2019
Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer.
Argiris A, Li S, Savvides P, Ohr JP, Gilbert J, Levine MA, Chakravarti A, Haigentz M, Saba NF, Ikpeazu CV, Schneider CJ, Pinto HA, Forastiere AA, Burtness B. Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer. Journal Of Clinical Oncology 2019, 37: 3266-3274. PMID: 31618129, PMCID: PMC6980834, DOI: 10.1200/jco.19.00555.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBevacizumabDisease ProgressionDrug Administration ScheduleFemaleHead and Neck NeoplasmsHumansMaleNeoplasm Recurrence, LocalProgression-Free SurvivalSquamous Cell Carcinoma of Head and NeckTime FactorsUnited StatesConceptsAddition of bevacizumabProgression-free survivalOverall survivalResponse rateMedian progression-free survivalMetastatic squamous cell carcinomaPlatinum-based chemotherapy doubletsTreatment-related grade 3Phase III randomized trialsTreatment-related deathsMedian overall survivalPlatinum-based chemotherapySquamous cell carcinomaBetter toxicity profileBiomarker-driven studiesOverall response rateHumanized monoclonal antibodyVascular endothelial growth factorEndothelial growth factorChemotherapy doubletsMedian OSMetastatic SCCHNOS ratesEligible patientsMetastatic head
2018
Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study
Cohen EEW, Soulières D, Le Tourneau C, Dinis J, Licitra L, Ahn MJ, Soria A, Machiels JP, Mach N, Mehra R, Burtness B, Zhang P, Cheng J, Swaby RF, Harrington KJ, investigators K, Acosta-Rivera M, Adkins D, Aghmesheh M, Ahn M, Airoldi M, Aleknavicius E, Al-Farhat Y, Algazi A, Almokadem S, Alyasova A, Bauman J, Benasso M, Berrocal A, Bray V, Burtness B, Caponigro F, Castro A, Cescon T, Chan K, Chaudhry A, Chauffert B, Cohen E, Csoszi T, De Boer J, Delord J, Dietz A, Dinis J, Dupuis C, Digue L, Erfan J, Alvarez Y, Evans M, Fidler M, Forster M, Friesland S, Ganti A, Geoffrois L, Grant C, Gruenwald V, Harrington K, Hoffmann T, Horvai G, Inciura A, Jang R, Jankowska P, Jimeno A, Joseph M, Ramiro A, Karaszewska B, Kawecki A, Keilholz U, Keller U, Kim S, Kocsis J, Kotecki N, Kozloff M, Lambea J, Landherr L, Lantsukhay Y, Lazarev S, Lee L, Le Tourneau C, Licitra L, Lifirenko I, Mach N, Martincic D, Matorin O, McGrath M, Machiels J, Mehra R, Misiukiewicz K, Morris J, Mufazalov F, Niu J, Srinivasan D, Segura P, Rauch D, Ribeiro M, Rodriguez C, Rolland F, Russo A, Ruzsa A, Sanches F, Shin S, Shtiveland M, Soulieres D, Soria A, Specenier P, Szekanecz E, Szota J, van Herpen C, Velez-Cortes H, Walsh W, Wilop S, Winterhalder R, Wojtukiewicz M, Wong D, Zandberg D. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. The Lancet 2018, 393: 156-167. PMID: 30509740, DOI: 10.1016/s0140-6736(18)31999-8.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCetuximabDisease ProgressionDocetaxelDrug Administration ScheduleFemaleHead and Neck NeoplasmsHumansKaplan-Meier EstimateMaleMethotrexateMiddle AgedNeoplasm Recurrence, LocalSquamous Cell Carcinoma of Head and NeckConceptsNeck squamous cell carcinomaSquamous cell carcinomaStandard of careTreatment-related adverse eventsCell carcinomaMetastatic headOverall survivalTreat populationAdverse eventsCommon treatment-related adverse eventsWorse treatment-related adverse eventsPlatinum-containing treatmentTreatment-related deathsMedian overall survivalWeb response systemEffective treatment optionFavorable safety profileEarly phase trialsTreatment of headSubsidiary of MerckManageable toxicityMeaningful prolongationAdvanced diseasePrimary endpointMetastatic diseaseRadiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial
Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B, Ridge JA, Ringash J, Galvin J, Yao M, Koyfman SA, Blakaj DM, Razaq MA, Colevas AD, Beitler JJ, Jones CU, Dunlap NE, Seaward SA, Spencer S, Galloway TJ, Phan J, Dignam JJ, Le QT. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. The Lancet 2018, 393: 40-50. PMID: 30449625, PMCID: PMC6541928, DOI: 10.1016/s0140-6736(18)32779-x.Peer-Reviewed Original ResearchConceptsHPV-positive oropharyngeal carcinomaProgression-free survivalOverall survivalNon-inferiority trialCisplatin groupCetuximab groupOropharyngeal carcinomaSevere toxicityEligibility criteriaPositive oropharyngeal squamous cell carcinomaHuman papillomavirus-positive oropharyngeal cancerNational Cancer Institute-USAZubrod performance status 0Oropharyngeal squamous cell carcinomaAdequate bone marrowPerformance status 0Replacement of cisplatinZubrod performance statusInferior overall survivalTobacco smoking historyAmerican Joint CommitteeNon-inferiority criteriaSquamous cell carcinomaStandard of careNon-inferiority margin
2016
E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx— ECOG-ACRIN Cancer Research Group
Marur S, Li S, Cmelak AJ, Gillison ML, Zhao WJ, Ferris RL, Westra WH, Gilbert J, Bauman JE, Wagner LI, Trevarthen DR, Balkrishna J, Murphy BA, Agrawal N, Colevas AD, Chung CH, Burtness B. E1308: Phase II Trial of Induction Chemotherapy Followed by Reduced-Dose Radiation and Weekly Cetuximab in Patients With HPV-Associated Resectable Squamous Cell Carcinoma of the Oropharynx— ECOG-ACRIN Cancer Research Group. Journal Of Clinical Oncology 2016, 35: 490-497. PMID: 28029303, PMCID: PMC5455313, DOI: 10.1200/jco.2016.68.3300.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCetuximabChemoradiotherapyDisease-Free SurvivalDrug Administration ScheduleExanthemaFemaleHuman papillomavirus 16HumansInduction ChemotherapyMaleMiddle AgedNeutropeniaOropharyngeal NeoplasmsPapillomavirus InfectionsRadiotherapy DosageRemission InductionConceptsOropharyngeal squamous cell carcinomaComplete clinical responseCycle of ICPhase II trialProgression-free survivalSquamous cell carcinomaWeekly cetuximabII trialCell carcinomaPack-year smoking historyResectable squamous cell carcinomaFavorable-risk patientsPrimary end pointOverall survival rateHigh cure ratesCancer Research GroupGy of radiationRadiation doseLong-term toxicityRadiation dose reductionChemoradiation resultsICS respondersInduction chemotherapyLate sequelaeClinical response
2013
Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial
Argiris A, Ghebremichael M, Gilbert J, Lee JW, Sachidanandam K, Kolesar JM, Burtness B, Forastiere AA. Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial. Journal Of Clinical Oncology 2013, 31: 1405-1414. PMID: 23460714, PMCID: PMC3612594, DOI: 10.1200/jco.2012.45.4272.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellDiarrheaDocetaxelDrug Administration ScheduleErbB ReceptorsFatigueFemaleGefitinibGenotypeHead and Neck NeoplasmsHumansKaplan-Meier EstimateLeukopeniaMaleMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalProto-Oncogene ProteinsProto-Oncogene Proteins c-metProto-Oncogene Proteins p21(ras)QuinazolinesRas ProteinsTaxoidsTreatment OutcomeConceptsAddition of gefitinibPerformance statusArm ADisease progressionEastern Cooperative Oncology Group performance statusEastern Cooperative Oncology Group trialEpidermal growth factor receptor tyrosine kinase inhibitorsGrowth factor receptor tyrosine kinase inhibitorsReceptor tyrosine kinase inhibitorsGrade 3/4 diarrheaPhase III randomizedSingle-agent gefitinibTrials of docetaxelUnplanned subset analysisECOG performance statusGrade 3/4 toxicitiesMedian overall survivalTime of progressionSquamous cell carcinomaTyrosine kinase inhibitorsEligible patientsMetastatic SCCHNWeekly docetaxelMetastatic headOverall survival
2010
Initial Results of a Phase I Dose-Escalation Trial of Concurrent and Maintenance Erlotinib and Reirradiation for Recurrent and New Primary Head-and-Neck Cancer
