Combination Chemotherapy Followed by Bone Marrow Transplantation in Treating Patients With Rare Cancer

Myeloablative Chemotherapy With Bone Marrow Rescue For Rare Poor-Prognosis Cancers

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Bone marrow transplantation may allow doctors to give higher doses of chemotherapy and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy with thiotepa, carboplatin, and topotecan followed by bone marrow transplantation in treating patients who have metastatic or progressive rare cancer.

OBJECTIVES:

• Improve the long term disease-free survival of patients with rare cancers at high risk for lethal relapse by using myeloablative chemotherapy with thiotepa, carboplatin, and topotecan followed by autologous bone marrow or peripheral blood stem cell rescue.

OUTLINE: Autologous bone marrow or peripheral blood stem cells (PBSC) are harvested. Patients receive high-dose thiotepa IV over 3 hours on days -8 to -6, carboplatin IV over 4 hours on days -5 to -3, and topotecan IV over 30 minutes on days -8 to -4. Autologous bone marrow or PBSC are reinfused on day 0. Patients receive filgrastim (G-CSF) IV twice daily beginning on day 1.

Patients are followed for 1 year.

PROJECTED ACCRUAL: Approximately 50 patients will be accrued for this study within 5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy of one of the following types:

  • Wilms' tumor
  • Liver cancer
  • Desmoplastic or other small round cell tumor
  • Nasopharyngeal carcinoma
  • Fibrosarcoma

• Disease that has metastasized and has a cure rate of no greater than 25% with conventional treatment or disease that has progressed after prior chemotherapy, was not then surgically resectable, and has a salvage rate with nonmyeloablative therapies of no greater than 25% required

• Maximal benefit from conventional (nonmyeloablative) doses of combination chemotherapy required prior to entry, and it is recommended that patients have received a minimum of one of the following:

  • 2 courses of high-dose cyclophosphamide (as per protocol MSKCC-90062)
  • 2 courses of high-dose ifosfamide/etoposide (as in the poor-risk sarcoma protocol MSKCC-90071A)
  • 1 course of high-dose cyclophosphamide plus 1 course of high-dose ifosfamide/etoposide

• Within 3 weeks of initiation of protocol therapy, patients must be:

  • In CR or good PR OR
  • Tumor considered "chemosensitive", i.e., a 50% or greater decrease in at least 1 measurable tumor parameter attributable to prior chemotherapy without evidence of progressive disease by any other parameter

• Ineligible for other IRB-approved myeloablative regimens

• No evidence of current bone marrow involvement on bone marrow aspiration (x4) and biopsy (x2)

PATIENT CHARACTERISTICS:

Age:

• 21 and under

Performance status:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 1.5 times ULN
• Alkaline phosphatase no greater than 1.5 times ULN
• 5'-Nucleotidase no greater than 1.5 times ULN

Renal:

• Creatinine normal
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• CPK normal
• Echocardiogram (or RNCA) normal
• EKG normal

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics