A phase I trial of the HIV protease inhibitor nelfinavir with concurrent chemoradiotherapy for unresectable stage IIIA/IIIB non-small cell lung cancer: a report of toxicities and clinical response

Ramesh Rengan, Rosemarie Mick, Daniel Pryma, Mark A Rosen, Lilie L Lin, Amit M Maity, Tracey L Evans, James P Stevenson, Corey J Langer, John Kucharczuk, Joseph Friedberg, Susan Prendergast, Tiffany Sharkoski, Stephen M Hahn

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68 Scopus citations

Abstract

BACKGROUND: The objective of this phase I trial was to determine dose-limiting toxicities (DLT) and the maximally tolerated dose of the radiosensitizer Nelfinavir in combination with concurrent chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC).

METHODS: Nelfinavir (dose level 1: 625 mg orally [PO] twice a day; dose level 2: 1250 mg PO twice a day) was administered for 7 to 14 days before and concurrently with concurrent chemoradiotherapy to patients with biopsy confirmed IIIA or IIIB unresectable NSCLC. Five patients were treated at dose level 1; eight patients were treated at dose level 2. Patients were treated with concurrent chemoradiotherapy to a dose of 66.6 Gy. DLTs were defined as any treatment-related grade 4 hematologic toxicity requiring a break in therapy or nonhematologic grade 3 or higher toxicity except esophagitis and pneumonitis.

RESULTS: Sixteen patients were enrolled and 13 patients received at least one dose of nelfinavir. Twelve patients were treated with nelfinavir and concurrent chemoradiotherapy. No DLTs have been observed at either dose level. The maximum tolerated dose of nelfinavir was therefore 1250 mg PO twice a day. Six patients experienced grade 4 leukopenia. One patient experienced grade 4 thromobcytopenia. Median follow-up for all 12 response-evaluable patients was 31.6 months and for survivors is 23.5 months. Nine of the 12 patients had evaluable posttreatment positron emission tomography/computed tomography with metabolic response as follows: overall response: 9/9 (100%); complete response: 5/9 (56%); and partial response: 4/9 (44%).

CONCLUSION: Nelfinavir administered with concurrent chemoradiotherapy is associated with acceptable toxicity in stage IIIA/IIIB NSCLC. The metabolic response and tumor response data suggest that nelfinavir has promising activity in this disease.

Original languageEnglish
Pages (from-to)709-15
Number of pages7
JournalJournal of Thoracic Oncology
Volume7
Issue number4
DOIs
StatePublished - Mar 2012

Keywords

  • Aged
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Female
  • Follow-Up Studies
  • HIV Protease Inhibitors/adverse effects
  • Humans
  • Lung Neoplasms/drug therapy
  • Male
  • Middle Aged
  • Nelfinavir/adverse effects
  • Neoplasm Staging
  • Phosphoinositide-3 Kinase Inhibitors
  • Tomography, X-Ray Computed

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