2021
Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)
Leighl NB, Redman MW, Rizvi N, Hirsch FR, Mack PC, Schwartz LH, Wade JL, Irvin WJ, Reddy SC, Crawford J, Bradley JD, Stinchcombe TE, Ramalingam SS, Miao J, Minichiello K, Herbst RS, Papadimitrakopoulou VA, Kelly K, Gandara DR. Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760). Journal For ImmunoTherapy Of Cancer 2021, 9: e002973. PMID: 34429332, PMCID: PMC8386207, DOI: 10.1136/jitc-2021-002973.Peer-Reviewed Original ResearchConceptsDisease progressionAnti-programmed death ligand 1 therapyStage IV squamous cell lung cancerPrior anti-PD-1 therapyResponse rateAnti-PD-1 therapyDeath ligand 1 therapyMedian progression-free survivalSquamous cell lung cancerObjective response ratePhase II studyProgression-free survivalCell lung cancerSquamous lung carcinomaDurvalumab 1500Eligible patientsImmunotherapy combinationsPrimary endpointAdverse eventsII studyOverall survivalPartial responseTRIAL REGISTRATIONLung cancerLung carcinoma
2019
SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway–Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy)
Aggarwal C, Redman MW, Lara PN, Borghaei H, Hoffman P, Bradley JD, Newman AJ, Feldman MJ, Minichiello K, Miao J, Mack PC, Papadimitrakopoulou VA, Herbst RS, Kelly K, Gandara DR. SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway–Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy). Journal Of Thoracic Oncology 2019, 14: 1847-1852. PMID: 31195180, PMCID: PMC6901020, DOI: 10.1016/j.jtho.2019.05.041.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntineoplastic AgentsBenzamidesBiomarkers, TumorCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellFemaleFollow-Up StudiesGene AmplificationHumansLung NeoplasmsMaleMiddle AgedNeoplasm StagingPiperazinesPyrazolesReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 3Salvage TherapySurvival RateConceptsProgression-free survivalFGFR3 S249CFGFR alterationsOverall survivalPartial responseFGFR1 amplificationLung-MAPGrade 3 adverse eventsMedian progression-free survivalPlatinum-based systemic therapySolid Tumors version 1.1Squamous cell lung cancerMedian age 66 yearsFibroblast growth factor receptor inhibitorGrowth factor receptor inhibitorsFirst phase II trialGrade 4 sepsisResponse-evaluable patientsSquamous cell NSCLCUnconfirmed partial responsePhase II studyAcceptable safety profilePhase II trialResponse Evaluation CriteriaAge 66 years
2017
A multicohort phase I study of ramucirumab (R) plus pembrolizumab (P): Interim safety and clinical activity in patients with urothelial carcinoma.