Rusthoven KE, Feigenberg SJ, Raben D, Kane M, Song JI, Nicolaou N, Mehra R, Burtness B, Ridge J, Swing R, Lango M, Cohen R, Jimeno A, Chen C. Initial Results of a Phase I Dose-Escalation Trial of Concurrent and Maintenance Erlotinib and Reirradiation for Recurrent and New Primary Head-and-Neck Cancer. International Journal Of Radiation Oncology • Biology • Physics 2010, 78: 1020-1025. PMID: 20231078, DOI: 10.1016/j.ijrobp.2009.09.003.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsCarcinoma, Squamous CellCetuximabCombined Modality TherapyDrug Administration ScheduleErlotinib HydrochlorideFeasibility StudiesFemaleFollow-Up StudiesGastrostomyHead and Neck NeoplasmsHumansMaleMiddle AgedNeoplasm Recurrence, LocalProtein Kinase InhibitorsQuinazolinesRadiotherapy DosageRetreatmentTreatment OutcomeConceptsDose-limiting toxicityMaintenance erlotinibPrimary HNCCohort IIICohort IINeck cancerCohort IPrimary headRadiation therapyPhase I dose-escalation trialPercutaneous endoscopic gastrostomy (PEG) tube placementAcute grade 3 toxicityGrade 4 acute toxicityI dose-escalation trialEndoscopic gastrostomy tube placementGrade 3 dysphagiaGrade 3 osteoradionecrosisNew primary headGrade 3 toxicityDose-escalation trialPhase I trialGastrostomy tube placementErlotinib dailyMaintenance therapyPrior radiation
2009
Phase II trial of docetaxel–irinotecan combination in advanced esophageal cancer
Burtness B, Gibson M, Egleston B, Mehra R, Thomas L, Sipples R, Quintanilla M, Lacy J, Watkins S, Murren JR, Forastiere AA. Phase II trial of docetaxel–irinotecan combination in advanced esophageal cancer. Annals Of Oncology 2009, 20: 1242-1248. PMID: 19429872, PMCID: PMC2699385, DOI: 10.1093/annonc/mdn787.Peer-Reviewed Original ResearchConceptsAdvanced esophageal cancerPartial responseComplete responseEligible patientsEsophageal cancerEastern Cooperative Oncology Group performance statusMetastatic squamous cell carcinomaSafety of docetaxelPhase II trialSquamous cell carcinomaPrincipal toxic effectsAssessable patientsEsophagogastric cancerMeasurable diseaseToxic deathsII trialCN patientsMedian survivalPerformance statusNormal bilirubinPreclinical evidenceMedian timeCell carcinomaMyocardial infarctionTumor assessment
2008
A randomized phase II study of ixabepilone (BMS-247550) given daily × 5 days every 3 weeks or weekly in patients with metastatic or recurrent squamous cell cancer of the head and neck: an Eastern Cooperative Oncology Group study
Burtness BA, Manola J, Axelrod R, Argiris A, Forastiere AA. A randomized phase II study of ixabepilone (BMS-247550) given daily × 5 days every 3 weeks or weekly in patients with metastatic or recurrent squamous cell cancer of the head and neck: an Eastern Cooperative Oncology Group study. Annals Of Oncology 2008, 19: 977-983. PMID: 18296423, DOI: 10.1093/annonc/mdm591.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibiotics, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Squamous CellCombined Modality TherapyDisease-Free SurvivalDocetaxelDrug Administration ScheduleDrug Resistance, NeoplasmEpothilonesFemaleHead and Neck NeoplasmsHematologic DiseasesHumansInfusions, IntravenousMaleMiddle AgedPaclitaxelPeripheral Nervous System DiseasesRecurrenceSalvage TherapySurvival AnalysisTaxoidsConceptsTaxane-naive patientsArm BEastern Cooperative Oncology Group performance statusEastern Cooperative Oncology Group StudyRecurrent squamous cell cancerSensory/motor neuropathyRandomized phase II studyMetastatic/recurrent diseaseCommon grade 3Grade 3 neuropathyPhase II studyPrimary end pointSquamous cell cancerSquamous cell carcinomaEligible patientsPrior regimensWeekly ixabepiloneRecurrent diseaseII studyMedian survivalPartial responsePerformance statusMotor neuropathyCell cancerCell carcinoma
2007
Phase II Trial of Weekly Docetaxel/Irinotecan Combination in Advanced Pancreatic Cancer
