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

Heymach, John V.; Johnson, David H.; Khuri, Fadlo R.; Safran, Howard; Schlabach, Larry; Yunus, Furhan; DeVore, Ronald A.; Porre, P. M. De; Richards, Henry; Jia, Xiaoyu; Zhang, S.; Johnson, Bruce E.

doi:10.1093/annonc/mdh315

Cited by 85 publications

(40 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…R115777 was administered in 3-week cycles at a dose of 400 mg orally twice daily for 14 consecutive days followed by seven days off treatment, and 22 patients were enrolled. The trial was terminated as no objective responses were observed in the 20 patients evaluable for response (59). was closely associated with the induction of immunological response to vaccination.…”

Section: Other Agentsmentioning

confidence: 99%

Targeted therapies in small cell lung cancer (Review)

Wang

Mao

2012

Oncol Lett

View full text Add to dashboard Cite

Abstract. Lung cancer is the leading cause of cancer-related mortality. Small cell lung cancer (SCLC) accounted for 12.95% of all lung cancer histological types in 2002. Despite trends toward modest improvement in survival, the outcome remains extremely poor. Chemotherapy is the cornerstone of treatment in SCLC. More than two-thirds of patients who succumb to lung cancer in the United States are over 65 years old. Elderly patients tolerate chemotherapy poorly and need novel therapeutic agents. Targeted drugs have less toxicity than chemotherapy drugs, but no targeted agents have been approved for use in the treatment of SCLC patients to date. Certain new targeted agents, including gefitinib, bevacizumab and Bcl-2 inhibitors, offer a promise of improved outcomes, however negative results are more commonly reported than positive. This review focuses on targeted therapies in SCLC.

show abstract

Section: Other Agentsmentioning

confidence: 99%

Targeted therapies in small cell lung cancer (Review)

Wang

Mao

2012

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…More recent phase II studies explored higher dosages with strict dose-reduction rules for toxicity. In one study, patients with relapsed small-cell lung cancer received 400 mg twice daily for 14 consecutive days followed by 1 week of rest, and no objective responses and only one case of stable disease were observed [86]. To date, the most promising activity of tipifarnib was reported in patients with untreated poor-risk acute myeloid leukemia or myelodysplastic syndrome (MDS), in which a 33% response rate (eight complete responses, two partial responses) was seen [87].…”

Section: Tipifarnibmentioning

confidence: 99%

Development of Farnesyl Transferase Inhibitors: A Review

2005

View full text Add to dashboard Cite

Learning Objectives After completing this course, the reader will be able to: Describe the potential mechanisms by which farnesyl transferases inhibit tumor growth. Explain possible mechanisms by which tumor cells may develop resistance to this class of agents. Discuss the scientific requirements for developing targeted cancer treatments that will actually be useful in patients. Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at http://CME.TheOncologist.com

show abstract

“…Farnesyl transferase inhibitors have shown efficacy in preclinical models of SCLC, presumably through effects on the large number of farnesylated second messengers that regulate growth and survival [30]. This observation has not yet successfully translated into the clinic; in an initial phase II clinical trial of 22 patients with relapsed SCLC, the farnesyl transferase inhibitor tipifarnib (Zarnestra ™ , R115777) failed to show clinical activity as a single agent [31].…”

Section: Farnesylation and Receptor-associated Second Messengersmentioning

confidence: 99%

Fast, hungry and unstable: finding the Achilles’ heel of small-cell lung cancer

Hann

Rudin

2007

Trends in Molecular Medicine

View full text Add to dashboard Cite

Over 95% of patients with small-cell lung cancer (SCLC) die within five years of diagnosis. The standard of care and the dismal prognosis for this disease have not changed significantly over the past 25 years. Some of the characteristics of SCLC that have defined it as a particularly virulent form of cancer -rapid proliferation, excessive metabolic and angiogenic dependence, apoptotic imbalance and genetic instability -are now being pursued as tumor-specific targets for intervention both in preclinical and early phase clinical studies. Here, we summarize areas of ongoing anti-cancer drug development, including classes of agents that target essential pathways regulating proliferation, angiogenesis, apoptotic resistance, chromosomal and protein stability, and cell-cell and cell-matrix interaction.

show abstract

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

Abstract: R115777 showed no significant antitumor activity as a single agent in sensitive-relapse SCLC.

Cited by 85 publications

References 25 publications

Targeted therapies in small cell lung cancer (Review)

Targeted therapies in small cell lung cancer (Review)

Development of Farnesyl Transferase Inhibitors: A Review

Fast, hungry and unstable: finding the Achilles’ heel of small-cell lung cancer

Contact Info

Product

Resources

About