Featured Publications
Machine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial
Sundar R, Kumarakulasinghe N, Chan Y, Yoshida K, Yoshikawa T, Miyagi Y, Rino Y, Masuda M, Guan J, Sakamoto J, Tanaka S, Tan A, Hoppe M, Jeyasekharan A, Ng C, De Simone M, Grabsch H, Lee J, Oshima T, Tsuburaya A, Tan P. Machine-learning model derived gene signature predictive of paclitaxel survival benefit in gastric cancer: results from the randomised phase III SAMIT trial. Gut 2021, 71: 676-685. PMID: 33980610, PMCID: PMC8921574, DOI: 10.1136/gutjnl-2021-324060.Peer-Reviewed Original ResearchConceptsDisease free survivalValidation cohortGastric cancerGene signatureSurvival benefitPac-SensitiveNo survival differenceSelection of patientsGC trialsFree survivalPaclitaxel chemotherapyCurative surgeryMetastatic patientsPredictive biomarkersTraining cohortSurvival differencesIndependent cohortNanoString panelGC patientsPaclitaxelPatientsNanoString profilingCohortGroup trialUFT
2023
Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS)
Shitara K, George B, Taieb J, Sundar R, Fakih M, Makris L, Benhadji K, Ghidini M. Effects of prior therapies on outcomes with trifluridine/tipiracil in patients with metastatic gastric/gastroesophageal junction cancer in a randomized phase III trial (TAGS). Journal Of Cancer Research And Clinical Oncology 2023, 149: 9361-9374. PMID: 37213030, PMCID: PMC10374776, DOI: 10.1007/s00432-023-04813-z.Peer-Reviewed Original ResearchConceptsProgression-free survivalGastric/gastroesophageal junction cancerJunction cancerSurvival benefitSafety profileEastern Cooperative Oncology Group performance statusRandomized phase III trialAssociated with survival benefitMedian overall survivalPhase III trialsPost hoc exploratory analysisLater-lineTrifluridine/tipiracil treatmentHematologic toxicityPrior therapyMedian overallOverall survivalIII trialsPlacebo armPerformance statusResultsBaseline characteristicsMedian timeRamucirumabTherapy patternsClinical trials
2022
Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases
Chia D, Sundar R, Kim G, Ang J, Lum J, Nga M, Goh G, Seet J, Chee C, Tan H, Ho J, Ngoi N, Lee M, Muthu V, Chan G, Pang A, Ang Y, Choo J, Lim J, Teh J, Lwin A, Soon Y, Shabbir A, So J, Yong W. Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases. Annals Of Surgical Oncology 2022, 29: 8597-8605. PMID: 36070113, DOI: 10.1245/s10434-022-11998-z.Peer-Reviewed Original ResearchConceptsGastric cancer peritoneal metastasisIP-PTXConversion surgeryIntraperitoneal paclitaxelMedian OSSystemic chemotherapyPeritoneal metastasisSC groupConversion to negative cytologyResultsThe median OSProgression-free survivalPhase II studyMethodsForty-four patientsIntravenous oxaliplatinMedian PFSOral capecitabineSystemic capecitabineExtraperitoneal metastasesNegative cytologyPeritoneal diseaseOverall survivalPerformance statusPrimary endpointSecondary endpointsIP cohortPhase 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
2020
Safety, pharmacokinetics and tissue penetration of PIPAC paclitaxel in a swine model
Tan H, Kim G, Charles C, Li R, Jang C, Shabbir A, Chue K, Tai C, Sundar R, Goh B, Bonney G, Looi W, Cheow E, So J, Wang L, Yong W. Safety, pharmacokinetics and tissue penetration of PIPAC paclitaxel in a swine model. European Journal Of Surgical Oncology 2020, 47: 1124-1131. PMID: 32800400, DOI: 10.1016/j.ejso.2020.06.031.Peer-Reviewed Original ResearchConceptsSolvent-based paclitaxelAdverse eventsGrade 2 hypersensitivity reactionSystemic exposure to paclitaxelAbsolute neutrophil countExposure to paclitaxelPhase I studyShort-term safetySignificant adverse eventsTissue drug concentrationsConcentrations of paclitaxelPotential adverse eventsYorkshire x Landrace pigsPeritoneal carcinomatosisPeritoneal biopsiesNeutrophil countPeritoneal surfaceToxicity profileBlood countIV infusionPeritoneal cavityPharmacokinetic analysisClinical trialsHigh dosesPharmacokinetic comparison
2019
Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy
Bandla A, Tan S, Kumarakulasinghe N, Huang Y, Ang S, Magarajah G, Hairom Z, Lim J, Wong A, Chan G, Ngoi N, Ang E, Lee Y, Chan A, Lee S, Thakor N, Wilder-Smith E, Sundar R. Safety and tolerability of cryocompression as a method of enhanced limb hypothermia to reduce taxane-induced peripheral neuropathy. Supportive Care In Cancer 2019, 28: 3691-3699. PMID: 31811482, PMCID: PMC7316694, DOI: 10.1007/s00520-019-05177-2.Peer-Reviewed Original ResearchConceptsNerve conduction studiesTotal Neuropathy ScoreFrozen glovesTaxane chemotherapyNeuropathy scorePeripheral neuropathyDose-limiting toxicityConcomitant with chemotherapyTaxane-induced peripheral neuropathySeverity of neuropathySensory nerve amplitudesPrevention of neurotoxicitySkin temperature reductionLimb hypothermiaMonths post-chemotherapyPaclitaxel chemotherapyNerve amplitudeMotor amplitudeSevere neuropathyPost-chemotherapyUndesired side effectsChemotherapyCancer patientsNeuropathySide effects
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
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