As a rule paragangliomas are solitary slow-growing lesions with malignancy difficult to determine histologically and is usually based on the presence of metastatic disease [1].

A combination on therapeutic modalities is needed for adequate treatment of these lesions. In the setting of residual and metastatic disease, chemotherapy rises as an interesting option in the treatment. Even with this aim, currently, there is a paucity of data regarding chemotherapy for paragangliomas. The biggest series showed conflicting results. Patel (1995) published a 15-year experience with paragangliomas and reported some benefit with doxorubicin, dacarbazine, and cyclophosphamide but the same regime was considered ineffective by Massey and Wallner (1992). Since these series, only a few case reports with promising results using gemcitabine and sorafenib have been published but no prospective randomized trial is available in the literature. In conclusion, there is no effective chemotherapy agent in the treatment of benign jugular foramen paragangliomas and surgery remains the treatment of choice [2, 3].

Malignant paragangliomas presents a survival rate between 34 % and 60 %. Treatment of these tumors remains a challenge. Gillon et al. treated successfully with metronomic cyclophosphamide two patients with malignant paragangliomas . Sunitinib is a tyrosine kinase inhibitor with promising antiangiogenic effect and immune stimulation [4]. Treatment with 131l-MIBG was reported to induce tumor remission in a coexisting paraganglioma of the retroperitoneum and urinary bladder and combined therapy with 131I-MIBG and Sunitinib in a patient with metastatic paraganglioma (hereditary paraganglioma-pheochromocytoma syndrome) [5, 6].

The jugular foramen structures have embryological and histological ability to develop extracranial meningiomas [7]. Within the jugular foramen, the cranial nerves are not covered by dura; they are involved with connective mesodermic tissue [8].

In general, meningiomas are the most common intracranial neoplasm constituting 20–30 % of all primary brain tumors. The World Health Organization (WHO) classifies meningiomas into three grades: grade 1-benign meningiomas; grade 2-atypical meningioma; and grade 3-anaplastic meningiomas. In meningiomas WHO grade 1, complete resection results in prolonged disease-free survival or cure.

In contrast, high grade meningiomas, despite initial surgical resection and multimodality radiotherapy, often recur and require re-treatment. In this scenario, systemic therapy appears as attractive option. At present, however, exists a limited number of available systemic therapy in the treatment of meningiomas.

Biochemical evidence suggests that almost 70 % of meningiomas are progesterone receptor positive and 30 % are estrogen receptor positive. This fact, added to the epidemiological female predominance, suggests that meningiomas growth may be hormone dependent [9, 10].

Other receptors have been demonstrated in meningiomas. As consequence, a variety of hormonal therapies have been utilized in the treatment of recurrent meningiomas which are not amenable to further surgery or radiotherapy. Against this first promising evidence, a great number of trials failed to demonstrate any additional benefit in these patients. Progesterone agonist (megestrol acetate) and antagonist (mifepristone) were used in some trials with no observed response when compared to placebo. Median progression-free survival was 10 months in mifepristone group and 12 months in the placebo arm [9–11]. Tamoxifen also was proved to be ineffective.

Interferon-alfa has been found to inhibit the growth of cultured human meningiomas cell line in vitro. In the largest study, 35 patients with recurrent unresectable and previously irradiated WHO grade 1 meningiomas were treated and an increased progression-free survival was seen in these patients although with no radiographic response, thus, suggesting interferon-alfa as an active agent against recurrent low grade meningioma [12].

Hydroxyurea was another biochemotherapy used in the subset of recurrent meningioma. In 1997, Schrell et al. demonstrated in vitro that hydroxyurea was a potent inhibitor of cultured meningioma cells by inducing apoptosis. After this first stimulating evidence, several clinical trials were conducted and just modest result was seen. Besides that, in many studies testing hydroxyurea, the patient had not failed to radiotherapy leading to a potential bias. These results demonstrate that hydroxyurea, although generally well tolerated and convenient, appears to have only limited activity [13, 14].

The same occurred with the calcium block channel agent, cyclophosphamide and vincristine which failed to demonstrate any benefit in recurrent malignant meningioma [9, 15].

Currently, molecular pathogenesis of meningiomas has gained interest. Overexpression of several growth factors including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), their receptors, and signal transduction pathways have been seen and, then, implicated in meningioma growth. Many trials have been conducted trying to demonstrate any benefit with these specific inhibitors as somatostatin analog (octreotid), epidermal growth factor receptor (EGFR) inhibitors (gefitinib), platelet-derived growth factor receptor (PDGFR) inhibitors (imatinib), but anyone showed definitive evidence of benefit [16, 17].

VEGF plays a central role in tumor angiogenesis and peritumoral edema. VEGF and VEGFR are expressed in meningiomas, and the level of expression increases with tumor grade. Trials testing these agents are very limited in number and associated toxicity is not fully clarified. These drugs are only cytostatic agents and require long-term usage, and more studies are needed to support their usage [18, 19].

Intracranial schwannomas represent approximately 8 % of all primary intracranial tumors [20]. Schwannomas arising from the jugular foramen are very rare and account for only 2.9 % of all intracranial schwannomas [21].

The treatment of jugular foramen schwannoma remains essentially surgical since currently there is no effective chemotherapy agent known for schwannoma in general. All trials published in literature are in the subset of neurofibromatosis patients with vestibular schwannoma. In these patients Bevacizumab have shown good results with tumor shrinkage and hearing preservation. Other drugs have been tested, as lapatinib (EGFR/ErbB2 inhibitor), but no strong evidence has been achieved. Surgery remains the only curative treatment for jugular foramen schwannomas.

Chordomas resist radiotherapy and cytotoxic chemotherapy is inefficient. A better understanding of the molecular biology of these tumors will help to develop more effective therapies [22]. Lebellec et al. [23] reviewed 19 articles published between 1990 and 2014 describing the activity of target therapies for chordomas. The best response with targeted therapies was disease stabilization in 52–69 % of cases. Hindi et al. [24] have treated 48 patients with inoperable and progressive chordomas (PDGFB/PDGFRB positive) with imatinib (a platelet-derived growth factor receptor inhibitor, 800 mg/day). The median duration of treatment was 7 months. At a median follow-up of 24.5 months the median PFS was 9.9 months. EGFR inhibitors (erlotinib, gefitinib, lapatinib) have demonstrated partial and sustained response in some cases [25, 26].