Petrylak D, Arkenau H, Perez-Gracia J, Krebs M, Santana-Davila R, Yang J, Rege J, Mi G, Ferry D, Herbst R. A multicohort phase I study of ramucirumab (R) plus pembrolizumab (P): Interim safety and clinical activity in patients with urothelial carcinoma. Journal Of Clinical Oncology 2017, 35: 349-349. DOI: 10.1200/jco.2017.35.6_suppl.349.Peer-Reviewed Original ResearchTreatment-related AEsECOG PS 0Median durationPS 0PD-L1Urothelial carcinomaDay 1Phase 1a/b trialPlatinum-based systemic therapyTreatment-related grade 4Advanced urothelial carcinomaElevated alanine aminotransferaseNew safety signalsElevated aspartate aminotransferaseBaseline tumor tissuePreliminary efficacy dataTransitional cell carcinomaEligible ptsMeasurable diseaseMedian PFSStable diseasePartial responseProgressive diseaseSystemic therapyMedian age
2012
Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist
Subbiah V, Brown RE, Buryanek J, Trent J, Ashkenazi A, Herbst R, Kurzrock R. Targeting the Apoptotic Pathway in Chondrosarcoma Using Recombinant Human Apo2L/TRAIL (Dulanermin), a Dual Proapoptotic Receptor (DR4/DR5) Agonist. Molecular Cancer Therapeutics 2012, 11: 2541-2546. PMID: 22914439, PMCID: PMC3496030, DOI: 10.1158/1535-7163.mct-12-0358.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisBone NeoplasmsCell SurvivalChondrosarcomaDNA Mutational AnalysisHumansImmunohistochemistryIsocitrate DehydrogenaseLung NeoplasmsMaleMiddle AgedProteomicsProto-Oncogene Proteins c-bcl-2Radiography, ThoracicReceptors, Death DomainRecombinant ProteinsSignal TransductionTNF-Related Apoptosis-Inducing LigandTomography, X-Ray ComputedTreatment OutcomeConceptsRecombinant human Apo2L/TRAILApo2L/TRAILRecent computed tomography scanSustained partial responseEvidence of diseaseComputed tomography scanP-ERK 1/2Partial responseProgressive diseaseNF-κBp65Receptor agonistTomography scanSubcentimeter nodulesPatient tumorsMetastatic chondrosarcomaP-mTORPatientsProlonged responseP-STAT3Proapoptotic receptor agonistsChondrosarcomaBcl-2DulanerminLungTumorsPhase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours
Martin LP, Kozloff MF, Herbst RS, Samuel TA, Kim S, Rosbrook B, Tortorici M, Chen Y, Tarazi J, Olszanski AJ, Rado T, Starr A, Cohen RB. Phase I study of axitinib combined with paclitaxel, docetaxel or capecitabine in patients with advanced solid tumours. British Journal Of Cancer 2012, 107: 1268-1276. PMID: 22996612, PMCID: PMC3494424, DOI: 10.1038/bjc.2012.407.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsCommon treatment-related adverse eventsSolid tumorsTreatment-related adverse eventsAntitumour activitySelective second-generation inhibitorPhase ICo-administered agentsVascular endothelial growth factor receptorHand-foot syndromeEndothelial growth factor receptorHuman xenograft tumor modelsEfficacy of chemotherapyXenograft tumor modelMultiple tumor typesAxitinib pharmacokineticsCapecitabine pharmacokineticsGrowth factor receptorStable diseaseStarting doseAdverse eventsPartial responseComplete responseTreatment regimenDocetaxel exposure
2010
A First-in-Human Study of Conatumumab in Adult Patients with Advanced Solid Tumors
Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L, Juan G, Hwang YC, Wong S, Hill JS, Friberg G, LoRusso PM. A First-in-Human Study of Conatumumab in Adult Patients with Advanced Solid Tumors. Clinical Cancer Research 2010, 16: 5883-5891. PMID: 20947515, DOI: 10.1158/1078-0432.ccr-10-0631.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerAdvanced solid tumorsPartial responseColorectal cancerStable diseaseSolid tumorsPositron emission tomographic scansHuman death receptor 5Dose-expansion phaseGrade 3 eventsDose-escalation phaseCell lung cancerStandardized uptake valueHuman monoclonal agonist antibodyMonoclonal agonist antibodyDeath receptor 5Week 96Adult patientsAdverse eventsIntravenous dosesMore dosesTumor sizeLung cancerTumor levelsTumor response
