Intraperitoneal vs Intravenous Chemotherapy Following Neoadjuvant Chemotherapy in Ovarian Cancer

Inclusion Criteria

• •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