Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer

Alex Adjei, Ann Mauer, Laura Bruzek, Randolph Stuart Marks, Shauna Hillman, Susan Geyer, Lorelei J. Hanson, John J. Wright, Charles Erlichman, Scott H Kaufmann, Everett E. Vokes

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Purpose: This phase II study was undertaken to define the efficacy and pharmacodynamics of R115777, a farnesyl transferase inhibitor, in the first-line treatment of patients with advanced non-small-cell lung cancer. Patients and Methods: Forty-four patients with measurable stage IIIB (pleural effusion) or stage IV disease received 193 courses of treatment (median, 2.0; range, 1 to 22) with R115777 300 mg administered orally twice daily for 21 of every 28 days. Buccal mucosa samples and peripheral blood mononuclear cells (PBMCs) were collected before and after 8 days of treatment to evaluate inhibition of farnesyl transferase in vivo. Results: No objective complete or partial responses were documented. Seven patients (16%; 95% confidence interval [CI], 8% to 31%) had disease stabilization for greater than 6 months. Median survival was 7.7 months (95% CI, 6.5 to 10.5) and time to progression was 2.7 months (95% CI, 1.9 to 3.1). The most severe toxicity was neutropenia (9% grade 3, 7% grade 4) and the most common toxicities were anemia (50% grade 1 or 2, 5% grade 3) and anorexia (50% grade 1 or 2, 2% grade 3). Mild peripheral neuropathy occurred in 25% of patients. Evidence of farnesyl transferase inhibition was documented in 83% of patients. Conclusion: Single-agent R115777 was well tolerated in patients with advanced NSCLC, but demonstrated minimal clinical activity. Inhibition of farnesylation in vivo was consistently documented. On the basis of promising results of farnesyl transferase inhibitor combinations with standard chemotherapy agents, future studies of this agent in NSCLC should be in combination with systemic chemotherapy.

Original languageEnglish (US)
Pages (from-to)1760-1766
Number of pages7
JournalJournal of Clinical Oncology
Volume21
Issue number9
DOIs
StatePublished - May 1 2003

Fingerprint

tipifarnib
Transferases
Non-Small Cell Lung Carcinoma
Confidence Intervals
Prenylation
Drug Therapy
Mouth Mucosa
Anorexia
Peripheral Nervous System Diseases
Pleural Effusion
Neutropenia
Anemia
Blood Cells
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer. / Adjei, Alex; Mauer, Ann; Bruzek, Laura; Marks, Randolph Stuart; Hillman, Shauna; Geyer, Susan; Hanson, Lorelei J.; Wright, John J.; Erlichman, Charles; Kaufmann, Scott H; Vokes, Everett E.

In: Journal of Clinical Oncology, Vol. 21, No. 9, 01.05.2003, p. 1760-1766.

Research output: Contribution to journalArticle

Adjei, Alex ; Mauer, Ann ; Bruzek, Laura ; Marks, Randolph Stuart ; Hillman, Shauna ; Geyer, Susan ; Hanson, Lorelei J. ; Wright, John J. ; Erlichman, Charles ; Kaufmann, Scott H ; Vokes, Everett E. / Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 9. pp. 1760-1766.
@article{787442ff0815491190fbdef22de0f7b8,
title = "Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer",
abstract = "Purpose: This phase II study was undertaken to define the efficacy and pharmacodynamics of R115777, a farnesyl transferase inhibitor, in the first-line treatment of patients with advanced non-small-cell lung cancer. Patients and Methods: Forty-four patients with measurable stage IIIB (pleural effusion) or stage IV disease received 193 courses of treatment (median, 2.0; range, 1 to 22) with R115777 300 mg administered orally twice daily for 21 of every 28 days. Buccal mucosa samples and peripheral blood mononuclear cells (PBMCs) were collected before and after 8 days of treatment to evaluate inhibition of farnesyl transferase in vivo. Results: No objective complete or partial responses were documented. Seven patients (16{\%}; 95{\%} confidence interval [CI], 8{\%} to 31{\%}) had disease stabilization for greater than 6 months. Median survival was 7.7 months (95{\%} CI, 6.5 to 10.5) and time to progression was 2.7 months (95{\%} CI, 1.9 to 3.1). The most severe toxicity was neutropenia (9{\%} grade 3, 7{\%} grade 4) and the most common toxicities were anemia (50{\%} grade 1 or 2, 5{\%} grade 3) and anorexia (50{\%} grade 1 or 2, 2{\%} grade 3). Mild peripheral neuropathy occurred in 25{\%} of patients. Evidence of farnesyl transferase inhibition was documented in 83{\%} of patients. Conclusion: Single-agent R115777 was well tolerated in patients with advanced NSCLC, but demonstrated minimal clinical activity. Inhibition of farnesylation in vivo was consistently documented. On the basis of promising results of farnesyl transferase inhibitor combinations with standard chemotherapy agents, future studies of this agent in NSCLC should be in combination with systemic chemotherapy.",
author = "Alex Adjei and Ann Mauer and Laura Bruzek and Marks, {Randolph Stuart} and Shauna Hillman and Susan Geyer and Hanson, {Lorelei J.} and Wright, {John J.} and Charles Erlichman and Kaufmann, {Scott H} and Vokes, {Everett E.}",
year = "2003",
month = "5",
day = "1",
doi = "10.1200/JCO.2003.09.075",
language = "English (US)",
volume = "21",
pages = "1760--1766",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "9",

