PMID- 9108094
OWN - NLM
STAT- MEDLINE
DCOM- 19970522
LR  - 20240214
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 94
IP  - 8
DP  - 1997 Apr 15
TI  - Synergy of Taxol and radioimmunotherapy with yttrium-90-labeled chimeric L6 
      antibody: efficacy and toxicity in breast cancer xenografts.
PG  - 4000-4
AB  - Synergistic multimodality therapy is needed for breast cancer. Breast cancer 
      frequently has p53 mutations that result in cells less likely to undergo 
      apoptosis when exposed to DNA damaging therapies. Taxol (paclitaxel) is more 
      effective in the presence of mutant p53. (90)Y-labeled DOTA-peptide-ChL6 
      ((90)Y-ChL6, where ChL6 is chimeric L6 antibody and DOTA is 
      1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid) is a novel 
      radioimmunoconjugate for targeting radiation to cancer. It has a stable metal 
      chelator and a peptide linker that can be catabolized by hepatic lysozymes. This 
      study was designed to assess potential synergism between Taxol and (90)Y-ChL6 in 
      a highly anaplastic breast cancer model, HBT 3477. There was no tumor response in 
      mice receiving ChL6 or Taxol alone. In mice receiving (90)Y-ChL6 alone, 79% (15 
      of 19) of tumors responded although none were cured. If Taxol was administered 
      24-72 hours before (90)Y-ChL6, again, 79% (23 of 29) of tumors responded but 21% 
      were cured. When Taxol was administered 6 or 24 hours after (90)Y-ChL6, 100% (46 
      of 46) of tumors responded and 48% were cured. Taxol given with (90)Y-ChL6 did 
      not substantially increase toxicity. Enhancement of the therapeutic effect when 
      Taxol was added to (90)Y-ChL6 therapy for HBT 3477 xenografts was striking. The 
      synergistic therapeutic effect of Taxol with (90)Y-ChL6 may relate to the p53 
      mutant status and BCL2 expression in HBT 3477 cells, observations that increase 
      the likelihood that the results of this study are relevant to therapy for breast 
      cancer in patients. In conclusion, Taxol seemed to be synergistic with (90)Y-ChL6 
      in this human breast cancer model. Up to 50% of these anaplastic breast cancer 
      xenografts were cured by combined modality therapy.
FAU - DeNardo, S J
AU  - DeNardo SJ
AD  - Department of Internal Medicine, University of California Davis Medical Center, 
      Sacramento 95816, USA.
FAU - Kukis, D L
AU  - Kukis DL
FAU - Kroger, L A
AU  - Kroger LA
FAU - O'Donnell, R T
AU  - O'Donnell RT
FAU - Lamborn, K R
AU  - Lamborn KR
FAU - Miers, L A
AU  - Miers LA
FAU - DeNardo, D G
AU  - DeNardo DG
FAU - Meares, C F
AU  - Meares CF
FAU - DeNardo, G L
AU  - DeNardo GL
LA  - eng
GR  - P01 CA047829/CA/NCI NIH HHS/United States
GR  - R01 CA016861/CA/NCI NIH HHS/United States
GR  - CA16861/CA/NCI NIH HHS/United States
GR  - CA47829/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Antibodies)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Interleukin-6)
RN  - 0 (Yttrium Radioisotopes)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Antibodies/*administration & dosage
MH  - Antineoplastic Agents, Phytogenic/*administration & dosage
MH  - Breast Neoplasms/*therapy
MH  - Combined Modality Therapy
MH  - Female
MH  - Humans
MH  - Interleukin-6/*immunology
MH  - Mammary Neoplasms, Animal/*therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neoplasm Transplantation
MH  - Neoplasms, Experimental/*therapy
MH  - Paclitaxel/*administration & dosage
MH  - *Radioimmunotherapy
MH  - Transplantation, Heterologous
MH  - Yttrium Radioisotopes/*administration & dosage
PMC - PMC20557
EDAT- 1997/04/15 00:00
MHDA- 1997/04/15 00:01
PMCR- 1997/10/15
CRDT- 1997/04/15 00:00
PHST- 1997/04/15 00:00 [pubmed]
PHST- 1997/04/15 00:01 [medline]
PHST- 1997/04/15 00:00 [entrez]
PHST- 1997/10/15 00:00 [pmc-release]
AID - 0358 [pii]
AID - 10.1073/pnas.94.8.4000 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):4000-4. doi: 10.1073/pnas.94.8.4000.