PMID- 25837499
OWN - NLM
STAT- MEDLINE
DCOM- 20160405
LR  - 20221207
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 4
DP  - 2015
TI  - A phase I dose-escalation study of lenalidomide in combination with gemcitabine 
      in patients with advanced pancreatic cancer.
PG  - e0121197
LID - 10.1371/journal.pone.0121197 [doi]
LID - e0121197
AB  - PURPOSE: Lenalidomide have both immunomodulatory and anti-angiogenic properties 
      which could confer anti-cancer effects. The aim of this study was to assess the 
      feasibility of combining lenalidomide with the standard treatment gemcitabine in 
      pancreatic cancer patients with advanced disease. PATIENTS AND METHODS: Eligible 
      patients had locally advanced or metastatic adenocarcinoma of the pancreas. 
      Patients received lenalidomide days 1-21 orally and gemcitabine 1000 mg/m2 
      intravenously (days 1, 8 and 15), each 28 day cycle. Three cohorts of 
      lenalidomide were examined (Cohort I = 15 mg, Cohort II = 20 mg and Cohort III = 
      25 mg daily). The maximum tolerated dose (MTD) of lenalidomide given in 
      combination with gemcitabine was defined as the highest dose level at which no 
      more than one out of four (25%) subjects experiences a dose-limiting toxicity 
      (DLT). Patients should also be able to receive daily low molecular weight heparin 
      (LMWH) (e.g. dalteparin 5000 IU s.c. daily) as a prophylactic anticoagulant for 
      venous thromboembolic events (VTEs). Twelve patients (n = 4, n = 3 and n = 5 in 
      cohort I, II and III, respectively) were enrolled in this study. RESULTS: Median 
      duration of treatment was 11 weeks (range 1-66), and median number of treatment 
      cycles were three (range 1-14). The only DLT was a cardiac failure grade 3 in 
      cohort III. Frequent treatment-related adverse events (AEs) (all grades) included 
      neutropenia, leucopenia and fatigue (83% each, but there was no febrile 
      neutropenia); thrombocytopenia (75%); dermatological toxicity (75%); diarrhea and 
      nausea (42% each); and neuropathy (42%). DISCUSSION: This phase I study 
      demonstrates the feasibility of the combination of lenalidomide and gemcitabine 
      as first-line treatment in patients with advanced pancreatic cancer. The 
      tolerability profile demonstrated in the dose escalation schedule of lenalidomide 
      suggests the dosing of lenalidomide to be 25 mg daily on days 1-21 with standard 
      dosing of gemcitabine and merits further evaluation in a phase II trial. TRIAL 
      REGISTRATION: ClinicalTrials.gov NCT01547260.
FAU - Ullenhag, Gustav J
AU  - Ullenhag GJ
AD  - Department of Radiology, Oncology and Radiation Science, Section of Oncology, 
      Uppsala University, Uppsala, Sweden; Department of Oncology, Uppsala University 
      Hospital, Entrance 78, 751 85 Uppsala, Sweden.
FAU - Rossmann, Eva
AU  - Rossmann E
AD  - Department of Oncology and Pathology (Radiumhemmet), Cancer Centre Karolinska, 
      Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
FAU - Liljefors, Maria
AU  - Liljefors M
AD  - Department of Oncology and Pathology (Radiumhemmet), Cancer Centre Karolinska, 
      Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
LA  - eng
SI  - ClinicalTrials.gov/NCT01547260
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150402
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anticoagulants)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - F0P408N6V4 (Lenalidomide)
RN  - S79O08V79F (Dalteparin)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/pathology
MH  - Administration, Oral
MH  - Aged
MH  - Anticoagulants/therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects
MH  - Dalteparin/therapeutic use
MH  - Deoxycytidine/administration & dosage/adverse effects/*analogs & derivatives
MH  - Drug Administration Schedule
MH  - Fatigue/chemically induced/physiopathology
MH  - Female
MH  - Humans
MH  - Injections, Intravenous
MH  - Lenalidomide
MH  - Leukopenia/chemically induced/physiopathology
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Neutropenia/chemically induced/physiopathology
MH  - Pancreas/drug effects/pathology
MH  - Pancreatic Neoplasms/*drug therapy/pathology
MH  - Thalidomide/administration & dosage/adverse effects/*analogs & derivatives
MH  - Gemcitabine
PMC - PMC4383423
COIS- Competing Interests: The authors have read the journal's policy and one author of 
      this manuscript has the following competing interest. Maria Liljefors has 
      declared one compensated advisory role with Celgene Corporation. This does not 
      alter the authors' adherence to PLOS ONE policies on sharing data and materials. 
      The other authors have declared that no competing interests exist.
EDAT- 2015/04/04 06:00
MHDA- 2016/04/06 06:00
PMCR- 2015/04/02
CRDT- 2015/04/04 06:00
PHST- 2014/07/30 00:00 [received]
PHST- 2015/01/19 00:00 [accepted]
PHST- 2015/04/04 06:00 [entrez]
PHST- 2015/04/04 06:00 [pubmed]
PHST- 2016/04/06 06:00 [medline]
PHST- 2015/04/02 00:00 [pmc-release]
AID - PONE-D-14-19777 [pii]
AID - 10.1371/journal.pone.0121197 [doi]
PST - epublish
SO  - PLoS One. 2015 Apr 2;10(4):e0121197. doi: 10.1371/journal.pone.0121197. 
      eCollection 2015.