Paclitaxel i.v. Plus Cisplatin i.p for NACT in Patients With Advanced Ovarian Cancer

To test the effect of intravenous paclitaxel plus intraperitoneal cisplatin for neo-adjuvant chemotherapy in patients with advanced ovarian cancer, the investigators conducted a phase III single arm clinical trial. Included patients will receive interval debulking surgery after 2-6 cycles neoadjuvant chemotherapy based on the clinical judgment of the gynecologic oncologist. Six cycles of chemotherapy will conducted after surgery. And the neoadjuvant chemotherapy is as follows: paclitaxel 135 mg/m2 i.v. and cisplatin 75 mg/m2 i.p. on day 1. The primary end point is optimal debulking rates. the investigators also will evaluate effect on parameters of volume of ascites, tumor size, duration of surgery, hemorrhage, hospitalizations and postoperative complication etc. After comparing with data published online, the investigators will try to find out if paclitaxel i.v. plus cisplatin i.p. is a superior neoadjuvant chemotherapy for advanced ovarian carcinoma.

Sex

Female

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

1. Preferentially biopsy proven Stage IIIc or IV epithelial ovarian carcinoma, or peritoneal or fallopian tube carcinoma (the presence of metastases outside the pelvis measuring at least 2 cm in diameter (as noted during diagnostic laparoscopy or laparotomy or on computed tomography \[CT\]),with a low likelihood of achieving cytoreduction to, 1 cm (ideally to no visible disease). Or women who have a high perioperative risk profile.
2. Fine needle aspiration (FNA) showing an adenocarcinoma and cytopathology from ascites or pleural effusion is acceptable under the following conditions:

   the patient has a pelvic (ovarian) mass, AND omental cake or other metastasis larger than 2 cm in the upper abdomen and/or regional lymphnode metastasis irrespective of size or stage IV AND serum CA125/CEA ratio \> 25. If the serum CA125/CEA ratio is \< 25, a barium enema (or colonoscopy) and gastroscopy (or radiological examination of the stomach) should be negative for the presence of a primary tumor (\< 6 weeks before randomization), and normal mammography (\< 6 weeks).
3. WHO performance status of 0, 1, or 2.
4. No other serious disabling diseases contraindicating for cytoreductive surgery or platin based chemotherapy.
5. No other prior primary malignancies, except for carcinoma in situ of the cervix and basal carcinoma of the skin.
6. No clinical evidence of brain or leptomeningeal metastases.
7. Adequate hematological, renal and hepatic function to permit platin-paclitaxel based chemotherapy: WBC \> 3.0 x 109/L, N \>1.5 x 109/L, platelets \> 100 x 109/L, serum creatinine \< 1.25 x upper normal range, serum bilirubin \< 1.25 x upper normal range.
8. Absence of any psychological, familial, sociological or geographical condition potentially preventing compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before registration in the trial.
9. Before patient registration/randomization, informed consent must be obtained and documented according to national and local regulatory requirements and the local rules followed in the institution.

Exclusion Criteria:

1. serious disabling diseases that would contraindicate primary cytoreductive surgery or platinumbased chemotherapy
2. mucinous or borderline histology, extensive intra-abdominal adhesions, bowel obstruction or unresolved\>grade 2 peripheral neuropathy.

• BACKGROUNDRose PG, Nerenstone S, Brady MF, Clarke-Pearson D, Olt G, Rubin SC, Moore DH, Small JM; Gynecologic Oncology Group. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. 2004 Dec 9;351(24):2489-97. doi: 10.1056/NEJMoa041125. PMID 15590951
• BACKGROUNDKehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, Luesley D, Perren T, Bannoo S, Mascarenhas M, Dobbs S, Essapen S, Twigg J, Herod J, McCluggage G, Parmar M, Swart AM. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet. 2015 Jul 18;386(9990):249-57. doi: 10.1016/S0140-6736(14)62223-6. Epub 2015 May 19. PMID 26002111
• BACKGROUNDVergote I, Trope CG, Amant F, Kristensen GB, Ehlen T, Johnson N, Verheijen RH, van der Burg ME, Lacave AJ, Panici PB, Kenter GG, Casado A, Mendiola C, Coens C, Verleye L, Stuart GC, Pecorelli S, Reed NS; European Organization for Research and Treatment of Cancer-Gynaecological Cancer Group; NCIC Clinical Trials Group. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med. 2010 Sep 2;363(10):943-53. doi: 10.1056/NEJMoa0908806. PMID 20818904
• BACKGROUNDWright AA, Bohlke K, Armstrong DK, Bookman MA, Cliby WA, Coleman RL, Dizon DS, Kash JJ, Meyer LA, Moore KN, Olawaiye AB, Oldham J, Salani R, Sparacio D, Tew WP, Vergote I, Edelson MI. Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Oct 1;34(28):3460-73. doi: 10.1200/JCO.2016.68.6907. Epub 2016 Aug 8. PMID 27502591
• BACKGROUNDLopez JA, Krikorian JG, Reich SD, Smyth RD, Lee FH, Issell BF. Clinical pharmacology of intraperitoneal cisplatin. Gynecol Oncol. 1985 Jan;20(1):1-9. doi: 10.1016/0090-8258(85)90118-0. PMID 4038390
• BACKGROUNDDedrick RL, Myers CE, Bungay PM, DeVita VT Jr. Pharmacokinetic rationale for peritoneal drug administration in the treatment of ovarian cancer. Cancer Treat Rep. 1978 Jan;62(1):1-11.