6533b7defe1ef96bd1276964
RESEARCH PRODUCT
Phase I study of FOLFIRI plus pimasertib as second-line treatment for KRAS-mutated metastatic colorectal cancer
Teresa Macarulla MercadéAndrés CervantesJosep TaberneroSusana RosellóE. Van CutsemS. TejparH. PrenenE. MartinelliT. TroianiB. LaffranchiV JegoO. Von RichterFortunato CiardielloUniversitat Autònoma De Barcelonasubject
MaleCancer ResearchColorectal cancermedicine.medical_treatmentLeucovorinColorectal NeoplasmPharmacologymedicine.disease_causepimasertibcombination therapyAntineoplastic Combined Chemotherapy ProtocolsNeoplasm Metastasiscombination therapy second-line treatmentAged 80 and overProto-Oncogene ProteinCetuximabKRAS-mutated metastatic colorectal cancerMedicine (all)MEK inhibitorMiddle AgedNeoplasm MetastasiTreatment OutcomeOncologyFluorouracilFOLFIRISecond-line treatmentFemaleFluorouracilKRASColorectal NeoplasmsPimasertibHumanmedicine.drugNiacinamideProto-Oncogene Proteins p21(ras)FOLFIRIProto-Oncogene ProteinsmedicineHumansCombination therapyneoplasmsAgedChemotherapyMEK inhibitorAntineoplastic Combined Chemotherapy Protocolbusiness.industryKRAS -mutated metastatic colorectal cancerGenes raras Proteinmedicine.diseasedigestive system diseasesGenes rassecond-line treatmentMutationras ProteinsClinical StudyCancer researchCamptothecinHuman medicinebusinessCamptothecindescription
BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway has been implicated in the molecular pathogenesis of human cancers, including metastatic colorectal cancer (mCRC). This provides a rationale for the development of MAPK-targeted agents such as pimasertib. METHODS: Patients with KRAS mutant mCRC were treated in the second-line setting with FOLFIRI (5-fluorouracil/folinic acid/irinotecan) plus pimasertib. The primary objective of the safety run-in phase was to determine the maximum-tolerated dose (MTD) and the recommended phase II dose of pimasertib combined with FOLFIRI. RESULTS: Sixteen patients were enrolled in the trial. Ten and six patients were treated daily with 45 and 60 mg of pimasertib plus FOLFIRI, respectively. The MTD was considered to be 45 mg per day. The most common treatment-emergent adverse events were diarrhoea, nausea, vomiting, asthenia and skin/rash event. Of the 15 patients in the efficacy analysis group, two patients had partial response, nine patients had stable disease, three patients had progressive disease as their best overall response and one patient could not be evaluated. CONCLUSIONS: Dose escalation of pimasertib in combination with FOLFIRI was limited by toxicity. At the MTD of 45 mg per day, pimasertib was adequately tolerated in patients with mCRC and no unexpected or new safety signals or concerns were identified. ispartof: British Journal of Cancer vol:112 issue:12 pages:1874-1881 ispartof: location:England status: published
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 | The British journal of cancer |