Chemotherapy is very rarely used for treating meningioma although research continues into developing this form of treatment. Hydroxyurea appears to have modest activity against meningiomas and should be considered in patients with unresectable tumors or large residual tumors following surgical resection. Hydroxyurea, an inhibitor of ribonucleotide reductase, is one of the most active agents and is known to induce death of meningioma cells. Results of preliminary clinical studies suggest that hydro xyurea has modest activity against recurrent and inoperable meningiomas, and can induce long term stabilization in some patients. However, the results are conflicting and a few clinical trials did not show positive results. In the authors' initial report of 17 patients with meningioma, hydroxyurea demonstrated modest efficacy, with a median time to progression (TTP) of 80 weeks. In the current study, 21 patients with meningioma have been placed on hydroxyurea (20 mg/kg/day orally), with extended follow-up of the original cohort. Eighteen of 20 evaluable patients (90%) responded with stable disease ranging from 20 to 328 + weeks (median TTP 176 weeks; 11 patients censored). Five of the stabilized patients progressed after 20, 56, 36, 216 and 56 weeks, respectively. Two patients had progressive disease after 10 weeks. Toxicity was mainly haematological. Hydroxyurea has modest activity against meningiomas and should be considered for patients who are poor surgical candidates, have unresectable or large resi dual meningiomas, or have progressed after surgical resection or irradiation, or both. SIDE EFFECTS Adverse reactions have been primarily bone marrow depression (increased risk for infection, anemia, and occasionally a decrease of platelets in blood), and less frequently gastrointestinal symptoms (stomatitis, anorexia, nausea, vomiting, diarrhea, and constipation), and dermatological reactions such as little spots or bumps, skin ulceration, inflammation of the muscles and the skin, peripheral and facial redness. Skin cancer has been reported. Fever, chills, malaise, edema, asthenia, and elevation of hepatic enzymes have also been reported. Adverse reactions observed with combined hydroxyurea and irradiation therapy are similar to those reported with the use of hydroxyurea or radiation treatment alone. These effects primarily include bone marrow depression (anemia and increased risk for infection), gastric irritation, and painful inflammation and ulceration of the mucous membranes lining the digestive tract. Almost all patients receiving an adequate course of combined hydroxyurea and irradiation therapy will demonstrate concurrent leukopenia. HYDREA may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.
Recurrent, irresectable meningioma constitutes an uncommon but significant problem. Many systemic therapies have been tested without clear evidence of efficacy. More recently, two reports have suggested that hydroxyurea has activity in this context. This study examined the efficacy and toxicity of hydroxyurea in the treatment of 15 patients with high risk meningioma, residual meningioma post resection and progressive meningioma. Hydroxyurea was well tolerated although two patients ceased therapy because of skin rashes. There were no objective responses. Eleven patients achieved stable disease including eight patients who had documented progression prior to commencing hydroxyurea. These results are consistent with previous reports. In conclusion, hydroxyurea may provide some clinical benefit in patients with progressive meningioma by delaying progression of disease. Chemotherapy and Other Drug Therapy Chemotherapy is very rarely used in the treatment of meningioma. Chemotherapy has not been shown to be effective for meningiomas. However, in instances where surgery and further radiation are no longer feasible or safe, Mayo physicians may recommend possible chemotherapy options. October 14, 1996 4 Patients. None of the patients had any problematic side effects. The maximum dose did not exceed 20 mg/kg/day, and was well tolerated. With respect to hematological toxicity, none of the patients experienced significant bone marrow suppression. If the white blood cell count fell below 3000/µl the dose was reduced for a few days. The most common nonhematological side effects were mild fatigue in two, bleeding of the gums in three, and constipation in two patients. DISCUSSION The shrinkage of the tumor was accompanied by a complete remission of the trigeminal neuralgia after 2 months and by improved extraocular muscle function after 5 months of treatment. Another patient with a slowly growing left-sided cavernous sinus meningioma (Case 3) and symptomatic trigeminal neuralgia achieved a minor decrease in tumor size (15%) and remission of her neuralgia after 5 months of treatment. The patient with the malignant Grade III meningioma in the left posterior fossa (cerebellopontine angle, Case 4), who was treated with hydroxyurea immediately after his sixth palliative operation without awaiting his next relapse, has not experienced recurrence during the 24-month course of hydroxyurea therapy. This is the first report of a successful use of hydroxyurea in the medical treatment of unresectable and recurrent benign as well as malignant meningiomas. However, when the meningioma is unresectable and/or all other previous treatments have failed, immunotherapy or chemotherapy may be considered for malignant tumors and immunotherapy and hormone therapy may be considered for benign ones. The most effective immunotherapy appears to be administration of interferon-alpha, which is relatively non-toxic and easily tolerated.