2009
Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors
Herbst RS, Hong D, Chap L, Kurzrock R, Jackson E, Silverman JM, Rasmussen E, Sun YN, Zhong D, Hwang YC, Evelhoch JL, Oliner JD, Le N, Rosen LS. Safety, Pharmacokinetics, and Antitumor Activity of AMG 386, a Selective Angiopoietin Inhibitor, in Adult Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2009, 27: 3557-3565. PMID: 19546406, DOI: 10.1200/jco.2008.19.6683.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAngiogenesis InhibitorsAngiopoietinsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntimetabolites, AntineoplasticBevacizumabDose-Response Relationship, DrugDrug-Related Side Effects and Adverse ReactionsFatigueFemaleHumansInfusions, IntravenousMaleMaximum Tolerated DoseMiddle AgedNeoplasm StagingNeoplasmsTreatment OutcomeConceptsAMG 386Advanced solid tumorsPartial responseAntitumor activitySolid tumorsElimination half-life valuesPatients 48 hoursMaximum-tolerated doseTreatment-related toxicityDose-limiting toxicityRefractory ovarian cancerWeeks of treatmentPeptide-Fc fusion proteinVolume transfer constantAngiopoietin inhibitorsCommon toxicitiesStable diseasePeripheral edemaAdult patientsClinical sequelaeMethods PatientsWeekly dosesTumor burdenRespiratory arrestSafety profileS0536: Carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC): A SWOG phase II study
Gandara D, Kim E, Herbst R, Moon J, Redman M, Dakhil S, Hirsch F, Mack P, Franklin W, Kelly K. S0536: Carboplatin, paclitaxel, cetuximab, and bevacizumab followed by cetuximab and bevacizumab maintenance in advanced non-small cell lung cancer (NSCLC): A SWOG phase II study. Journal Of Clinical Oncology 2009, 27: 8015-8015. DOI: 10.1200/jco.2009.27.15_suppl.8015.Peer-Reviewed Original ResearchNon-small cell lung cancerAdvanced non-small cell lung cancerProgression-free survivalOverall survivalEGFR FISHStable diseasePartial responseNon-squamous cell non-small cell lung cancerDay 1Median age 64 yearsTreatment-related deathsDisease control ratePhase II studyPhase III trialsPlatinum-based chemotherapyAge 64 yearsCell lung cancerEfficacy of carboplatinActive regimenAUC 6Bevacizumab maintenanceEligible ptsMedian followBrain metastasesEfficacy outcomesA phase 2 study of cetuximab in combination with docetaxel in chemotherapy‐refractory/resistant patients with advanced nonsmall cell lung cancer
Kim ES, Mauer AM, William WN, Tran HT, Liu D, Lee JJ, Windt P, Hong WK, Vokes EE, Herbst RS. A phase 2 study of cetuximab in combination with docetaxel in chemotherapy‐refractory/resistant patients with advanced nonsmall cell lung cancer. Cancer 2009, 115: 1713-1722. PMID: 19208430, PMCID: PMC5142442, DOI: 10.1002/cncr.24148.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCetuximabDisease ProgressionDocetaxelDrug Administration ScheduleErbB ReceptorsFemaleHumansLung NeoplasmsMaleMiddle AgedNeoplasm Recurrence, LocalTaxoidsConceptsNonsmall cell lung cancerAdvanced nonsmall cell lung cancerResponse rateOverall survivalResistant patientsLung cancerEpidermal growth factor receptor expressionCommon grade 3Growth factor receptor expressionMedian overall survivalSecond-line settingPhase 2 studyCell lung cancerTarget sample sizeFactor receptor expressionStable diseaseAdverse eventsPartial responseComplete responseDisease recurrenceMedian timeDisease progressionReceptor expressionAllergic reactionsGrade 3
