Gynecol Oncol, 21 Takai et al, Arch Gynecol Obstet, 22 4
Ovarian CA as a Chronic Disease Goal of curative intent vs. Goal of disease stabilization, palliation for long-term survival Partial response and Stable disease still provides some survival advantage Limited by chemotherapy toxicities on Quality of Life 5