Efficacy of nelfinavir as monotherapy in refractory adenoid cystic carcinoma: Results of a phase II clinical trial

Abstract

Background Adenoid cystic carcinoma (ACCs) are malignant salivary gland tumors noteworthy for high rates of late failure with limited salvage therapy options. We have previously shown increased Akt signaling is common in ACC and the HIV protease inhibitor nelfinavir (NFV) inhibits in vitro tumor growth by suppressing Akt signaling. This phase II trial was conducted to determine progression free survival in response to NFV in patients with recurrent/end stage ACC who have failed standard therapies. Methods Eligible patients had recurrent or end stage ACC and measureable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria. NFV was provided at 1250 mg twice daily. Results Among 15 trial participants, median progression free survival was 5.5 months (lower 95% bound 4.4 months). No patient achieved a RECIST partial or complete response to therapy. Conclusion NFV monotherapy does not result in a meaningful improvement in clinical outcomes among patients with recurrent ACC.

HIV‐protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO‐hybridized derivatives?

“…Thirty‐six % of subjects had stable disease for >6 months . In another study, no efficacy was observed in 15 patients with adenoid cystic carcinomas . The median progression‐free survival was 5.5 months and no patient achieved a partial or complete response.…”

New Developments in Salivary Gland Pathology: Clinically Useful Ancillary Testing and New Potentially Targetable Molecular Alterations

“…Nelfinavir, an antiretroviral drug approved for use in HIV treatment, is thought to exhibit inhibition of the Akt signaling pathway and has shown promise as cancer monotherapy in preclinical studies. 116 Hoover et al 116 conducted a phase II clinical trial with nelfinavir in patients with advanced AdCC but no objective responses were observed. Table 2 summarizes studies of targeted therapy in AdCC.…”

HIV‐1, HAART and cancer: A complex relationship

“…No meaningful improvement in clinical outcomes was reported among patients with recurrent adenoid cystic carcinomas and nelfinavir (PI) monotherapy in a phase II clinical trial. 191 The use of efavirenz (NNRTI) also did not improve the nonprogression rate of castration-resistant prostate cancer in a phase II clinical trial. 192 A phase II clinical trial of ritonavir/lopinavir (PIs) combination in patients with progressive or recurrent high-grade gliomas did not reveal a potent clinical activity either.…”