• 2-year relapse-free survival rate [ Designated as safety issue: No ]
  

OBJECTIVES:

• To estimate the two-year relapse-free survival rates and compare them with historical experience from the City of Hope and published literature.

OUTLINE: Patients are stratified according to disease status (chemo-responsive first relapse vs marker negative after chemotherapy but viable tumor at surgical resection vs all other patients [second relapse, responding to third-line therapy, and no history of absolute refractoriness to platinum-based therapy] vs patients with mediastinal primary nonseminomatous germ cell tumors not in subsequent relapse and not refractory to first-line therapy) and prior therapy with paclitaxel and ifosfamide-containing regimens (yes vs no).

• Peripheral blood hematopoietic stem cell (PBSC) collection: Patients are mobilized with cyclophosphamide IV over 2 hours. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or IV beginning 24 hours after the start of cyclophosphamide and continuing through the completion of apheresis. Patients undergo apheresis beginning on approximately 10 days after mobilization and continue until a minimum of 4 x 10^6 CD34 cells/kg are collected. Peripheral cells are processed and cryopreserved following standard methods at the City of Hope.

• Tandem high-dose chemotherapy and PBSC reinfusion:

  • Course 1: Patients receive paclitaxel IV over 24 hours on day -6, etoposide IV over 2 hours and carboplatin IV over 30 minutes on days -5 to -3, and G-CSF IV daily beginning on day 2 and continuing until blood counts recover. Patients undergo autologous PBSC transplantation on days -2 and 0.
  • Course 2: Beginning 2-3 weeks after completion of course 1, patients receive paclitaxel IV over 24 hours on day -7, ifosfamide IV over 30 minutes and carboplatin IV over 30 minutes on days -6 to -4, and G-CSF IV daily beginning on day -2 and continuing until blood counts recover. Patients undergo autologous PBSC transplantation on days -2 and 0.

After completion of study treatment, patients are followed monthly for 1 year, every 2 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then yearly thereafter.

DISEASE CHARACTERISTICS:

• Histologically confirmed seminoma or nonseminoma germ cell cancer

  • Male patients only
  • Females with dysgerminoma or other germ cell cancers are eligible but will not be included in the primary analysis

• Tumor-free but remain at high risk OR meeting 1 of the following criteria:

  • Marker negative after chemotherapy with surgical resection of residual cancer (s-CR)*

  • Chemo-responsive first relapse*

    • Patients in first relapse responding to second-line therapy with a taxane- or non-taxane-based regimen

      • Paclitaxel plus ifosfamide-based regimen
      • Non-paclitaxel plus ifosfamide-based regimen

  • All other patients meeting the following criteria:

    • Second relapse
    • Responding to third-line therapy
    • No history of absolute refractoriness to platinum-based therapy NOTE: *Patients with mediastinal primary nonseminomatous germ cell cancer (NSGCT) are eligible provided they are not in subsequent relapse and not refractory to first-line therapy.
• Evaluable disease (measurable by radiographic study and/or serum tumor marker elevation)

• History of CNS metastases allowed provided the patient has been treated and off steroids with stable post-radiotherapy neurological status for at least 1 month and seizure-free for at least 1 month with therapeutic anticonvulsant levels prior to registration

  • The presence of peripheral neuropathy will not be an absolute contraindication but should be discussed with the principal investigator

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Creatinine clearance ≥ 60 mL/min
• Bilirubin ≤ upper limit of normal (ULN) (or indirect bilirubin ≤ 2.5 times ULN if the patient has Gilbert syndrome)
• ALT and AST ≤ 3 times ULN (no liver involvement) or ≤ 4 times ULN (if liver involvement)
• ANC ≥ 1,500/μL
• Platelets ≥ 120,000/μL
• Hemoglobin ≥ 10 g/dL (may be transfused or receive epoetin alfa, but may not be treated with colony-stimulating factors or platelet transfusions)
• Ejection fraction normal by MUGA or echocardiogram

• No prior invasive malignancy except for adequately treated nonmelanoma skin cancer or other cancers from which the patient has been disease-free for at least 5 years

  • Prior hematologic malignancies are excluded
• No EKG evidence of active cardiac disease (i.e., arrhythmias or ischemia) that would contraindicate the administration of etoposide and paclitaxel
• Room air PaO_2 ≥ 70 mm Hg

• FEV_1 ≥ 2 liters or 75% of lower limit of predicted value

  • No history of clinically significant bleomycin-associated or other serious lung disease
• HIV negative
• Patients with seropositivity for hepatitis B surface antigen or hepatitis C antibody must have a liver biopsy showing no evidence of active hepatitis or cirrhosis
• Must have recovered from major infections and, in the opinion of the investigator, not have significant active medical illness precluding protocol treatment or survival

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior surgery
• No expected need for radiotherapy during the protocol treatment period