1. 台北榮民總醫院 婦產部 主治醫師 吳 華 席

2. Introduction Ovarian cancer –The lethal gynecologic cancer The major prognostic factors –Residual tumor at primary surgery –Sensitivity to platinum-based C/T In platinum-resistant cancers –None of drugs currently used showed superiority in phase II studies

3. RCTs for platinum-resistant ovarian cancer patients PLD vs Topotecan –Equivalent in TTP & OS –More hematologic toxicity & alopecia in Topotecan group –More PPE, stomatitis & mucosities in PLD group (Gordon, JCO, 19:3312, 2001) Gemzar vs PLD –PLD : 50 mg/m2 q4wks (by FDA)  PPE 23% –Higher mucositis /stomatitis than 40 mg/m2 q4wks (Mutch, JCO, 25:2811, 2007)

4. Ferrandina, G. et al. J Clin Oncol; 26:890-896 2008 Fig 1. Study design Gemcitabine 1000 mg/m2 on D1, D8 & D15 q4w Pegylated liposomal doxorubicin 40 mg/m2 q4w P/T only; recurrence/progression in 12 months

5. Patients Characteristics

6. Study Drug Administration Details

7. Toxicities

8. Clinical Responses Overall response: p=0.066 16 vs 29% L vs G Clinical benefit: p=0.085 58 vs 71%

9. Ferrandina, G. et al. J Clin Oncol; 26:890-896 2008 Fig 2. Kaplan-Meier estimate of (A) time to progression (TTP) and (B) overall survival (OS) curves In TTP, p= 0.411 In OS, p=0.048

10. Results The rate of response was lower in pts experiencing recurrence within 6 months versus pt with a PFI of 7-12 months (15% vs 31%, p=0.032) Progression of disease: 88% Died of disease: 62%

11. Ferrandina, G. et al. J Clin Oncol; 26:890-896 2008 Fig 3. Box-whiskers plots of the global quality of life (QoL) scores for patients treated with pegylated liposomal doxorubicin (PLD; n = 60 at baseline) and gemcitabine (GEM; n = 61 at baseline)

12. Discussion GEM is not superior to PLD in terms of TTP in Pt with recurrence either within 6 months or 7-12 months Although there was a trend for more favorable OS in the PLD arms, the relative low number of patients, the borderline statistical significance, and the scarcity of data on post-progression chemotherapy regimens do not allow any firm conclusion to be drawn.

13. Conclusion Gemcitabine –Does not provide an advantage compared to LPD –Could be considered in salvage setting LPD –Proved to be more manageable compared with GEM, because The schedule Negligible hematologic toxicity Low rate of mucositis and skin toxicity  favorable therapeutic index of LPD