PMID- 21989766
OWN - NLM
STAT- MEDLINE
DCOM- 20120420
LR  - 20211020
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Print)
IS  - 0344-5704 (Linking)
VI  - 69
IP  - 3
DP  - 2012 Mar
TI  - A phase I dose-escalation and pharmacokinetic study of sunitinib in combination 
      with pemetrexed in patients with advanced solid malignancies, with an expanded 
      cohort in non-small cell lung cancer.
PG  - 709-22
LID - 10.1007/s00280-011-1755-0 [doi]
AB  - PURPOSE: The primary objective of this phase I dose-escalation study was to 
      identify the maximum tolerated dose (MTD) of sunitinib plus pemetrexed in 
      patients with advanced cancer. METHODS: Using a 3 + 3 dose-escalation design, 
      patients received oral sunitinib qd by continuous daily dosing (CDD schedule; 
      37.5 or 50 mg) or 2 weeks on/1 week off treatment schedule (Schedule 2/1; 50 mg). 
      Pemetrexed (300-500 mg/m(2) IV) was administered q3w. At the proposed recommended 
      phase 2 dose (RP2D), additional patients with non-small cell lung cancer (NSCLC) 
      were enrolled. RESULTS: Thirty-five patients were enrolled on the CDD schedule 
      and seven on Schedule 2/1. MTDs were sunitinib 37.5 mg/day (CDD/RP2D) or 50 
      mg/day (Schedule 2/1) with pemetrexed 500 mg/m(2). Dose-limiting toxicities 
      included grade (G) 5 cerebral hemorrhage, G3 febrile neutropenia, and G3 
      anorexia. Common G3/4 drug-related non-hematologic adverse events (AEs) at the 
      CDD MTD included fatigue, anorexia, and hand-foot syndrome. G3/4 hematologic AEs 
      included lymphopenia, neutropenia, and thrombocytopenia. No significant drug-drug 
      interactions were identified. Five (24%) NSCLC patients had partial responses. 
      CONCLUSIONS: In patients with advanced solid malignancies, the MTD of sunitinib 
      plus 500 mg/m(2) pemetrexed was 37.5 mg/day (CDD schedule) or 50 mg/day (Schedule 
      2/1). The CDD schedule MTD was tolerable and demonstrated promising clinical 
      benefit in NSCLC.
FAU - Chow, L Q M
AU  - Chow LQ
AD  - The Ottawa Hospital Cancer Centre, Ottawa, Canada. lchow@seattlecca.org
FAU - Blais, N
AU  - Blais N
FAU - Jonker, D J
AU  - Jonker DJ
FAU - Laurie, S A
AU  - Laurie SA
FAU - Diab, S G
AU  - Diab SG
FAU - Canil, C
AU  - Canil C
FAU - McWilliam, M
AU  - McWilliam M
FAU - Thall, A
AU  - Thall A
FAU - Ruiz-Garcia, A
AU  - Ruiz-Garcia A
FAU - Zhang, K
AU  - Zhang K
FAU - Tye, L
AU  - Tye L
FAU - Chao, R C
AU  - Chao RC
FAU - Camidge, D R
AU  - Camidge DR
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20111012
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Glutamates)
RN  - 0 (Indoles)
RN  - 0 (Pyrroles)
RN  - 04Q9AIZ7NO (Pemetrexed)
RN  - 5Z93L87A1R (Guanine)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse 
      effects/*pharmacokinetics/therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/metabolism
MH  - Cohort Studies
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Glutamates/administration & dosage/adverse effects/pharmacokinetics/therapeutic 
      use
MH  - Guanine/administration & dosage/adverse effects/analogs & 
      derivatives/pharmacokinetics/therapeutic use
MH  - Humans
MH  - Indoles/administration & dosage/adverse effects/pharmacokinetics/therapeutic use
MH  - Lung Neoplasms/*drug therapy/metabolism
MH  - Male
MH  - Maximum Tolerated Dose
MH  - Middle Aged
MH  - Pemetrexed
MH  - Pyrroles/administration & dosage/adverse effects/pharmacokinetics/therapeutic use
MH  - Sunitinib
MH  - Treatment Outcome
PMC - PMC3286593
EDAT- 2011/10/13 06:00
MHDA- 2012/04/21 06:00
PMCR- 2011/10/12
CRDT- 2011/10/13 06:00
PHST- 2011/04/28 00:00 [received]
PHST- 2011/09/12 00:00 [accepted]
PHST- 2011/10/13 06:00 [entrez]
PHST- 2011/10/13 06:00 [pubmed]
PHST- 2012/04/21 06:00 [medline]
PHST- 2011/10/12 00:00 [pmc-release]
AID - 1755 [pii]
AID - 10.1007/s00280-011-1755-0 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2012 Mar;69(3):709-22. doi: 
      10.1007/s00280-011-1755-0. Epub 2011 Oct 12.