1. Gynecologic Malignancies Dr. David Edelmann Sharett Institute of Oncology Hadassah Medical Organization

2. Cervical cancer Eudometrial cancer Ovarian cancer 13500 (55000 C.I.S) 3100022000No. new cases/ year 4400570013300No. deaths/ year U.S.A. Data (1993)

3. 5 Year Survival Cervical Ca 67% Eudometrial Ca 67% Ovarian Ca 30%All stages 85%75%90% Stage I 55%58%(orIIIA)35% Stage II 30% (IIIB only)20% Stage III 0-15%10%(IIIC or IV) 5-10% Stage IV

4. Most Gynecologic Malignancies are Highly CT and RT Responsive

5. Ovarian Cancer (O.C.) Epithelial O.C. – 90% (85% Invasive 15% Borderline) Non-epithelial – 10% Germ cell tumor Sex-cord stromal tumor

6. Treatment A. Surgery is the standard first step modality. It includes: 1. Surgical staging 2. Cytoreductive (debulking) surgery. An attempt for optimal debulking (removal of all tumor nodules > 1cm).

7. Rationale: 5 year survival according to residual tumor at the end of cytoreductive surgery. a. Microscopic dis. Only - 50-75% b. Optimal dis. - 30-40% c. Suboptimal dis. - 5%

8. A trend for a new approach – Neoadj. CT or interventional debulking surgery followed by further CT. EORTC randomized trial.

9. B. Postoperative treatment: (Epithelial O.C.) 1. Early stage (I-II) a. IA-IB (G1)-F.U. only; G2- controversial. b. All other – Several options:

10. I. Whole abdomen and pelvis irradiation (optimal debulking). Entire peritoneal cavity 2000-3000 cGy (100-125cGy fractions) with boost to the pelvis to a total dose of 5000 cGy (180 cGy fractions).

11. Disadvantage: substantial morbidity – 15-40% with severe myelsuppression: diarrhea – 78% bowel obstruction – 14% fistulae retroperitoneal fibrosis, proctitis, enteritis, cystitis, hepatitis, nephritis.

12. II. I.P. radiocolloids ( 32 P) identical results with 5ys – 80% III.CT with melphalan which cause ANLL after 12 cycles in 10% of the pts.

13. IV.Combination CT – plat. Based – CPx4-6 More effective and less leukemogenic then melphalan.

14. 2. Advanced stage (III-IV) Standard postop. CT: A plat. compound with an A.A.: Cisplatin =>75mg/m 2 / cycleequally oreffective Carboplatin=> 350mg/m 2 /cycle with cyclophosphamide CT is delivered on day 1 every 3-4 weeks for 6 cycles.

15. R.R. can be assessed more precisely in pts. with a suboptimally debulked tumor. Response and outcome in pts. with advanced (optimal + suboptimal ) O.C. following plat.- based comb. CT: R.R.-60-80% cCR-30-60% pCR-10-30% Median survival-20-30 mo

16. The new standard CT for subopt. Stage IIIC and stage IV dis. NEJ Med. 334(1): 1-6, 1996 (GOG) phase III TP vs. CP- 386 pts 216 with measurable dis. Median survival (m) Median PFI (m) pCRcCRR.R. 241320%31%60%CP 381826%51%73%TP <0.001 0.080.01 P CCC (37) 96% 77% 27% 25