• Objective response rate [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]
• Quality of life parameters as measured by standard, validated, age-calibrated performance, pain, and mood scales [ Designated as safety issue: No ]
• Perception of treatment impact on patient self-identified worst symptoms as measured by numeric assessment tools [ Designated as safety issue: No ]

• Objective response rate
• Toxicity
• Quality of life parameters as measured by standard, validated, age-calibrated performance, pain, and mood scales
• Perception of treatment impact on patient self-identified worst symptoms as measured by numeric assessment tools

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining methotrexate with vinblastine may be effective treatment for neurofibromatosis type 1 associated with progressive plexiform neurofibromas.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have neurofibromatosis type 1 associated with progressive plexiform neurofibromas.

OBJECTIVES:

• Determine the effect of chronic vinblastine and methotrexate on time to disease progression in children or young adults with progressive plexiform neurofibroma associated with neurofibromatosis type 1.
• Determine the objective response rate in patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.
• Determine the quality of life of patients treated with this regimen.

OUTLINE: Patients are stratified according to tumor status (severely debilitating and/or life-threatening vs cosmetically disfiguring).

Patients receive methotrexate and vinblastine IV weekly for 26 weeks and then every 2 weeks for 26 weeks in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months during study participation.

Patients are followed every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study within approximately 3 years.

• Neurofibromatosis Type 1
• Precancerous/Nonmalignant Condition

• Drug: methotrexate
• Drug: vinblastine

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