PMID- 31367538
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220409
IS  - 2218-6751 (Print)
IS  - 2226-4477 (Electronic)
IS  - 2218-6751 (Linking)
VI  - 8
IP  - 3
DP  - 2019 Jun
TI  - A phase I/II study of pemetrexed with sirolimus in advanced, previously treated 
      non-small cell lung cancer.
PG  - 247-257
LID - 10.21037/tlcr.2019.04.19 [doi]
AB  - BACKGROUND: Single-agent pemetrexed is a treatment for recurrent non-squamous 
      non-small cell lung cancer (NSCLC) that provides limited benefit. Preclinical 
      studies showed promising synergistic effects when the mammalian target of 
      rapamycin (mTOR) inhibitor sirolimus was added to pemetrexed. METHODS: This was a 
      single-institution phase I/II study of pemetrexed in combination with sirolimus. 
      The primary endpoint for the phase I was to determine the maximum tolerated dose 
      (MTD) and safety of the combination. The primary endpoint for the phase II 
      portion was to determine the overall response rate at the MTD. Key eligibility 
      criteria included recurrent, metastatic NSCLC, ECOG performance status of 0-2, 
      and adequate organ function. Sirolimus was administered orally daily after an 
      initial loading dose, and pemetrexed was given intravenously on day 1 of every 
      21-day cycle. RESULTS: Forty-two patients with recurrent, metastatic NSCLC were 
      enrolled, 22 in phase I and 20 in phase II. The MTD was pemetrexed 500 mg/m(2) 
      every 3 weeks, and sirolimus 10 mg on day 1, and 3 mg daily thereafter. 
      Treatment-related adverse events (AEs) occurred in 38 (90.5%) patients. The most 
      common grade 3-4 treatment-related AEs were lymphopenia (31%) and 
      hypophosphatemia (19%). Two treatment-related deaths occurred due to febrile 
      neutropenia and infection, respectively. Among 27 total patients treated at the 
      MTD, 6 (22.2%) had a partial response (PR), 12 (44.4%) had stable disease (SD) 
      and 5 (18.5%) had progressive disease. Median progression-free survival (PFS) was 
      18.4 weeks (95% CI: 7.0-29.4). CONCLUSIONS: The combination of pemetrexed and 
      sirolimus is active in heavily-pretreated NSCLC (ClinicalTrials.gov Identifier: 
      NCT00923273).
FAU - Komiya, Takefumi
AU  - Komiya T
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Memmott, Regan M
AU  - Memmott RM
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Blumenthal, Gideon M
AU  - Blumenthal GM
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Bernstein, Wendy
AU  - Bernstein W
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Ballas, Marc S
AU  - Ballas MS
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - De Chowdhury, Roopa
AU  - De Chowdhury R
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Chun, Guinevere
AU  - Chun G
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Peer, Cody J
AU  - Peer CJ
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Figg, William D
AU  - Figg WD
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Liewehr, David J
AU  - Liewehr DJ
AD  - Biostatistics and Data Management Section, National Cancer Institute, Rockville, 
      MD, USA.
FAU - Steinberg, Seth M
AU  - Steinberg SM
AD  - Biostatistics and Data Management Section, National Cancer Institute, Rockville, 
      MD, USA.
FAU - Giaccone, Giuseppe
AU  - Giaccone G
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Szabo, Eva
AU  - Szabo E
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
AD  - Lung and Upper Aerodigestive Cancer Research Group, Division of Cancer 
      Prevention, National Cancer Institute, Bethesda, MD, USA.
FAU - Kawabata, Shigeru
AU  - Kawabata S
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Tsurutani, Junji
AU  - Tsurutani J
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Rajan, Arun
AU  - Rajan A
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
FAU - Dennis, Phillip A
AU  - Dennis PA
AD  - Medical Oncology Service, Center for Cancer Research, National Cancer Institute, 
      Bethesda, MD, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00923273
PT  - Journal Article
PL  - China
TA  - Transl Lung Cancer Res
JT  - Translational lung cancer research
JID - 101646875
PMC - PMC6626857
OTO - NOTNLM
OT  - Lung cancer
OT  - pemetrexed
OT  - phase I/II, sirolimus
OT  - thymidylate synthase (TS)
COIS- Conflicts of Interest: Phillip A. Dennis is employed by Astrazeneca and owns its 
      stocks. Marc S. Ballas is employed by GlaxoSmithKline and receives personal fees 
      from Astrazeneca and Bristol Myers Squibb. The other authors have no conflicts of 
      interest to declare.
EDAT- 2019/08/02 06:00
MHDA- 2019/08/02 06:01
PMCR- 2019/06/01
CRDT- 2019/08/02 06:00
PHST- 2019/08/02 06:00 [entrez]
PHST- 2019/08/02 06:00 [pubmed]
PHST- 2019/08/02 06:01 [medline]
PHST- 2019/06/01 00:00 [pmc-release]
AID - tlcr-08-03-247 [pii]
AID - 10.21037/tlcr.2019.04.19 [doi]
PST - ppublish
SO  - Transl Lung Cancer Res. 2019 Jun;8(3):247-257. doi: 10.21037/tlcr.2019.04.19.