PMID- 19843072
OWN - NLM
STAT- MEDLINE
DCOM- 20100330
LR  - 20201212
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 101
IP  - 1
DP  - 2010 Jan
TI  - Phase I study of TLR9 agonist PF-3512676 in combination with carboplatin and 
      paclitaxel in patients with advanced non-small-cell lung cancer.
PG  - 188-95
LID - 10.1111/j.1349-7006.2009.01361.x [doi]
AB  - This phase I, open-label study investigated the Toll-like receptor 9 agonist, 
      PF-3512676, in combination with carboplatin and paclitaxel in Japanese patients 
      with advanced, non-small-cell lung cancer (NSCLC). Patients (n = 12) with 
      treatment-naive stage IIIB or IV NSCLC received single-agent PF-3512676 
      subcutaneously once during the first 7 days (monotherapy phase) in three 
      escalating dose levels (0.1, 0.2, and 0.4 mg/kg) followed by a combination phase 
      during which patients received 0.1 or 0.2 mg/kg PF-3512676 subcutaneously on days 
      8 and 15 of each 3-week cycle of carboplatin (area under the curve, 6 mg x 
      min/mL) and paclitaxel (200 mg/m(2)). Safety and pharmacokinetics of PF-3512676 
      were assessed during monotherapy and combination therapy phases. PF-3512676 was 
      tolerable as monotherapy or in combination with chemotherapy in patients with 
      NSCLC. Most common treatment-related, non-hematologic adverse events (AEs) 
      throughout the study were injection-site reactions (n = 12, 100%) and flu-like 
      symptoms (n = 11, 91.7%) that were each grade 1 or 2 in all but one patient. All 
      patients experienced neutropenia and leukopenia (>or=grade 3 in 11 [91.7%] and 
      seven [58.3%] patients, respectively). One patient in dose level 2 had a 
      dose-limiting toxicity: grade 3 rash and grade 3 increase in 
      gamma-glutamyltransferase during combination therapy. Mean PF-3512676 half-life 
      ranged from 4.8 to 21.6 h (longer with higher doses). Four (33%) patients had 
      objective responses (one complete response, three partial responses), and seven 
      (58%) patients achieved stable disease. PF-3512676 as monotherapy and in 
      combination with chemotherapy had an acceptable safety profile in Japanese 
      patients with treatment-naive NSCLC.
FAU - Yamada, Kazuhiko
AU  - Yamada K
AD  - Department of Internal Medicine, National Cancer Center Hospital, Tokyo, Japan.
FAU - Nakao, Masao
AU  - Nakao M
FAU - Fukuyama, Chikara
AU  - Fukuyama C
FAU - Nokihara, Hiroshi
AU  - Nokihara H
FAU - Yamamoto, Noboru
AU  - Yamamoto N
FAU - Sekine, Ikuo
AU  - Sekine I
FAU - Kunitoh, Hideo
AU  - Kunitoh H
FAU - Ohe, Yuichiro
AU  - Ohe Y
FAU - Ohki, Emiko
AU  - Ohki E
FAU - Hashimoto, Junichi
AU  - Hashimoto J
FAU - Tamura, Tomohide
AU  - Tamura T
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090914
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (ProMune)
RN  - 0 (Toll-Like Receptor 9)
RN  - BG3F62OND5 (Carboplatin)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Carboplatin/administration & dosage
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Oligodeoxyribonucleotides/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - Paclitaxel/administration & dosage
MH  - Toll-Like Receptor 9/*antagonists & inhibitors
EDAT- 2009/10/22 06:00
MHDA- 2010/03/31 06:00
CRDT- 2009/10/22 06:00
PHST- 2009/10/22 06:00 [entrez]
PHST- 2009/10/22 06:00 [pubmed]
PHST- 2010/03/31 06:00 [medline]
AID - CAS1361 [pii]
AID - 10.1111/j.1349-7006.2009.01361.x [doi]
PST - ppublish
SO  - Cancer Sci. 2010 Jan;101(1):188-95. doi: 10.1111/j.1349-7006.2009.01361.x. Epub 
      2009 Sep 14.