Vinblastine/Methotrexate For Severe Progressive Plexiform Neurofibromas: A Phase II Study

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of progressive, debilitating, severely disfiguring, or life-threatening
plexiform neurofibroma (PN) that is surgically unresectable (or surgery refused by
patient) and for which there is no other standard medical management

- Histologic confirmation of tumor not required in the presence of consistent
clinical and radiographic findings

- Tumor must be biopsied if any clinical observation or scan suggests
possible malignant transformation

- Measurable disease

- PN lesion that can be measured in at least 2 dimensions by direct physical
examination (clinical measurement and serial photography) or MRI

- Recurrent or progressive disease as documented by an increase in size or the presence
of new lesions on MRI

- Appearance of new tumors or a measurable increase in the sum of the product of
the two longest perpendicular diameters of the index lesion(s) over a time
period of no more than 12 months prior to study entry

- Must meet at least one other diagnostic criteria for neurofibromatosis type 1 (NF1):

- Six or more cafe-au-lait spots at least 0.5 cm in prepubertal patients or at
least 1.5 cm in postpubertal patients

- Freckling in the axilla or groin

- Optic glioma

- Two or more Lisch nodules

- Distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning
of long bone cortex)

- First-degree relative with NF1

- Prior therapy for NF1 or PN is not required

PATIENT CHARACTERISTICS:

Age:

- 25 and under

Performance status:

- Lansky 60-100% OR

- Karnofsky 60-100%

Life expectancy:

- At least 12 months

Hematopoietic:

- CBC normal

- Absolute neutrophil count greater than 1,000/mm^3

- Platelet count greater than 100,000/mm^3

Hepatic:

- Bilirubin no greater than 1.5 times normal

- ALT/AST no greater than 1.5 times normal

Renal:

- BUN no greater than 1.5 times normal

- Creatinine no greater than 1.5 times normal

Other:

- Not pregnant or nursing

- Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 1 week since prior filgrastim (G-CSF)

- No concurrent immunotherapy

Chemotherapy:

- At least 4 weeks since prior chemotherapy

- No other concurrent chemotherapy

Endocrine therapy:

- No concurrent hormonal therapy directed at the tumor

Radiotherapy:

- At least 6 weeks since prior radiotherapy

- No concurrent radiotherapy

Surgery:

- See Disease Characteristics

Other:

- Recovered from any prior therapy

- At least 30 days since prior investigational agents