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HIV protease inhibitor shows promise with concurrent chemoradiotherapy for non-small cell lung cancer
Nelfinavir mesylate administered with concurrent chemoradiotherapy appeared associated with promising responses and survival outcomes among patients with locally advanced non-small cell lung cancer, according to results of a prospective single-arm phase 1/phase 2 trial published in JAMA Oncology.
The combination also demonstrated acceptable toxicity.
“One approach to improve local tumor control [in NSCLC] is through concomitant administration of a radiosensitizing drug during standard radiotherapy,” Ramesh Rengan, MD, PhD, assistant professor in the department of radiation oncology at University of Washington School of Medicine, and colleagues wrote. “Preclinical studies have shown that a class of protease inhibitors used to treat HIV can radiosensitize tumor cells both in vitro and in vivo.”
Rengan and colleagues administered nelfinavir mesylate (Viracept, Pfizer), an oral protease inhibitor, to 35 patients (median age, 60 years; range, 39-79; 54% men) with stage IIIA or stage IIIB locally advanced NSCLC at a dose 1 level of 625 mg twice daily (n = 5) or a dose 2 level of 1,250 mg twice daily (n = 30) for 7 to 14 days before and during concurrent chemoradiotherapy.
Toxicity and the maximum tolerated dose served as phase 1 endpoints. OS, local failure, PFS and objective response rate served as phase 2 endpoints.
Median follow-up for all patients was 6.8 years and a minimum of 5 years for all survivors.
Results of the phase 1 portion showed no dose-limiting toxic effects.
Among 33 patients with evaluable post-treatment computed tomographic scans, researchers observed an ORR of 94% (95% CI, 86-100). Median PFS among these patients was 11.7 months (95% CI, 6.2-17.1) and median OS was 41.1 months (95% CI, 19-63.1). The mean OS rate at 5 years was 37.1%.
Cumulative incidence of local failure was 39% (95% CI, 30.5-47.5).
Two patients in the first dose level and 18 patients in the second dose level experienced grade 3 or grade 4 leukopenia, however, none required decreased doses of chemotherapy or nelfinavir mesylate.
The study’s nonrandomized nature and a lack of information on whether this approach will work in a larger, more heterogeneous group of patients served as its primary limitations.
“Compared with historical data of patients with this disease who received chemotherapy and radiation, our outcomes were favorable,” Rengan said in a press release. “We are certainly interested to pursue a randomized trial.” – by John DeRosier
Disclosures: Rengan reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.