2007
First-in-human study of AMG 655, a pro-apoptotic TRAIL receptor-2 agonist, in adult patients with advanced solid tumors
LoRusso P, Hong D, Heath E, Kurzrock R, Wang D, Hsu M, Goyal L, Wiezorek J, Storgard C, Herbst R. First-in-human study of AMG 655, a pro-apoptotic TRAIL receptor-2 agonist, in adult patients with advanced solid tumors. Journal Of Clinical Oncology 2007, 25: 3534-3534. DOI: 10.1200/jco.2007.25.18_suppl.3534.Peer-Reviewed Original ResearchNon-small cell lung cancerMetabolic partial responseAdvanced solid tumorsPartial responseStable diseaseColorectal cancerHuman studiesSolid tumorsMaximum standardized uptake valueDose-linear kineticsElevated serum lipaseSequential dose cohortsOnly grade 3Cell lung cancerReceptor 2 agonistStandardized uptake valueHuman monoclonal agonist antibodyMonoclonal agonist antibodyAnti-tumor activitySensitive tumor cellsTumor response dataSerious AEsDose cohortsProgressive diseaseUnacceptable toxicityPhase II study of the efficacy and safety of intravenous (IV) AVE0005 (VEGF Trap) given every 2 weeks in patients (Pts) with platinum- and erlotinib- resistant adenocarcinoma of the lung (NSCLA)
Massarelli E, Miller V, Leighl N, Rosen P, Albain K, Hart L, Melnyk O, Sternas L, Ackerman J, Herbst R. Phase II study of the efficacy and safety of intravenous (IV) AVE0005 (VEGF Trap) given every 2 weeks in patients (Pts) with platinum- and erlotinib- resistant adenocarcinoma of the lung (NSCLA). Journal Of Clinical Oncology 2007, 25: 7627-7627. DOI: 10.1200/jco.2007.25.18_suppl.7627.Peer-Reviewed Original ResearchTreatment-emergent adverse eventsPartial responsePerformance statusGrade 3Prior treatmentSquamous cell lung cancerEmergent adverse eventsSignificant bleeding diathesisECOG performance statusObjective response ratePhase II studyProgression-free survivalSingle-agent activityDuration of responseMulti-center trialMost common reasonsInterim futility analysisVEGF receptor inhibitorQuality of lifeBone painEvaluable ptsFebrile neutropeniaMeasurable diseaseBrain metastasesAdverse eventsSafety, Pharmacokinetics, and Efficacy of AMG 706, an Oral Multikinase Inhibitor, in Patients With Advanced Solid Tumors
Rosen LS, Kurzrock R, Mulay M, Van Vugt A, Purdom M, Ng C, Silverman J, Koutsoukos A, Sun YN, Bass MB, Xu RY, Polverino A, Wiezorek JS, Chang DD, Benjamin R, Herbst RS. Safety, Pharmacokinetics, and Efficacy of AMG 706, an Oral Multikinase Inhibitor, in Patients With Advanced Solid Tumors. Journal Of Clinical Oncology 2007, 25: 2369-2376. PMID: 17557949, DOI: 10.1200/jco.2006.07.8170.Peer-Reviewed Original ResearchConceptsMaximum-tolerated doseAMG 706Advanced solid tumorsSolid tumorsAdvanced refractory solid tumorsRefractory advanced solid tumorsVascular endothelial growth factor receptor 1Frequent adverse eventsRefractory solid tumorsDose-proportional mannerFactor receptorDose-finding studyOral multikinase inhibitorStudy of patientsPlacental growth factorGrowth factor receptor 1Platelet-derived growth factor receptorFactor receptor 1Stem cell factor receptorGrowth factor receptorStable diseaseKinase domain receptorAdverse eventsPartial responseProgressive disease
2006
A phase I safety and pharmacokinetic (PK) study of recombinant Apo2L/TRAIL, an apoptosis-inducing protein in patients with advanced cancer
