ABSTRACT
PURPOSE: Aggressive meningiomas that progress after surgery/radiotherapy represent an unmet medical need. Strong and constant expression of SSTR2A receptors and activation of the Pi3K/Akt/mTOR pathway have been demonstrated in meningiomas. The combination of everolimus, an mTOR inhibitor, and octreotide, a somatostatin agonist, has shown additive antitumor effect in vitro. The phase II CEVOREM trial investigated the efficacy of this combination on recurrent meningiomas. PATIENTS AND METHODS: Patients with documented recurrent tumor progression ineligible for further surgery/radiotherapy were eligible to receive octreotide (30 mg/d, day 1) and everolimus (10 mg/d, days 1-28). The primary endpoint was the 6-month progression-free survival rate (PFS6). The secondary endpoints were overall survival, response rate, tumor growth rate according to central review, and safety. RESULTS: A total of 20 patients were enrolled, including 2 with World Health Organization (WHO) grade I tumors, 10 with WHO grade II tumors, and 8 with WHO grade III tumors; furthermore, 4 patients harbored NF2 germline mutation. The overall PFS6 was 55% [95% confidence interval (CI), 31.3%-73.5%], and overall 6- and 12-month survival rates were 90% (95% CI, 65.6%-97.4%) and 75% (95% CI, 50.0%-88.7%), respectively. A major decrease (>50%) was observed in the growth rate at 3 months in 78% of tumors. The median tumor growth rate decreased from 16.6%/3 months before inclusion to 0.02%/3 months at 3 months (P < 0.0002) and 0.48%/3 months at 6 months after treatment (P < 0.0003). CONCLUSIONS: The combination of everolimus and octreotide was associated with clinical and radiological activity in aggressive meningiomas and warrants further studies. Decrease in the tumor volume growth rate should be considered a complementary and sensitive endpoint to select potentially effective drugs for recurrent meningiomas.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Meningeal Neoplasms/drug therapy , Meningioma/drug therapy , Neoplasm Recurrence, Local/drug therapy , Receptors, Somatostatin/antagonists & inhibitors , TOR Serine-Threonine Kinases/antagonists & inhibitors , Tumor Burden/drug effects , Adult , Aged , Everolimus/administration & dosage , Female , Humans , Male , Meningeal Neoplasms/metabolism , Meningeal Neoplasms/pathology , Meningioma/metabolism , Meningioma/pathology , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Octreotide/administration & dosage , Patient Safety , Prospective Studies , Survival Rate , Treatment OutcomeABSTRACT
Improvement of diagnosis techniques and cancer treatment efficacy explain in part the increasing incidence of brain metastasis, observed in 20 to 30 % of cancer patients. New techniques of MRI improve its sensibility and guide therapeutic decision, in conjunction with prognostic factors including age, Karnovsky performance score and control of the general disease. Surgical excision is mainly indicated for single metastasis in none functional area, or in case of mass effect, while radiosurgery represents an alternative non invasive technique, particularly for single small lesions. In other cases, whole brain radiation therapy remains the treatment of choice for brain metastasis, while no clear data support it use complementary to surgery. Chemotherapy has no proven efficacy as part of first line treatment of patients with brain metastasis and still warren further research.
Subject(s)
Brain Neoplasms/secondary , Brain Neoplasms/therapy , Administration, Oral , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Age Factors , Aged , Brain Neoplasms/diagnosis , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Brain Neoplasms/mortality , Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Breast Neoplasms , Colonic Neoplasms , Combined Modality Therapy , Humans , Karnofsky Performance Status , Kidney Neoplasms , Lung Neoplasms , Lymphoma/diagnosis , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Middle Aged , Neoplasm Recurrence, Local , Positron-Emission Tomography , Prognosis , Radiosurgery , ResearchABSTRACT
Although many patients with oligodendrogliomas (ODs) and oligoastrocytomas (OAs) benefit from a combination of surgery and adjuvant radiotherapy, most patients eventually experience recurrence of their disease. Recent evidence has shown that ODs are more chemosensitive than other gliomas, including astrocytomas or glioblastoma multiforme. These initial findings have prompted further study of chemotherapy in treating ODs and mixed OAs. Advances in molecular genetic analysis have led to improvements in predicting response to chemotherapy and prognosis for ODs, OAs, and astrocytomas. Pure ODs are more chemosensitive than mixed ODs. This difference is related to different proportions of 1p/19q loss of heterozygosity in these neoplasms. Therefore, genetic analysis is likely to be key in determining appropriate treatment. The most common first-line chemotherapy for patients with OD is a procarbazine, lomustine, and vincristine (PCV) combination regimen. However, this regimen is associated with cumulative myelosuppression, nausea, vomiting, and weight loss. Therefore, other chemotherapy agents and regimens have been investigated. Perhaps the most promising is temozolomide, a novel alkylating agent that freely crosses the blood-brain barrier. Temozolomide is approved in the United States for the treatment of recurrent anaplastic astrocytomas and in Europe for any recurrent high-grade gliomas. Initial reports suggest that temozolomide is effective in treating ODs as first- and second-line chemotherapy. Unlike the PCV regimen, temozolomide is not associated with cumulative myelosuppression and is usually well tolerated. Further studies are needed to confirm the efficacy and safety profile of temozolomide and to determine the optimal dose and schedule for treating ODs.
