Combination Chemotherapy in Treating Patients With Neurofibromatosis and Progressive Plexiform Neurofibromas

Inclusion Criteria:

1. Progressive, debilitating, severely disfiguring or life-threatening plexiform neurofibroma (PN) which is not surgically resectable and for which there is no other standard medical management. Histologic confirmation of tumor is not required in the presence of consistent clinical and radiographic findings. However, if any clinical observation or scan suggests possible malignant transformation, the tumor must be biopsied prior to therapy. In addition to PN, all study subjects must have at least one other diagnostic criteria for Neurofibromatosis type 1 (NF1) listed below:

   * 6 or more café-au-lait spots \> 0.5 cm in prepubertal subjects or \> 1.5 cm in postpubertal subjects
   * freckling in the axilla or groin
   * optic glioma
   * 2 or more lisch nodules
   * a distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
   * a first degree relative with NF1
2. Adequate bone marrow, renal, hepatic function:

   * Absolute Neutrophil Count (ANC)\> 1000 and platelet count \>100,000 prior to initiation of therapy
   * must have normal renal function: Blood Urea Nitrogen (BUN)/Creatinine \<1.5x normal for age), alkaline phosphatase (ALP), albumin, total protein and bilirubin
   * must have normal liver function: Bilirubin, alanine transaminase (ALT), aspartate aminotransferase (AST) \< 1.5x normal for age
3. Patients must have measurable PN by direct physical examination (documented by clinical measurement of tumor and serial photography) or by imaging studies. Most patients will have tumors that can be measured by magnetic resonance imaging (MRI), however, some patients may have cosmetically disfiguring PN which would be best measured clinically and with serial photography throughout treatment and follow-up. A measurable lesion is one whose size can be quantified in at least 2 dimensions. There must be evidence of recurrent or progressive disease as documented by an increase in size or the presence of new lesions on MRI. Progression is defined as the 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 \< 12 months prior to evaluation for this study. For purposes of this study, index PN lesions will be those PNs evaluated as the most life-threatening, debilitating, cosmetically disfiguring, and/or most easily measured.
4. Prior therapy: Patients with NF1 are eligible at the time of recurrence or progression of inoperable PN. A surgical consultation should be obtained prior to enrollment on the study to evaluate if tumor resection is a feasible option. Patients will only be eligible if complete tumor resection is not feasible or if a patient with a surgical option refuses surgery. Since there is no standard effective chemotherapy for patients with NF1 and progressive PN, patients may be treated on this trial without having received prior therapy. Patients must have recovered from the toxic effects of all prior therapy before entering this study. The Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0 will be used for toxicity assessment. Recovery is defined as a toxicity grade \< 2, unless otherwise specified in the Inclusion and Exclusion Criteria. Patients must have had their last dose of radiation therapy at least 6 weeks prior to study entry, and their last dose of chemotherapy at least four weeks prior to study entry. Patients who received granulocyte-colony stimulating factor (G-CSF) after the prior cycle of chemotherapy must be off G-CSF for at least one week prior to entering this study.
5. Performance status: Patients should have a life expectancy of at least 12 months and a Lansky or Karnofsky performance score of \> 60. Patients who are wheelchair bound because of paralysis should be considered "ambulatory" when they are mobile and active in their wheelchairs rather than actually ambulatory.
6. A Pregnancy test must be negative for females of childbearing age.
7. Informed consent: All patients or their legal guardians (if the patient is less than 18 years old) must sign an approved document of informed consent indicating their understanding of the investigational nature and the risks of this study before beginning therapy. When appropriate pediatric patients will be included in all discussion in order to obtain verbal assent.

Exclusion Criteria:

1. Pregnant females are excluded
2. Patient has had treatment with an investigational agent within the past 30 days.
3. Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor or immunotherapy.
4. Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity and response to therapy.