RATIONALE: Drugs used in chemotherapy, such as paclitaxel, cisplatin, and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether paclitaxel is more effective when given together with cisplatin or topotecan with or without bevacizumab in treating patients with cervical cancer.

PURPOSE: This randomized phase III trial is studying the side effects of paclitaxel when given together with cisplatin or topotecan with or without bevacizumab and to compare how well they work in treating patients with stage IVB, recurrent, or persistent cervical cancer.

OBJECTIVES:

Primary

• To compare the overall survival of patients with stage IVB, recurrent, or persistent carcinoma of the cervix treated with paclitaxel in combination with cisplatin or topotecan with vs without bevacizumab.
• To compare the frequency and severity of adverse events associated with these regimens as assessed by NCI CTCAE v3.0.

Secondary

• To compare the progression-free survival of these patients.
• To compare the proportion of patients with tumor response.

Tertiary

• To compare the health-related quality of life as assessed by the FACT-Cx TOI; neuropathy symptoms as assessed by the FACT/GOG-Ntx4 subscale; and pain as assessed by the Brief Pain Inventory in these patients.
• To evaluate the impact of age, race, performance status, stage, histology, grade, disease site, prior chemoradiotherapy, and time to recurrence on response rate, progression-free survival, and overall survival of these patients.
• To determine the prevalence of active smoking in these patients.
• To estimate the extent of tobacco/nicotine dependence in these patients.
• To determine if smoking is an independent risk factor for progression-free survival and overall survival of these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to disease status (recurrent/persistent disease vs primary stage IVB disease), GOG performance status (0 vs 1), and prior platinum therapy as a radiosensitizer (yes vs no). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV on day 1 or 2.
• Arm II: Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV and bevacizumab IV over 30-90 minutes on day 1 or 2.
• Arm III: Patients receive paclitaxel IV over 3 hours on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.
• Arm IV: Patients receive paclitaxel IV over 3 hours and bevacizumab IV over 30-90 minutes on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.

In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients complete quality-of-life questionnaires, including the FACT-Cx TOI, FACT/GOG-Ntx4, and Brief Pain Inventory, at baseline, before courses 2 and 5, and at 6 and 9 months after course 1. Patients also complete a smoking questionnaire at baseline.

After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma of the cervix, including any of the following subtypes:
  • Squamous cell carcinoma
  • Adenosquamous cell carcinoma
  • Adenocarcinoma
• Primary stage IVB, recurrent, or persistent disease not amenable to curative treatment with surgery and/or radiotherapy
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
  • Biopsy confirmation required if target lesion(s) measures < 30 mm or if the treating physician determines it is clinically indicated
  • Has ≥ 1 "target lesion" that can be used to assess response
    • Tumors within a previously irradiated field are designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence ≥ 90 days following completion of radiotherapy
• No history or evidence of CNS disease, including primary brain tumor, brain metastases, or craniospinal metastases

PATIENT CHARACTERISTICS:

• GOG performance status 0-1
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 times normal
• SGOT ≤ 2.5 times normal
• Alkaline phosphatase ≤ 2.5 times normal
• PT/INR ≤ 1.5 (or in-range INR, if patient is on a stable dose of therapeutic warfarin for management of venous thrombosis, including pulmonary thromboembolus)
• PTT < 1.2 times upper limit of normal
• Serum creatinine normal OR creatinine clearance ≥ 60 mL/min
• Urine protein:creatinine ratio 1.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• No active infection requiring antibiotics
• No significant traumatic injury within the past 28 days
• No serious non-healing wound, ulcer, or bone fracture
  • Patients with granulating incisions healing by secondary intention are eligible provided there is no evidence of fascial dehiscence or infection AND the wound is examined weekly
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 3-6 months
  • Patients must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation
• No clinical symptoms or signs of gastrointestinal obstruction requiring parenteral hydration and/or nutrition
• No active bleeding or pathologic condition that carries a high risk of bleeding (e.g., known bleeding disorder, coagulopathy, or tumor involving major vessels)
• No seizures not controlled with standard medical therapy
• No cerebrovascular accident (i.e., stroke), transient ischemic attack, or subarachnoid hemorrhage within the past 6 months
• No clinically significant cardiovascular disease, including any of the following:
  • Uncontrolled hypertension, defined as systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg
  • Myocardial infarction or unstable angina within the past 6 months
  • NYHA class II-IV congestive heart failure
  • Serious cardiac arrhythmia requiring medication
    • Atrial fibrillation allowed provided it is asymptomatic and ventricular rate is controlled
  • Significant peripheral vascular disease (i.e., ≥ grade 2 peripheral vascular disease, as defined by NCI CTCAE v3.0 criteria)
• No bilateral hydronephrosis that cannot be alleviated by ureteral stents or percutaneous drainage
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
• No other invasive malignancy within the past 5 years, except nonmelanoma skin cancer
• No other medical history or condition that, in the opinion of the investigator, would preclude study participation
• No peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

• Recovered from all prior therapy
• No prior anti-cancer therapy that would preclude study therapy
• No prior anti-VEGF drugs, including bevacizumab
• No prior chemotherapy unless given concurrently with radiotherapy
  • Prior paclitaxel and/or topotecan with radiotherapy not allowed
• At least 6 weeks since prior chemoradiotherapy
• At least 3 weeks since prior radiotherapy alone
• More than 28 days since prior major surgery or open biopsy
• More than 7 days since prior core biopsy
• No concurrent major surgery including, but not limited to, abdominal surgery prior to disease progression (e.g., colostomy or enterostomy reversal, interval or secondary cytoreductive surgery, or second-look surgery via laparotomy or laparoscopy)