PMID- 7613644
OWN - NLM
STAT- MEDLINE
DCOM- 19950818
LR  - 20191031
IS  - 1067-5582 (Print)
IS  - 1067-5582 (Linking)
VI  - 17
IP  - 3
DP  - 1995 Apr
TI  - Combination therapy with ifosfamide and liposome-encapsulated muramyl tripeptide: 
      tolerability, toxicity, and immune stimulation.
PG  - 181-93
AB  - A phase IIb trial using liposome-encapsulated muramyl tripeptide 
      phosphatidylethanolamine (L-MTP-PE) in combination with ifosfamide (IFX) for 
      patients with relapsed osteosarcoma was undertaken to determine (a) the 
      tolerability of the combination therapy, (b) if L-MTP-PE increased the toxicity 
      of IFX, and (c) whether IFX altered or suppressed the in vivo immune response to 
      L-MTP-PE. Patients had histologically proven osteosarcoma and pulmonary 
      metastases that either developed during adjuvant chemotherapy or were present at 
      diagnosis, persisted despite chemotherapy, and recurred following surgical 
      excision. Stratum A patients were rendered clinically free of disease within 4 
      weeks of study entry prior to receiving combination therapy. IFX was administered 
      at 1.8 g/m2 for 5 days every 21 days for up to eight cycles. L-MTP-PE was 
      administered twice weekly for 12 weeks, then once weekly for 12 weeks. Once cycle 
      of combination therapy was defined as 5 days of IFX and 3 weeks of L-MTP-PE 
      therapy. Stratum B patients had measurable disease at study entry that was judged 
      to be amenable to surgical resection. Stratum B patients received three cycles of 
      combination therapy prior to surgery to judge clinical and histologic response. 
      Postoperatively, patients received an additional five cycles. A total of nine 
      patients were entered into the protocol: six on stratum A and three on stratum B. 
      Serial blood samples were collected and assayed for cytokine levels (tumor 
      necrosis factor-alpha [TNF alpha], interleukin-6 [IL-6], IL-8, neopterin, 
      C-reactive protein). In addition, peripheral blood monocyte tumoricidal activity 
      was evaluated pre- and post-combination therapy. Complete blood counts with 
      differential and platelet counts were followed weekly. No increase in the toxic 
      side effects of IFX was demonstrated when administered with L-MTP-PE nor were 
      delays in IFX administration due to neutropenia experienced. The toxic side 
      effects of L-MTP-PE were also not increased. Elevations of serum C-reactive 
      protein, plasma neopterin, IL-6, IL-8, and TNF alpha following combination 
      therapy were similar to those observed in patients treated with L-MTP-PE alone. 
      Monocyte-mediated tumoricidal activity was elevated 24 and 72 h following 
      L-MTP-PE and IFX therapy, similar to what has been reported following L-MTP-PE 
      alone. Tumor specimens obtained from stratum B patients showed the histologic 
      characteristics consistent with a "chemotherapy effect," i.e., dead, amorphous, 
      acellular osteoid with cell drop-out.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Kleinerman, E S
AU  - Kleinerman ES
AD  - Department of Cell Biology, University of Texas M.D. Anderson Cancer Center, 
      Houston 77030, USA.
FAU - Meyers, P A
AU  - Meyers PA
FAU - Raymond, A K
AU  - Raymond AK
FAU - Gano, J B
AU  - Gano JB
FAU - Jia, S F
AU  - Jia SF
FAU - Jaffe, N
AU  - Jaffe N
LA  - eng
GR  - CA16672/CA/NCI NIH HHS/United States
GR  - CA42992/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Immunother Emphasis Tumor Immunol
JT  - Journal of immunotherapy with emphasis on tumor immunology : official journal of 
      the Society for Biological Therapy
JID - 9418950
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Liposomes)
RN  - 0 (Phosphatidylethanolamines)
RN  - 1LM890Q4FY (mifamurtide)
RN  - 53678-77-6 (Acetylmuramyl-Alanyl-Isoglutamine)
RN  - UM20QQM95Y (Ifosfamide)
SB  - IM
MH  - Acetylmuramyl-Alanyl-Isoglutamine/administration & dosage/adverse 
      effects/*analogs & derivatives
MH  - Adjuvants, Immunologic/*administration & dosage
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*adverse effects
MH  - Child
MH  - Humans
MH  - Ifosfamide/*administration & dosage/adverse effects
MH  - Liposomes/administration & dosage
MH  - Lung Neoplasms/*drug therapy/immunology/pathology/secondary
MH  - Middle Aged
MH  - Osteosarcoma/*drug therapy/immunology/pathology
MH  - Phosphatidylethanolamines/*administration & dosage/adverse effects
EDAT- 1995/04/01 00:00
MHDA- 1995/04/01 00:01
CRDT- 1995/04/01 00:00
PHST- 1995/04/01 00:00 [pubmed]
PHST- 1995/04/01 00:01 [medline]
PHST- 1995/04/01 00:00 [entrez]
AID - 10.1097/00002371-199504000-00007 [doi]
PST - ppublish
SO  - J Immunother Emphasis Tumor Immunol. 1995 Apr;17(3):181-93. doi: 
      10.1097/00002371-199504000-00007.