2022
Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors
Lee M, Wong A, Ow S, Sundar R, Tan D, Soo R, Chee C, Lim J, Yong W, Lim S, Goh B, Wang L, Lee S. Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors. Targeted Oncology 2022, 17: 141-151. PMID: 35195837, PMCID: PMC8995271, DOI: 10.1007/s11523-022-00867-0.Peer-Reviewed Original ResearchConceptsHER2+ metastatic breast cancerDose-limiting toxicityMetastatic breast cancerBreast cancerSubcutaneous trastuzumabSolid tumorsConclusionsThe recommended phase II dosePharmacokinetic analysisRecommended phase II doseHER2+ breast cancerAdvanced solid tumorsPalliative systemic therapyMetastatic solid tumorsResultsThirty-seven patientsArea under the curveWeekly paclitaxelNeoadjuvant therapyStable diseaseFebrile neutropeniaPartial responseSystemic therapyMethodsEligible patientsEfficacy signalsElectrolyte disturbancesBiliary tract
2018
Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer
Basu B, Krebs M, Sundar R, Wilson R, Spicer J, Jones R, Brada M, Talbot D, Steele N, Garces A, Brugger W, Harrington E, Evans J, Hall E, Tovey H, de Oliveira F, Carreira S, Swales K, Ruddle R, Raynaud F, Purchase B, Dawes J, Parmar M, Turner A, Tunariu N, Banerjee S, de Bono J, Banerji U. Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high-grade serous ovarian and squamous non-small-cell lung cancer. Annals Of Oncology 2018, 29: 1918-1925. PMID: 30016392, PMCID: PMC6158767, DOI: 10.1093/annonc/mdy245.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBenzamidesCarcinoma, Non-Small-Cell LungDrug Administration ScheduleFemaleHumansLung NeoplasmsMaleMaximum Tolerated DoseMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Middle AgedMorpholinesOvarian NeoplasmsPaclitaxelPhosphorylationProtein Kinase InhibitorsPyrimidinesResponse Evaluation Criteria in Solid TumorsRibosomal Protein S6 KinasesConceptsHigh-grade serous ovarian cancerSquamous non-small-cell lung cancerNon-small-cell lung cancerWeekly paclitaxelOvarian cancerSchedule ALung cancerIntermittent scheduleRecommended phase II doseResponse rateDose-escalated armPhase II doseRECIST response rateDose-limiting toxicityProgression-free survivalAdvanced solid tumorsPhase I trialSerous ovarian cancerResistance to chemotherapyP-S6K levelsConsecutive daysII doseDose escalationExpansion cohortI trial
2017
TAX-TORC: A phase I trial of vistusertib (AZD2014) in combination with weekly paclitaxel with integrated pharmacodynamic (PD) and molecular characterization (MC) studies.
Sundar R, Basu B, Wilson R, Spicer J, Jones R, Krebs M, Brada M, Talbot D, Steele N, Hall E, Tovey H, Carreira S, de Oliveira F, Swales K, Balarajah G, Dawes J, Parmar M, De Bono J, Banerji U. TAX-TORC: A phase I trial of vistusertib (AZD2014) in combination with weekly paclitaxel with integrated pharmacodynamic (PD) and molecular characterization (MC) studies. Journal Of Clinical Oncology 2017, 35: 2571-2571. DOI: 10.1200/jco.2017.35.15_suppl.2571.Peer-Reviewed Original ResearchHigh-grade serous ovarian cancerHigh-grade serous ovarian cancer patientsRecommended phase 2 doseMedian progression free survivalImproving outcomes of patientsPhase 2 doseDose-limiting toxicityDose-escalation partProgression free survivalArchival tumor tissuePhase I trialSerous ovarian cancerOutcomes of patientsLines of treatmentResistance to chemotherapyP-S6K levelsPre-dose levelsPlatelet-rich plasmaWeekly paclitaxelExpansion cohortFree survivalPlatinum therapyATM mutationsLimiting toxicitiesBID POLimb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study
