Phase II study of subcutaneous octreotide in adults with recurrent or progressive meningioma and meningeal hemangiopericytoma.

The objective of this phase II study was to evaluate the efficacy and safety of subcutaneous octreotide therapy for the treatment of recurrent meningioma and meningeal hemangiopericytoma. Octreotide is an agonist of somatostatin receptors, which are frequently expressed in meningioma, and reports have suggested that treatment with somatostatin agonists may lead to objective response in meningioma. Patients with recurrent/progressive meningioma or meningeal hemangiopericytoma were eligible for enrollment; those with atypical/anaplastic meningioma or hemangiopericytoma must have experienced disease progression despite radiotherapy or have had a contraindication to radiation. Patients received subcutaneous octreotide with a goal dose of 500 µg 3 times per day, as tolerated. Imaging was performed every 3 months during therapy. The primary outcome measure was radiographic response rate. Eleven patients with meningioma and 1 with meningeal hemangiopericytoma were enrolled during the period 1992-1998. Side effects included diarrhea (grade 1 in 4 patients and grade 2 in 2), nausea or anorexia (grade 1 in 4 patients), and transaminitis (grade 1 in 1 patient). One patient developed extra hepatic cholangiocarcinoma, which was likely unrelated to octreotide therapy. No radiographic responses were observed. Eleven of the 12 patients experienced progression, with a median time to progression of 17 weeks. Two patients experienced long progression-free intervals (30 months and ≥18 years). Eleven patients have died. Median duration of survival was 2.7 years. Immunohistochemical staining of somatostatin receptor Sstr2a expression in a subset of patients did not reveal a correlation between level of expression and length of progression-free survival. Octreotide was well-tolerated but failed to produce objective tumor response, although 2 patients experienced prolonged stability of previously progressive tumors.

Immunomodulatory treatment trial for paraneoplastic neurological disorders.

Paraneoplastic neurological disorders are devastating remote effects of malignancy. Despite compelling evidence of an autoimmune pathogenesis, empiric immunomodulatory treatment of these disorders is often ineffective. However, very few systematic studies have been conducted, and the treatment of patients without active malignancy has not been addressed. We conducted a prospective open-label treatment study of plasma exchange plus conventional cancer chemotherapy (10 patients) or plasma exchange plus continuous oral cyclophosphamide (10 patients). All patients had progressive symptoms and at least moderate disability at enrollment (mean Rankin score, 3.4). Patients who had experienced symptoms for more than 12 months were excluded (mean duration of symptoms at enrollment, 3.6 months). The primary outcome measure was change in quantitative disability measures (Rankin and Barthel scores) after 6 months of treatment; a positive response was defined as stability or improvement in disability. Overall, 50% of patients had a positive response at 6 months (6 patients had improved by at least 1 Rankin grade). Patients with good outcome tended to be those with less disability at time of enrollment. Hematologic toxicity was common among those receiving cyclophosphamide. Aggressive immunosuppression early in the clinical course should be considered in patients who have paraneoplastic neurological disorders, even when there is no evidence of active malignancy.

Risk of cancer among relatives of patients with glioma.

We report a population-based, retrospective study of 396 Icelandic people diagnosed with glioma in the years 1940-1995. The purpose of this study was to test whether astrocytomas, other glial tumors, other central nervous system tumors, or other cancers aggregate in families identified through glioma probands who were of Icelandic origin. Pedigrees of the 396 cases were traced by the Genetical Committee of the University of Iceland and linked to the Icelandic Cancer Registry. A total of 25,546 relatives, including 2,080 individuals with cancer were identified within these pedigrees. There was no statistically significant increase of glioma in relatives of glioma patients, nor was there any statistically significant increase in risk for other central nervous system tumors. There was no overall increase in incidence of all cancer combined, nor of specific common cancers (lung, prostate, breast, stomach, and colorectal) and uncommon cancers (melanoma and pancreas) in the relatives of glioma patients. Our results do not support the hypothesis of a familial aggregation of glioma indicative of a glioma susceptibility gene.