Herbst R, Mendolson D, Ebbinghaus S, Gordon M, O’Dwyer P, Lieberman G, Ing J, Kurzrock R, Novotny W, Eckhardt G. A phase I safety and pharmacokinetic (PK) study of recombinant Apo2L/TRAIL, an apoptosis-inducing protein in patients with advanced cancer. Journal Of Clinical Oncology 2006, 24: 3013-3013. DOI: 10.1200/jco.2006.24.18_suppl.3013.Peer-Reviewed Original ResearchAdvanced solid tumorsLiver metastasesSolid tumorsHematologic malignanciesApo2L/TRAILRecombinant human Apo2L/TRAILPost-baseline tumour assessmentPhase I safetyObjective partial responseFurther dose optimizationAttributable toxicityStable diseaseAdult patientsI safetyPartial responseAdvanced cancerCommon diagnosisRandomized trialsStandard treatmentReceptor agonistOvarian cancerPreclinical modelsSafety dataTumor assessmentMost normal cellsSafety and antitumor activity of AMG 706 in patients (pts) with thyroid cancer (TC): A subset analysis from a phase 1 dose-finding study
Boughton D, Rosen L, Van Vugt A, Kurzrock R, Eschenberg M, Wiezorek J, Ingram M, Wang D, Stepan D, Herbst R. Safety and antitumor activity of AMG 706 in patients (pts) with thyroid cancer (TC): A subset analysis from a phase 1 dose-finding study. Journal Of Clinical Oncology 2006, 24: 3030-3030. DOI: 10.1200/jco.2006.24.18_suppl.3030.Peer-Reviewed Original ResearchAMG 706Partial responseThyroid cancerStable diseaseAntitumor activityPhase 1 dose-finding studyTreatment-related adverse eventsPhase 2 studyRefractory solid tumorsStage IV diseasePhase 1 studySmall-molecule multi-kinase inhibitorAdvanced thyroid cancerMedullary thyroid cancerDose-finding studyDirect antitumor activityMulti-kinase inhibitorECOG 1Baseline demographicsObjective responseProgressive diseaseAdverse eventsMedian ageMedian timeConfirmation of responseEGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma (BAC): Results of a prospective phase II trial
Miller V, Zakowski M, Riely G, Pao W, Ladanyi M, Tsao A, Sandler A, Herbst R, Kris M, Johnson D. EGFR mutation and copy number, EGFR protein expression and KRAS mutation as predictors of outcome with erlotinib in bronchioloalveolar cell carcinoma (BAC): Results of a prospective phase II trial. Journal Of Clinical Oncology 2006, 24: 7003-7003. DOI: 10.1200/jco.2006.24.18_suppl.7003.Peer-Reviewed Original ResearchManaging cutaneous side effects associated with erlotinib in head and neck cancer (HNC) and non-small cell lung cancer (NSCLC) patients (pts)
Oishi K, Garey J, Burke B, Herbst R, Kim E. Managing cutaneous side effects associated with erlotinib in head and neck cancer (HNC) and non-small cell lung cancer (NSCLC) patients (pts). Journal Of Clinical Oncology 2006, 24: 18538-18538. DOI: 10.1200/jco.2006.24.18_suppl.18538.Peer-Reviewed Original ResearchGrade 1 rashPartial responseGrade 2Epidermal growth factor receptorGrade 3NSCLC ptsDose modificationComplete responseTreatment algorithmTreatment responseSide effectsNon-small cell lung cancer patientsGrade 1Cell lung cancer patientsPrior chemotherapy regimenPhase II studyCutaneous side effectsLung cancer patientsGrade 4Acneiform rashChemotherapy regimenDose delaysGrowth factor receptorII studyCutaneous toxicityAsian Ethnicity as a Predictor of Response in Patients with Non–Small-Cell Lung Cancer Treated with Gefitinib on an Expanded Access Program