Burtness B, Thomas L, Sipples R, McGurk M, Salikooti S, Christoforou M, Mirto G, Salem R, Sosa J, Kloss R, Rahman Z, Chung G, Lacy J, Murren JR. Phase II Trial of Weekly Docetaxel/Irinotecan Combination in Advanced Pancreatic Cancer. The Cancer Journal 2007, 13: 257-262. PMID: 17762761, DOI: 10.1097/ppo.0b013e31813c1174.Peer-Reviewed Original ResearchConceptsAdvanced pancreatic cancerPancreatic cancerEligible patientsIrinotecan combinationPartial responseComplete responseEastern Cooperative Oncology Group performance status 0Principal grade 3/4 toxicitiesWorld Health Organization criteriaSafety of docetaxelGrade 3/4 toxicitiesObjective response ratePerformance status 0One-year survivalPhase II trialCombination of docetaxelNormal bilirubin levelsEvaluable patientsFebrile neutropeniaMeasurable diseaseStatus 0Toxic deathsUnresectable diseaseII trialRecurrent disease
2006
Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer
Abu-Khalaf MM, Juneja V, Chung GG, DiGiovanna MP, Sipples R, McGurk M, Zelterman D, Haffty B, Reiss M, Wackers FJ, Lee FA, Burtness BA. Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer. Breast Cancer Research And Treatment 2006, 104: 341-349. PMID: 17051423, DOI: 10.1007/s10549-006-9413-7.Peer-Reviewed Original ResearchConceptsLeft ventricular ejection fractionEnd of chemotherapyEquilibrium radionuclide angiographyBreast cancerAdjuvant therapySequential doxorubicinCardiac functionIpsilateral axillary lymph nodesHigh-risk breast cancerRisk breast cancerClinical heart failureInitiation of chemotherapyAxillary lymph nodesVentricular ejection fractionEnd of therapyLong-term cardiotoxicityMedian absolute changeEligible patientsFilgrastim supportLate cardiotoxicityAxillary nodesAsymptomatic declineEjection fractionHeart failureLymph nodesAntibody therapy for early-stage breast cancer: trastuzumab adjuvant and neoadjuvant trials
Mehra R, Burtness B. Antibody therapy for early-stage breast cancer: trastuzumab adjuvant and neoadjuvant trials. Expert Opinion On Biological Therapy 2006, 6: 951-962. PMID: 16918262, DOI: 10.1517/14712598.6.9.951.Peer-Reviewed Original ResearchConceptsBreast cancerVascular endothelial growth factor levelsEarly-stage breast cancerYear of trastuzumabHER2/neu geneGrowth factor levelsBreast cancer cellsAdjuvant settingNeoadjuvant trialsOverall survivalRandomised trialsAggressive courseImproved outcomesImmune responseTrastuzumabActivation initiatesFactor levelsHER2 phosphorylationMonoclonal antibodiesNeu geneCancerCancer cellsHER2TrialsAntibodies
2004
Cisplatin, Fluorouracil, and Leucovorin Induction Chemotherapy Followed by Concurrent Cisplatin Chemoradiotherapy for Organ Preservation and Cure in Patients With Advanced Head and Neck Cancer: Long-Term Follow-Up
Psyrri A, Kwong M, DiStasio S, Lekakis L, Kassar M, Sasaki C, Wilson LD, Haffty BG, Son YH, Ross DA, Weinberger PM, Chung GG, Zelterman D, Burtness BA, Cooper DL. Cisplatin, Fluorouracil, and Leucovorin Induction Chemotherapy Followed by Concurrent Cisplatin Chemoradiotherapy for Organ Preservation and Cure in Patients With Advanced Head and Neck Cancer: Long-Term Follow-Up. Journal Of Clinical Oncology 2004, 22: 3061-3069. PMID: 15284256, DOI: 10.1200/jco.2004.01.108.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBrachytherapyCarcinoma, Squamous CellCisplatinCombined Modality TherapyDrug Administration ScheduleFemaleFluorouracilFollow-Up StudiesHead and Neck NeoplasmsHumansLeucovorinMaleMiddle AgedQuality of LifeRemission InductionSurvival RateTreatment OutcomeConceptsConcurrent cisplatin chemoradiotherapyComplete response rateInduction chemotherapyCisplatin chemoradiotherapyOrgan preservationResponse rateAdvanced headGrade 3Survival rateProgression-free survival ratesNeck squamous cell carcinomaCommon grade 3Courses of cisplatinPartial response ratePhase II studyOverall survival ratePoor functional outcomeSquamous cell carcinomaExternal beam radiotherapyExcellent PFSResectable HNSCCAdvanced diseaseConcurrent chemoradiotherapyPersistent dysphagiaII study
2002
Phase I Dose Escalation Trial of Weekly Docetaxel Plus Irinotecan in Patients with Advanced Cancer
