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The role of hyperthermia in regional alkylating agent chemotherapy.

Publication ,  Journal Article
Abdel-Wahab, OI; Grubbs, E; Viglianti, BL; Cheng, T-Y; Ueno, T; Ko, S; Rabbani, Z; Curtis, S; Pruitt, SK; Dewhirst, MW; Tyler, DS
Published in: Clin Cancer Res
September 1, 2004

The role of hyperthermia during regional alkylating agent chemotherapy is controversial. The aim of this study was to determine the exact contribution of hyperthermia to tumor response during isolated limb infusion with l-phenylalanine mustard. Rats bearing rodent fibrosarcoma on the hindlimb underwent isolated limb infusion with saline, saline plus heat, l-phenylalanine mustard, l-phenylalanine mustard under conditions of normothermia, or l-phenylalanine mustard plus hyperthermia. Heat was administered locally using an in-line hot water circulation loop. Treatment with l-phenylalanine mustard at a concentration of 15 or 50 micrograms/mL was ineffective at producing tumor growth delay (P = 0.24 and 0.41, respectively). Furthermore, thermal enhancement of l-phenylalanine mustard activity was not seen at 15 micrograms/mL. However, administration of high-dose l-phenylalanine mustard, 50 micrograms/mL, with increasing amounts of heat yielded increasing tumor growth delay, increased regressions, and decreased proliferative index. Although l-phenylalanine mustard infusion under normothermia yielded a tumor growth delay of 7.1 days, combination l-phenylalanine mustard + hyperthermia treatment produced tumor growth delay of 27.0 days (P < 0.01; with two of five animals showing a complete response). Four hours after isolated limb infusion, 50.9% of cells in tumor treated with l-phenylalanine mustard + hyperthermia experienced apoptosis, whereas only 18.1, 16, and 4.4% of cells underwent apoptosis after treatment with l-phenylalanine mustard, saline + hyperthermia, or saline. The mean concentration of l-phenylalanine mustard within tumor relative to perfusate following isolated limb infusion was found to be similar among all groups at 0.023, 0.025, and 0.032 in animals undergoing isolated limb infusion with l-phenylalanine mustard, l-phenylalanine mustard + normothermia, and l-phenylalanine mustard + hyperthermia, respectively. These data indicate a synergistic cytotoxic effect of l-phenylalanine mustard + hyperthermia in isolated limb infusion, which is not attributable to enhanced tumor drug uptake.

Duke Scholars

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

September 1, 2004

Volume

10

Issue

17

Start / End Page

5919 / 5929

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Sarcoma, Experimental
  • Rats, Wistar
  • Rats
  • Oncology & Carcinogenesis
  • Melphalan
  • Hyperthermia, Induced
  • Fibrosarcoma
  • Female
  • Extremities
 

Citation

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Abdel-Wahab, O. I., Grubbs, E., Viglianti, B. L., Cheng, T.-Y., Ueno, T., Ko, S., … Tyler, D. S. (2004). The role of hyperthermia in regional alkylating agent chemotherapy. Clin Cancer Res, 10(17), 5919–5929. https://doi.org/10.1158/1078-0432.CCR-04-0096
Abdel-Wahab, Omar I., Elizabeth Grubbs, Benjamin L. Viglianti, Tsung-Yen Cheng, Tomio Ueno, SaeHee Ko, Zahid Rabbani, et al. “The role of hyperthermia in regional alkylating agent chemotherapy.Clin Cancer Res 10, no. 17 (September 1, 2004): 5919–29. https://doi.org/10.1158/1078-0432.CCR-04-0096.
Abdel-Wahab OI, Grubbs E, Viglianti BL, Cheng T-Y, Ueno T, Ko S, et al. The role of hyperthermia in regional alkylating agent chemotherapy. Clin Cancer Res. 2004 Sep 1;10(17):5919–29.
Abdel-Wahab, Omar I., et al. “The role of hyperthermia in regional alkylating agent chemotherapy.Clin Cancer Res, vol. 10, no. 17, Sept. 2004, pp. 5919–29. Pubmed, doi:10.1158/1078-0432.CCR-04-0096.
Abdel-Wahab OI, Grubbs E, Viglianti BL, Cheng T-Y, Ueno T, Ko S, Rabbani Z, Curtis S, Pruitt SK, Dewhirst MW, Tyler DS. The role of hyperthermia in regional alkylating agent chemotherapy. Clin Cancer Res. 2004 Sep 1;10(17):5919–5929.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

September 1, 2004

Volume

10

Issue

17

Start / End Page

5919 / 5929

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Sarcoma, Experimental
  • Rats, Wistar
  • Rats
  • Oncology & Carcinogenesis
  • Melphalan
  • Hyperthermia, Induced
  • Fibrosarcoma
  • Female
  • Extremities