Thomas SK, Fossella FV, Liu D, Schaerer R, Tsao AS, Kies MS, Pisters KM, Blumenschein GR, Glisson BS, Lee JJ, Herbst RS, Zinner RG. Asian Ethnicity as a Predictor of Response in Patients with Non–Small-Cell Lung Cancer Treated with Gefitinib on an Expanded Access Program. Clinical Lung Cancer 2006, 7: 326-331. PMID: 16640804, DOI: 10.3816/clc.2006.n.014.Peer-Reviewed Original ResearchConceptsExpanded Access ProgramCell lung cancerLung cancerAsian ethnicityD. Anderson Cancer CenterPartial response rateStable disease rateAdvanced-stage NSCLCPredictors of responseAccess programAnderson Cancer CenterEast Asian ethnicityChart reviewMedian survivalPartial responseIndependent predictorsMedian timeSmoking statusRetrospective studyCancer CenterPatientsResponse rateSurvival rateMultivariate analysisGefitinib
2005
Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results
Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD, Freddo JL, Wilding G. Phase I Trial of the Oral Antiangiogenesis Agent AG-013736 in Patients With Advanced Solid Tumors: Pharmacokinetic and Clinical Results. Journal Of Clinical Oncology 2005, 23: 5474-5483. PMID: 16027439, DOI: 10.1200/jco.2005.04.192.Peer-Reviewed Original ResearchConceptsAdvanced solid tumorsAG-013736Clinical activityOral receptor tyrosine kinase inhibitorSolid tumorsReceptor tyrosine kinase inhibitorsGrowth factorSingle test dosesMaximum-tolerated dosePhase II doseDose-limiting toxicitySignificant drug interactionsPeak plasma concentrationEndothelial cell growth factorPhase II testingVascular endothelial cell growth factorTyrosine kinase inhibitorsHighest dose levelPlatelet-derived growth factorIndividual PK parametersEffect of foodCell growth factorObserved hypertensionDrug holidayPartial response
2004
Clinical and pharmacokinetic study of TNP-470, an angiogenesis inhibitor, in combination with paclitaxel and carboplatin in patients with solid tumors
Tran HT, Blumenschein GR, Lu C, Meyers CA, Papadimitrakopoulou V, Fossella FV, Zinner R, Madden T, Smythe LG, Puduvalli VK, Munden R, Truong M, Herbst RS. Clinical and pharmacokinetic study of TNP-470, an angiogenesis inhibitor, in combination with paclitaxel and carboplatin in patients with solid tumors. Cancer Chemotherapy And Pharmacology 2004, 54: 308-314. PMID: 15184994, DOI: 10.1007/s00280-004-0816-z.Peer-Reviewed Original ResearchConceptsPharmacokinetics of carboplatinTNP-470Solid tumorsDoublet regimenAngiogenesis inhibitor TNP-470Hematological toxic effectsRegimen of paclitaxelCycles of therapyMedian survival durationCombination of paclitaxelPatient survival ratesRecent clinical trialsHead/neckCell lung carcinomaTNP-470 administrationToxic effectsAUC 5AUC 6Chemotherapy doubletsIntravenous paclitaxelPurposePreclinical studiesStable diseasePartial responseRandomized studySurvival durationPhase I Study of the Farnesyltransferase Inhibitor Lonafarnib with Paclitaxel in Solid Tumors
Khuri FR, Glisson BS, Kim ES, Statkevich P, Thall PF, Meyers ML, Herbst RS, Munden RF, Tendler C, Zhu Y, Bangert S, Thompson E, Lu C, Wang XM, Shin DM, Kies MS, Papadimitrakopoulou V, Fossella FV, Kirschmeier P, Bishop WR, Hong WK. Phase I Study of the Farnesyltransferase Inhibitor Lonafarnib with Paclitaxel in Solid Tumors. Clinical Cancer Research 2004, 10: 2968-2976. PMID: 15131032, DOI: 10.1158/1078-0432.ccr-03-0412.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerGrade 4 diarrheaCell lung cancerPartial responseLung cancerMetastatic non-small cell lung cancerSolid tumorsGrade 3 peripheral neuropathyPrincipal grade 3/4 toxicitiesDose level 3Durable partial responseGrade 3 hyperbilirubinemiaPrevious taxane therapyGrade 3/4 toxicitiesGrade 4 neutropeniaPhase II trialDose-limiting toxicityPhase I trialFarnesyltransferase inhibitor lonafarnibNovel farnesyltransferase inhibitorPlasma paclitaxelII trialTaxane therapyCombination regimenMedian duration