RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing
so they stop growing or die. Combining chemotherapy with peripheral stem cell
transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill
more tumor cells.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together
with bone marrow transplantation or peripheral stem cell transplantation works in treating
patients with relapsed germ cell cancer.
- Estimate the antitumor activity of 2 courses of paclitaxel and carboplatin regimens
with autologous stem cell rescue in patients with relapsed germ cell cancer.
- Evaluate the toxic effects of paclitaxel, carboplatin and etoposide (VP-16) with stem
cell support followed by paclitaxel, carboplatin and ifosfamide with stem cell support
in these patients.
OUTLINE: Patients receive filgrastim (G-CSF) SC or IV 4 days prior to peripheral blood stem
cells (PBSC) apheresis. Autologous bone marrow harvest is performed when adequate stem cells
cannot be collected.
Patients then receive course 1 of high-dose chemotherapy beginning on day -7 with paclitaxel
IV over 24 hours. On days -6 to -4, patients receive etoposide IV over 2 hours and
carboplatin (CBDCA) IV over 30 minutes 3 times daily. Following a 2 or 3 week recovery, a
second course of chemotherapy begins on day -7, consisting of paclitaxel IV over 24 hours,
then CBDCA and ifosfamide on days -6 to -4.
Reinfusion of PBSC and marrow begins on day -2 in both course 1 and 2. In addition, G-CSF IV
is given twice a day until 3 consecutive postnadir days of granulocytes of at least
1000/mm^3 are maintained. On day 0, stem cells with or without bone marrow product are again
Surgery may be performed after course 2 if indicated.
PROJECTED ACCRUAL: The expected accrual rate is 12 patients per year over 2 years.
- Evaluable germ cell cancer (measurable by radiographic study and/or serum tumor
marker elevation) and not curable by standard salvage therapy OR viable cancer on
resection of post-chemotherapy residual masses in either intermediate or high risk
- Bidimensionally measurable disease with measurements performed within 21 days of
- Tumor marker (alpha-fetoprotein, lactate dehydrogenase, beta-human chorionic
gonadotropin) studies performed within 7 days prior to study entry
- 16 and over
- Karnofsky 70-100%
- Not specified
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 120,000/mm^3
- Hemoglobin at least 10 g/dL
- Bilirubin no greater than 1.6 mg/dL
- SGOT and SGPT no greater than 2 times upper limit of normal (ULN)
- No active hepatitis or cirrhosis
- Creatinine clearance at least 70 mL/min
- Ejection fraction (MUGA or echocardiogram) normal
- No EKG evidence of active cardiac disease (arrhythmias, ischemia) which would
contraindicate etoposide and paclitaxel study treatment
- PaO_2 at least 70 mm Hg
- FEV_1 at least 2 L or 75%
- No history of bleomycin associated or serious lung disease
- No steroid or glucocorticoid treatment for patients with CNS metastatic disease; at
least 1 month with stable post-radiotherapy neurological status and seizure free; if
prior seizures, at least 1 month with therapeutic anticonvulsant levels prior to
- Prior peripheral neuropathy requires consultation with principal investigator
- No significant active medical illness precluding study or survival
- Not HIV positive
- No prior malignancy within past 5 years except for adequately treated basal cell or
squamous cell skin cancer
- No prior hematologic malignancies
PRIOR CONCURRENT THERAPY:
- No prior bone marrow or stem cell rescue with high-dose chemotherapy
- Prior chemotherapy allowed, excluding high-dose therapy with bone marrow or stem cell
- No prior paclitaxel
- Not specified
- No concurrent radiotherapy during study
- Recovered from prior surgery