Orphan drugs in glioblastoma multiforme: a review

Figures & data

Table 1 List of orphan drugs with designation for primary brain tumors

Generic name	Designation date	Orphan designation
Bevacizumab	May 26, 2006	Treatment of malignant glioma
Cediranib	December 13, 2010	Treatment of glioblastoma
Cilengitide	May 27, 2005	Treatment of malignant glioma
Trabedersen	June 5, 2002	Treatment of malignant glioma
Hypericin	August 3, 2000	Treatment of glioblastoma multiforme
Erlotinib HCl	July 18, 2003	Treatment of malignant glioma
Polifeprosan 20 with carmustine	December 13, 1989	Treatment of malignant glioma
Temozolomide	October 5, 1998	Treatment of recurrent malignant glioma
Glioma Enzastaurin	September 19, 2005	Treatment of glioblastoma multiforme
Thalidomide	February 27, 1998	Treatment of primary brain malignancies
Carmustine	July 3, 2000	Treatment of intracranial malignancies
Procarbazine HCl	August 8, 2006	Treatment of malignant glioma
Afatinib	June 4, 2014	Treatment of malignant brain and central nervous system tumors

Table 2 List of orphan drug with designation for indications other than primary brain tumors

Generic name	Designation date	Orphan designation
Vorinostat	March 17, 2004	Treatment of mesothelioma
Bortezomib	January 15, 2003	Treatment of multiple myeloma
Rilotumumab	June 18, 2012	Treatment of gastric cancer including gastroesophageal junction adenocarcinoma
Romidepsin	September 30, 2004	Treatment of non- Hodgkin’s T-cell lymphomas
Dasatinib	November 28, 2005	Treatment of chronic myelogenous leukemia
Pazopanib	October 20, 2009	Treatment of soft tissue sarcomas
Temsirolimus	December 16, 2004	Treatment of renal cell carcinoma
Cetuximab	July 3, 2000	Treatment of squamous cell cancer of the head and neck in patients who express epidermal growth factor receptor
Tipifarnib	July 6, 2004	Treatment of acute myeloid leukemia
Fenretinide	October 5, 2005	Treatment of neuroblastoma
Sorafenib	October 8, 2004	Treatment of renal cell carcinoma
Hydroxyurea	October 1, 1990	Treatment of patients with sickle cell anemia as shown by the presence of hemoglobin S
Bendamustine	August 17, 2007	Treatment of chronic
HCI		lymphocytic leukemia
Gossypol	October 22, 1990	Treatment of cancer of the adrenal cortex

Table 3 Efficacy data from reported clinical trials in GBM with orphan drug designated for other indications

Drug rate	Phase	Patients (n)	Response	PFS6	Reference
vorinostat and bortezomib	II	Recurrent GBM (37)	0	0	Friday et al^Citation55
vorinostat	II	Recurrent GBM (66)	3%	15%	Galanis et al^Citation56
Rilotumumab	II	Recurrent GBM (61)	0	18%	Wen et al^Citation57
Romidepsin	II	Recurrent GBM (35)	0	3%	Iwamoto et al^Citation58
Dasatinib and bevacizumab	II	Recurrent GBM (14)	0	0	Lu-Emerson et al^Citation59
Pazopanib	II	Recurrent GBM* (35)	6%	3%	Iwamoto et al^Citation60
Imatinib	II	Recurrent GBM (51)	6%	16%	Raymond et al^Citation6^l
Tipifarnib	II	Recurrent GBM (67)	3%–11%	6%-17%	Cloughsey et al^Citation62
Temsirolimus	II	Recurrent GBM (65)	0	8%	Galanis et al^Citation63
Temsirolimus	II	Recurrent GBM (43)	5%	2%	Chang et al^Citation64
Fenretide	II	Recurrent GBM (23)	0	0	Puduvalli et al^Citation65
Gossypol	II	Recurrent GBM (15)	13%	NR	Bushunow et al^Citation66
Sorafenib	II	Recurrent GBM (32)	3%	9%	Reardon et al^Citation67
Cetuximab, bevacizumab and irinotecan	II	Recurrent GBM (43)	26%	33%	Hasselbalch et al^Citation68
Hydroxyurea and imatinib	II	Recurrent GBM (33)	9%	27%	Reardon et al^Citation69
Bendamustine	II	Recurrent GBM (16)	0	6%	Chamberlain and Johnston^Citation7

Note: *Prior anti-vascular endothelial growth factor therapy not allowed.

Abbreviations: NR, not reported; GBM, glioblastoma multiforme; PFS6, progression-free survival at 6 months.

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