A Phase I Study Of Oral Irinotecan, Temozolomide, Cefixime In Children With Recurrent/Resistant High-Risk Neuroblastoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed neuroblastoma AND/OR demonstration of tumor cells in the
bone marrow with increased urinary catecholamines

- High-risk disease meeting 1 of the following criteria:

- Recurrent or progressive disease

- Resistant or refractory disease (i.e., never achieved a complete response
to therapy AND never had new sites of disease or progression of initial
sites)

- Measurable disease meeting at least 1 of the following criteria:

- Unidimensionally measurable tumor ≥ 20 mm by MRI, CT scan, or x-ray OR ≥ 10 mm
by spiral CT scan*

- At least 1 site with positive uptake by metaiodobenzylguanidine (MIBG) scan*

- Bone marrow with tumor cells seen on routine morphology (not by NSE staining
only) of bilateral aspirate AND/OR biopsy on 1 bone marrow sample NOTE:
*Patients who never experienced disease recurrence or progression must
demonstrate viable neuroblastoma in a biopsy of either bone marrow or bone
and/or soft tissue site (biopsy must be performed ≥ 4 weeks after completion of
prior radiotherapy if lesion was irradiated)

PATIENT CHARACTERISTICS:

Age

- 1 to 30 at diagnosis

Performance status

- ECOG 0-2

Life expectancy

- At least 2 months

Hematopoietic

- Absolute neutrophil count ≥ 750/mm^3

- Platelet count ≥ 75,000/mm^3 (without transfusion)

- Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

Hepatic

- SGPT and SGOT < 5 times normal

- Bilirubin ≤ 1.5 times normal

Renal

- Creatinine ≤ 1.5 times normal for age

- No greater than 0.8 mg/dL (≤ 5 years of age)

- No greater than 1.0 mg/dL (6 to 10 years of age)

- No greater than 1.2 mg/dL (11 to 15 years of age)

- No greater than 1.5 mg/dL (> 15 years of age)

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No allergy to cephalosporins

- No active diarrhea

- No uncontrolled infection

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Chemotherapy

- Recovered from prior immunotherapy

- More than 3 weeks since prior biologic therapy and recovered

- More than 2 days since prior hematopoietic growth factors

- No concurrent epoetin alfa

- No concurrent prophylactic hematopoietic growth factors during the first treatment
course

- No concurrent immunomodulating agents except steroids to control intracranial
pressure

Chemotherapy

- Prior myeloablative therapy and autologous stem cell transplantation allowed

- No prior allogeneic stem cell transplantation

- More than 3 weeks since prior myelosuppressive chemotherapy (4 weeks for
nitrosoureas) and recovered

- Prior temozolomide, irinotecan, or topotecan allowed

- No prior temozolomide and irinotecan as combination therapy

- No other concurrent chemotherapy

Endocrine therapy

- See Biologic therapy

Radiotherapy

- At least 6 weeks since prior large field radiotherapy (e.g., total body irradiation,
craniospinal therapy, whole abdomen, total lung, or > 50% bone marrow space) and
recovered

- At least 4 weeks since prior radiotherapy to biopsied lesions (for study entry) and
recovered

- At least 6 weeks since prior MIBG therapy

- Concurrent radiotherapy to painful lesions allowed provided the lesions are not used
to assess treatment response

Surgery

- Not specified

Other

- No concurrent enzyme-inducing anticonvulsants (e.g., phenobarbital, phenytoin, or
carbamazepine)

- No other concurrent anticancer agents