PMID- 19815483
OWN - NLM
STAT- MEDLINE
DCOM- 20100513
LR  - 20201212
IS  - 1938-0682 (Electronic)
IS  - 1558-7673 (Linking)
VI  - 7
IP  - 3
DP  - 2009 Oct
TI  - Safety and efficacy of PF-3512676 for the treatment of stage IV renal cell 
      carcinoma: an open-label, multicenter phase I/II study.
PG  - E58-65
LID - 10.3816/CGC.2009.n.025 [doi]
AB  - PURPOSE: Single-agent PF-3512676 (agatolimod), a Toll-like receptor 9 agonist, 
      was examined in an open-label, single-arm, multicenter phase I/II study to 
      determine its maximum tolerated dose (MTD), safety profile, antitumor activity, 
      pharmacokinetics, and immunologic effects in patients with advanced metastatic 
      renal cell carcinoma (RCC). PATIENTS AND METHODS: PF-3512676 was administered 
      subcutaneously weekly for up to 24 weeks to 39 adults with stage IV RCC. Patients 
      were excluded if they had received previous therapy other than surgery. Phase I 
      dose escalation began at 0.08 mg/kg, with phase II expansion to 20 patients to 
      estimate objective response rates at 0.16 mg/kg. Doses were subsequently 
      escalated to 0.81 mg/kg according to the phase I design. RESULTS: An MTD was not 
      reached. One patient who received 0.54 mg/kg had dose-limiting toxicities (grade 
      3 nonhematologic adverse events [AEs], including anorexia). The most commonly 
      reported AEs were flu-like symptoms and local injection-site reactions of 
      mild-to-moderate severity. The most commonly reported serious AE was grade 3 
      fatigue in 4 patients (10%). Grade 4 AEs included anemia, exacerbated dyspnea, 
      and polyarthralgia in 1 patient each. Two patients (5%), 1 each in the 0.16-mg/kg 
      and 0.54-mg/kg cohorts, achieved a partial response. Both responses were durable 
      (35 and 40 months). CONCLUSION: This was the first study to examine PF-3512676 
      safety and antitumor activity in patients with advanced RCC. Single-agent 
      treatment was tolerable. At the doses tested, PF-3512676 had modest antitumor 
      activity. Additional studies in combination with other agents or at higher 
      monotherapy doses might be warranted.
FAU - Thompson, John A
AU  - Thompson JA
AD  - Division of Medical Oncology, University of Washington, Seattle, WA, USA. 
      jat@u.washington.edu
FAU - Kuzel, Timothy
AU  - Kuzel T
FAU - Drucker, Beverly J
AU  - Drucker BJ
FAU - Urba, Walter J
AU  - Urba WJ
FAU - Bukowski, Ronald M
AU  - Bukowski RM
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Genitourin Cancer
JT  - Clinical genitourinary cancer
JID - 101260955
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (ProMune)
RN  - 0 (TLR9 protein, human)
RN  - 0 (Toll-Like Receptor 9)
SB  - IM
MH  - Adult
MH  - Antineoplastic Agents/adverse effects/pharmacokinetics/*therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/pathology
MH  - Chemotherapy, Adjuvant
MH  - Female
MH  - Humans
MH  - Kidney Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Oligodeoxyribonucleotides/administration & dosage/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Toll-Like Receptor 9/agonists
MH  - Treatment Outcome
EDAT- 2009/10/10 06:00
MHDA- 2010/05/14 06:00
CRDT- 2009/10/10 06:00
PHST- 2009/10/10 06:00 [entrez]
PHST- 2009/10/10 06:00 [pubmed]
PHST- 2010/05/14 06:00 [medline]
AID - S1558-7673(11)70032-5 [pii]
AID - 10.3816/CGC.2009.n.025 [doi]
PST - ppublish
SO  - Clin Genitourin Cancer. 2009 Oct;7(3):E58-65. doi: 10.3816/CGC.2009.n.025.