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Phase II study of the farnesyl transferase inhibitor R115777 in patients with sensitive relapse small-cell lung
J V Heymach1, D H Johnson, F R Khuri
1Dana Farber Cancer Institute and Massachusetts General Hospital, Boston, MA 02115, USA.
Background:
R115777 (tipifarnib, Zarnestra) is a farnesyl transferase inhibitor that blocks the farnesylation of proteins involved in signal transduction pathways critical for cell proliferation and survival. This multicenter phase II study was conducted to determine the efficacy, tolerability and pharmacokinetics of R115777 in patients with relapsed small-cell lung cancer (SCLC).
Patients And Methods:
Patients who had a partial or complete response to their initial chemotherapy regimen, followed by at least 3 months off treatment before relapse (sensitive relapse) were eligible. R115777 was administered in 3-week cycles at a dose of 400 mg orally twice daily for 14 consecutive days followed by 7 days off treatment.
Results:
Twenty-two patients were enrolled. The median progression-free survival was 1.4 months and median overall survival was 6.8 months. Non-hematological toxicities were predominantly grade 1-2 and included nausea (64%) and fatigue (60%). Grade 3-4 granulocytopenia and thrombocytopenia occurred in 27% and 23% of patients, respectively. Febrile neutropenia was not observed. Pharmacokinetic studies demonstrated peak plasma concentrations of R115777 2.6-4.5 h after oral dosing and no significant drug accumulation. The trial was terminated because no objective responses were observed in 20 patients evaluable for response.
Conclusions:
R115777 showed no significant antitumor activity as a single agent in sensitive-relapse SCLC.
Insights
Tipifarnib (R115777) showed no significant antitumor activity in patients with relapsed small-cell lung cancer. This phase II trial found limited efficacy and manageable toxicities, leading to early termination due to lack of objective responses.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Tipifarnib (R115777) is a farnesyl transferase inhibitor targeting cell proliferation and survival pathways.
- This study investigated R115777 in patients with relapsed small-cell lung cancer (SCLC).
Purpose of the Study:
- To determine the efficacy, tolerability, and pharmacokinetics of R115777.
- To evaluate R115777 as a single agent in sensitive-relapse SCLC.
Main Methods:
- A multicenter phase II study enrolled 22 patients with sensitive-relapse SCLC.
- R115777 was administered orally at 400 mg twice daily for 14 days on/7 days off.
- Patients had previously responded to chemotherapy and relapsed after at least 3 months.
Main Results:
- Median progression-free survival was 1.4 months; median overall survival was 6.8 months.
- Common toxicities included nausea (64%) and fatigue (60%); grade 3-4 granulocytopenia (27%) and thrombocytopenia (23%) occurred.
- No objective responses were observed in 20 evaluable patients, leading to trial termination.
Conclusions:
- R115777 demonstrated no significant antitumor activity as a single agent in this patient population.
- The drug showed manageable toxicity but lacked clinical efficacy in sensitive-relapse SCLC.
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