Sundar R, Bandla A, Tan S, Liao L, Kumarakulasinghe N, Jeyasekharan A, Ow S, Ho J, Tan D, Lim J, Vijayan J, Therimadasamy A, Hairom Z, Ang E, Ang S, Thakor N, Lee S, Wilder-Smith E. Limb Hypothermia for Preventing Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients: A Pilot Study. Frontiers In Oncology 2017, 6: 274. PMID: 28119855, PMCID: PMC5222823, DOI: 10.3389/fonc.2016.00274.Peer-Reviewed Original ResearchNerve conduction studiesBreast cancer patientsPeripheral neuropathyPaclitaxel infusionLimb hypothermiaPreventing paclitaxel-induced peripheral neuropathyCancer patientsPaclitaxel-induced peripheral neuropathyHistory of diabetes mellitusDose-limiting toxicityCompound muscle action potentialCool limbsMuscle action potentialWeekly paclitaxelSensory velocityDiabetes mellitusGrade 2Contralateral limbAction potentialsPaclitaxelPilot trialPatientsControl limbsHypothermiaTolerance to hypothermia
2016
Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy
Sundar R, Jeyasekharan A, Pang B, Soong R, Kumarakulasinghe N, Ow S, Ho J, Lim J, Tan D, Wilder-Smith E, Bandla A, Tan S, Asuncion B, Fazreen Z, Hoppe M, Putti T, Poh L, Goh B, Lee S. Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy. PLOS ONE 2016, 11: e0164319. PMID: 27716814, PMCID: PMC5055363, DOI: 10.1371/journal.pone.0164319.Peer-Reviewed Original ResearchConceptsPaclitaxel-induced neuropathySevere neuropathyReceiver operating characteristicNerve tissueDose-limiting toxicityEarly breast cancerSensory peripheral neuropathyArea under the curveBreast cancer patientsIntensity of stainingWeekly paclitaxelSurgical resectionCharcot-Marie-ToothLimiting toxicitiesPredictive biomarkersNerve biopsyPeripheral neuropathyBreast cancerBiomarker strategiesCancer patientsNDRG1 expressionNeuropathyExpression scorePatientsPaclitaxel
2015
Hypothermia for preventing chemotherapy-induced neuropathy – a pilot study on safety and tolerability in healthy controls
Bandla A, Sundar R, Liao L, Tan S, Lee S, Thakor N, Wilder-Smith E. Hypothermia for preventing chemotherapy-induced neuropathy – a pilot study on safety and tolerability in healthy controls. Acta Oncologica 2015, 55: 430-436. PMID: 26360921, DOI: 10.3109/0284186x.2015.1075664.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyHealthy human subjectsHealthy subjectsSevere chemotherapy-induced peripheral neuropathyDose-limiting side effectReduced nerve blood flowSeverity of chemotherapy-induced peripheral neuropathyLimb hypothermiaAdjuvant weekly paclitaxelChemotherapy-induced neuropathyNerve blood flowDuration of chemotherapyBreast cancer patientsSuccess of chemotherapyInfluence of hypothermiaEffects of hypothermiaWeekly paclitaxelSignificant adverse effectsPaclitaxel chemotherapyTreatment discontinuationTransient numbnessDose-relatedNeurotoxic drugsHuman subjectsCancer subjects
2014
Phase II study of neoadjuvant weekly paclitaxel and carboplatin with lapatinib in HER2+ breast cancer.
Wong A, Tan S, Soh I, Tan C, Lim Y, Pang A, Ho J, Ow S, Sundar R, Pang M, Chan C, Buhari S, Hartman M, Iau P, Tang A, Wong N, Yap Y, Khoo B, Thiery J, Lee S. Phase II study of neoadjuvant weekly paclitaxel and carboplatin with lapatinib in HER2+ breast cancer. Journal Of Clinical Oncology 2014, 32: 619-619. DOI: 10.1200/jco.2014.32.15_suppl.619.Peer-Reviewed Original Research