Bleickardt E, Argiris A, Rich R, Blum K, McKeon A, Tara H, Zelterman D, Burtness B, Davies MJ, Murren JR. Phase I Dose Escalation Trial of Weekly Docetaxel Plus Irinotecan in Patients with Advanced Cancer. Cancer Biology & Therapy 2002, 1: 646-651. PMID: 12642688, DOI: 10.4161/cbt.314.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityWeek of restWeekly docetaxelPancreatic cancerDose levelsSolid tumorsPredominant dose-limiting toxicityCommon dose-limiting toxicityNon-small cell lungPhase II dosesNausea/vomitingAdvanced solid tumorsMaximum-tolerated dosePhase II trialPhase I trialNonhematologic toxicityEligible patientsEscalation trialII trialPartial responseSevere neutropeniaWeekly administrationI trialAdvanced cancerCell lung
2000
Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer
Murren J, Peccerillo K, DiStasio S, Li X, Leffert J, Pizzorno G, Burtness B, McKeon A, Cheng Y. Dose escalation and pharmacokinetic study of irinotecan in combination with paclitaxel in patients with advanced cancer. Cancer Chemotherapy And Pharmacology 2000, 46: 43-50. PMID: 10912577, DOI: 10.1007/s002800000115.Peer-Reviewed Original ResearchConceptsDose of irinotecanElimination of irinotecanDrug AdministrationAdvanced cancerFirst cycle patientsChemotherapy-related toxicityDose of paclitaxelClinical side effectsSequence of administrationBlood cell elementsNonhematologic toxicityReversible neutropeniaFirst doseMost patientsPartial responseCycle patientsDose escalationMild diarrheaPreclinical dataPlasma concentrationsSide effectsIrinotecanPatientsPharmacokinetic parametersWeekly schedulePhase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin.
Baselga J, Pfister D, Cooper MR, Cohen R, Burtness B, Bos M, D’Andrea G, Seidman A, Norton L, Gunnett K, Falcey J, Anderson V, Waksal H, Mendelsohn J. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin. Journal Of Clinical Oncology 2000, 18: 904-14. PMID: 10673534, DOI: 10.1200/jco.2000.18.4.904.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsArea Under CurveCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellCetuximabCisplatinDose-Response Relationship, DrugDrug Administration ScheduleErbB ReceptorsFemaleGene Expression Regulation, NeoplasticHead and Neck NeoplasmsHumansInfusions, IntravenousLung NeoplasmsMaleNeoplasms, Glandular and EpithelialRecombinant Fusion ProteinsRemission InductionSafetyConceptsAntibody dosesMultiple doseSystemic clearancePhase I clinical trialWeeks of therapyDose-dependent pharmacokineticsCell lung cancerChimeric monoclonal antibodyCoadministration of cisplatinEpidermal growth factor receptorMurine chimeric monoclonal antibodyGrowth factor receptorDisease stabilizationPartial responseAdvanced tumorsSingle doseLung cancerClinical trialsDisease progressionEpithelial tumorsNonlinear pharmacokineticsPatientsDose levelsAntibody C225Relevant doses
1997
Dose-escalation and pharmacodynamic study of topotecan in combination with cyclophosphamide in patients with refractory cancer.
Murren JR, Anderson S, Fedele J, Pizzorno G, Belliveau D, Zelterman D, Burtness BA, Tocino I, Flynn SD, Beidler D, Cheng YC. Dose-escalation and pharmacodynamic study of topotecan in combination with cyclophosphamide in patients with refractory cancer. Journal Of Clinical Oncology 1997, 15: 148-57. PMID: 8996136, DOI: 10.1200/jco.1997.15.1.148.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsMaximum-tolerated doseMg/ m2/dDose of topotecanM2/dRefractory cancerDay 1Treatment cyclesDrug-induced DNA fragmentationGrowth factor supportTransfusion of RBCsDose of cyclophosphamideFirst treatment cycleAdministration of cyclophosphamideGranulocyte colony-stimulating factorPharmacokinetics of topotecanClass of agentsColony-stimulating factorBlood cell elementsBolus scheduleNonhematologic toxicityReversible neutropeniaDNA fragmentationFactor supportCombination therapy