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Multi-institutional phase 2 clinical and pharmacogenomic trial of tipifarnib plus etoposide for elderly adults with newly diagnosed acute myelogenous leukemia . Tipifarnib ( T ) exhibits modest activity in elderly adults with newly diagnosed acute myelogenous leukemia ( AML ) . Based on preclinical synergy , a phase 1 trial of T plus etoposide ( E ) yielded 25 % complete remission ( CR ) . We selected 2 comparable dose levels for a randomized phase 2 trial in 84 adults ( age range , 70-90 years ; median , 76 years ) who were not candidates for conventional chemotherapy . Arm A ( T 600 mg twice a day × 14 days , E 100 mg days 1-3 and 8-10 ) and arm B ( T 400 mg twice a day × 14 days , E 200 mg days 1-3 and 8-10 ) yielded similar CR , but arm B had greater toxicity . Total CR was 25 % , day 30 death rate 7 % . A 2-gene signature of high RASGRP1 and low aprataxin ( APTX ) expression previously predicted for T response . Assays using blasts from a subset of 40 patients treated with T plus E on this study showed that AMLs with a RASGRP1/APTX ratio of more than 5.2 had a 78 % CR rate and negative predictive value 87 % . This ratio did not correlate with outcome in 41 patients treated with conventional chemotherapies . The next T-based clinical trials will test the ability of the 2-gene signature to enrich for T responders prospectively . This study is registered at www.clinicaltrials.gov as # NCT00602771 .
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Intervention_Pharmacological
tipifarnib plus etoposide
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Participant_Age
elderly adults
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Participant_Condition
acute myelogenous leukemia
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Participant_Age
elderly adults
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Participant_Condition
AML
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Participant_Sample-size
84
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Participant_Age
adults
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Participant_Age
70-90 years
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Participant_Age
median , 76 years