Intraperitoneal vs Intravenous Chemotherapy Following Neoadjuvant Chemotherapy in Ovarian Cancer

DISEASE CHARACTERISTICS:

Histologically confirmed ovarian epithelial, primary serous type peritoneal, or fallopian tube carcinoma

Patients with ovarian cancer of the clear cell histology are eligible. Histologic confirmation is preferably by biopsy or limited excision prior to neo-adjuvant treatment. If the diagnosis prior to neo-adjuvant chemotherapy is based on cytology, histologic confirmation is required prior to randomization. Histologic confirmation can be obtained at the time of debulking surgery by intra-operative frozen section, thus permitting intra-operative randomization, or by final pathologic review of the resected specimen if randomization is to be performed following debulking surgery.

Initial FIGO stage IIB-III disease

Stage IV disease allowed provided the only criterion for stage IV disease is the presence of a pleural effusion confirmed to be associated with positive cytology for ovarian cancer
Completed ≥ 3 but no more than 4 courses of platinum-based neoadjuvant chemotherapy prior to the first debulking surgery

Meets the following criteria for surgical treatment prior to randomization:

Initial Diagnosis: No debulking surgery was attempted or completed.
The patient's first cytoreductive (debulking) surgery must be after neoadjuvant chemotherapy (Delayed Primary Debulking). The delayed primary debulking surgery must be completed no more than 4 weeks after commencing administering of the last cycle of neoadjuvant chemotherapy and must be completed no more than 6 weeks prior to randomization.

Surgery will include total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and any additional procedures required to achieve maximal cytoreduction with residual disease of 1 cm or less as assessed by the surgeon at the end of surgery.

Delayed primary debulking surgery must be completed no more than 4 weeks after the last course of neoadjuvant chemotherapy and must be completed no more than 6 weeks prior to randomization
Surgery will include total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and any additional procedures required to achieve maximal cytoreduction with residual disease of ≤ 1 cm as assessed by the surgeon at the end of surgery
No borderline ovarian tumors (i.e., tumors of low malignant potential) alone
No mucinous tumor

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 12 weeks
Granulocyte count ≥ 1.5 x 10^9/L
Platelet count ≥ 100 x 10^9/L
Serum creatinine ≤ upper limit of normal (ULN) OR > ULN to ≤ 1.25 ULN provided measured creatinine clearance is > 60 mL/min
Serum bilirubin normal
AST/ALT ≤ 2.5 times ULN
Fertile patients must use effective contraception
Able (i.e., sufficiently fluent) and willing to complete the quality of life questionnaires
Accessible for treatment and follow-up
No history of other malignancy, except adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years

No uncontrolled atrial or ventricular arrhythmias including second or third degree heart block unless managed with implanted pacemaker

Patients with a history of first degree heart block are eligible
No documented myocardial infarction within the past 6 months preceding randomization (pretreatment ECG evidence only of infarct will not exclude patients)
No diagnosis of bowel obstruction

No serious illness or medical condition which would not permit the patient to be managed according to protocol including, but not limited to, any of the following:

Prior allergic reactions to drugs containing cremophor or to compounds chemically related to cisplatin, paclitaxel, or carboplatin
Symptomatic congestive heart failure within the past 6 months or other conditions which would lead to a contraindication of a high-volume saline diuresis
History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent
Active uncontrolled infection
Persistent peripheral neuropathy or hearing loss ≥ grade 2 resulting from prior therapy
Extensive intraperitoneal adhesion intra- or post-operatively which would impede intraperitoneal treatment delivery

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior therapy for ovarian cancer, except for neoadjuvant platinum-based chemotherapy and surgery
No concurrent intraperitoneal adhesion barriers
No other concurrent anticancer treatment, including cytotoxic agents, biological response modifiers, immunotherapy, anticancer hormone therapy, or investigational drug therapy
No other concurrent experimental drugs or anticancer therapy