}

TY - JOUR

T1 - Phase II study of the farnesyl transferase inhibitor R115777 in patients with advanced non-small-cell lung cancer

AU - Adjei, Alex

AU - Mauer, Ann

AU - Bruzek, Laura

AU - Marks, Randolph Stuart

AU - Hillman, Shauna

AU - Geyer, Susan

AU - Hanson, Lorelei J.

AU - Wright, John J.

AU - Erlichman, Charles

AU - Kaufmann, Scott H

AU - Vokes, Everett E.

PY - 2003/5/1

Y1 - 2003/5/1

N2 - Purpose: This phase II study was undertaken to define the efficacy and pharmacodynamics of R115777, a farnesyl transferase inhibitor, in the first-line treatment of patients with advanced non-small-cell lung cancer. Patients and Methods: Forty-four patients with measurable stage IIIB (pleural effusion) or stage IV disease received 193 courses of treatment (median, 2.0; range, 1 to 22) with R115777 300 mg administered orally twice daily for 21 of every 28 days. Buccal mucosa samples and peripheral blood mononuclear cells (PBMCs) were collected before and after 8 days of treatment to evaluate inhibition of farnesyl transferase in vivo. Results: No objective complete or partial responses were documented. Seven patients (16%; 95% confidence interval [CI], 8% to 31%) had disease stabilization for greater than 6 months. Median survival was 7.7 months (95% CI, 6.5 to 10.5) and time to progression was 2.7 months (95% CI, 1.9 to 3.1). The most severe toxicity was neutropenia (9% grade 3, 7% grade 4) and the most common toxicities were anemia (50% grade 1 or 2, 5% grade 3) and anorexia (50% grade 1 or 2, 2% grade 3). Mild peripheral neuropathy occurred in 25% of patients. Evidence of farnesyl transferase inhibition was documented in 83% of patients. Conclusion: Single-agent R115777 was well tolerated in patients with advanced NSCLC, but demonstrated minimal clinical activity. Inhibition of farnesylation in vivo was consistently documented. On the basis of promising results of farnesyl transferase inhibitor combinations with standard chemotherapy agents, future studies of this agent in NSCLC should be in combination with systemic chemotherapy.

AB - Purpose: This phase II study was undertaken to define the efficacy and pharmacodynamics of R115777, a farnesyl transferase inhibitor, in the first-line treatment of patients with advanced non-small-cell lung cancer. Patients and Methods: Forty-four patients with measurable stage IIIB (pleural effusion) or stage IV disease received 193 courses of treatment (median, 2.0; range, 1 to 22) with R115777 300 mg administered orally twice daily for 21 of every 28 days. Buccal mucosa samples and peripheral blood mononuclear cells (PBMCs) were collected before and after 8 days of treatment to evaluate inhibition of farnesyl transferase in vivo. Results: No objective complete or partial responses were documented. Seven patients (16%; 95% confidence interval [CI], 8% to 31%) had disease stabilization for greater than 6 months. Median survival was 7.7 months (95% CI, 6.5 to 10.5) and time to progression was 2.7 months (95% CI, 1.9 to 3.1). The most severe toxicity was neutropenia (9% grade 3, 7% grade 4) and the most common toxicities were anemia (50% grade 1 or 2, 5% grade 3) and anorexia (50% grade 1 or 2, 2% grade 3). Mild peripheral neuropathy occurred in 25% of patients. Evidence of farnesyl transferase inhibition was documented in 83% of patients. Conclusion: Single-agent R115777 was well tolerated in patients with advanced NSCLC, but demonstrated minimal clinical activity. Inhibition of farnesylation in vivo was consistently documented. On the basis of promising results of farnesyl transferase inhibitor combinations with standard chemotherapy agents, future studies of this agent in NSCLC should be in combination with systemic chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=0038362742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038362742&partnerID=8YFLogxK

U2 - 10.1200/JCO.2003.09.075

DO - 10.1200/JCO.2003.09.075

M3 - Article

VL - 21

SP - 1760

EP - 1766

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 9

ER -