title: Dose escalation to rash for erlotinib plus gemcitabine for metastatic pancreatic cancer: the phase II RACHEL study.
abstract: BACKGROUND
  This phase II, open-label, randomised study evaluated whether patients with metastatic pancreatic cancer receiving erlotinib/gemcitabine derived survival benefits from increasing the erlotinib dose.
  
  
  METHODS
  After a 4-week run-in period (gemcitabine 1000 mg m(-2) once weekly plus erlotinib 100 mg per day), patients with metastatic pancreatic cancer who developed grade 0/1 rash were randomised to receive gemcitabine plus erlotinib dose escalation (150 mg, increasing by 50 mg every 2 weeks (maximum 250 mg); n=71) or gemcitabine plus standard-dose erlotinib (100 mg per day; n=75). The primary end point was to determine whether overall survival (OS) was improved by increasing the erlotinib dose. Secondary end points included progression-free survival (PFS), incidence of grade ⩾2 rash, and safety.
  
  
  RESULTS
  Erlotinib dose escalation induced grade ⩾2 rash in 29 out of 71 (41.4%) patients compared with 7 out of 75 (9.3%) patients on standard dose. Efficacy was not significantly different in the dose-escalation arm compared with the standard-dose arm (OS: median 7.0 vs 8.4 months, respectively, hazard ratio (HR), 1.26, 95% confidence interval (CI): 0.88-1.80; P=0.2026; PFS: median 3.5 vs 4.5 months, respectively, HR, 1.09, 95% CI: 0.77-1.54; P=0.6298). Incidence of adverse events was comparable between randomised arms.
  
  
  CONCLUSIONS
  The erlotinib dose-escalation strategy induced rash in some patients; there was no evidence that the higher dose translated into increased benefit.
authors.affiliation: Gastroenterology/Digestive Oncology, University Hospitals Leuven and KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: 1] Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City, Taiwan [2] National Yang-Ming University School of Medicine, No. 155, Sec. 2, Linong Street, Taipei 112, Taiwan.
authors.forename: C-P
authors.initials: CP
authors.lastname: Li
authors.affiliation: Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Oddział w Gliwicach, ul. Wybrzeże Armii Krajowej 15, 44-101 Gliwice, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Nowara
authors.affiliation: Department of Medical Oncology, University Hospital of Udine, 33100 Udine, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Aprile
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Moore
authors.affiliation: NZOZ Magodent, Fieldorfa 40, 04-0125 Warsaw, Poland.
authors.forename: I
authors.initials: I
authors.lastname: Federowicz
authors.affiliation: Department of Gastroenterology-GI Cancer Unit, Erasme University Hospital-ULB-Brussels, Route de Lennik 808, 1070 Brussels, Belgium.
authors.forename: J-L
authors.initials: JL
authors.lastname: Van Laethem
authors.affiliation: National Taiwan University Hospital, No.1 Changde Street, Zhongzheng District, Taipei City 10048, Taiwan.
authors.forename: C
authors.initials: C
authors.lastname: Hsu
authors.affiliation: Department of Medical Oncology, National Cancer Center Singapore, 11 Hospital Drive, Singapore 169610, Singapore.
authors.forename: C K
authors.initials: CK
authors.lastname: Tham
authors.affiliation: Institute of Oncology, Davidoff Center, Rabin Medical Center, 39 Jabotinski Street, Petah Tikva 49100, Israel.
authors.forename: S M
authors.initials: SM
authors.lastname: Stemmer
authors.affiliation: GermanOncology GmbH, Überseeallee 1, D-20457 Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Lipp
authors.affiliation: Roche Products Ltd, 6 Falcon Way, Shire Park, Hexagon Place Welwyn Garden City, Hertfordshire AL7 1TW, UK.
authors.forename: A
authors.initials: A
authors.lastname: Zeaiter
authors.affiliation: Roche Products Ltd, 6 Falcon Way, Shire Park, Hexagon Place Welwyn Garden City, Hertfordshire AL7 1TW, UK.
authors.forename: A
authors.initials: A
authors.lastname: Fittipaldo
authors.affiliation: F. Hoffmann-La Roche, CH-4070 Basel, Switzerland.
authors.forename: Z
authors.initials: Z
authors.lastname: Csutor
authors.affiliation: F. Hoffmann-La Roche, CH-4070 Basel, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Klughammer
authors.affiliation: PD Biostatistics, Roche, 720 Cai Lun Road, Building 5, Shanghai 201203, Pudong, China.
authors.forename: X
authors.initials: X
authors.lastname: Meng
authors.affiliation: Institute of Oncology Ion Chiricuta and UMF Iuliu Hatieganu, Cluj-Napoca 400015, Romania.
authors.forename: T
authors.initials: T
authors.lastname: Ciuleanu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000093542:Gemcitabine