Chemoimmunotherapy in conjunction with surgery: Strategies for management of murine neuroblastoma

Michael P. Leonard, John Phillip Gearhart, Robert D. Jeffs

Research output: Contribution to journalArticle

Abstract

The combination of biological response modifiers with cytotoxic drugs has proven to be synergistic in several tumor systems. Recombinant human tumor necrosis factor (rhTNF) has been shown to enhance the antitumor efficacy of etoposide (VP-16) in the treatment of C1300 murine neuroblastoma. However, after completion of therapy, tumor growth resumes and results in subsequent death. In an effort to assess the impact of combining surgery with rhTNF/VP-16 therapy, A J mice bearing the C1300 murine neuroblastoma were treated within adjuvant or neoadjuvant protocols. Adjuvant-treated animals had a longer interval to disease recurrence (P = .01) and smaller average recurrent tumor volumes postexcision (P <.05) compared with surgical controls. Histological evidence of tumor recurrence and liver metastases was seen in both adjuvant-treated and surgical control animals. Neoadjuvant-treated animals had a longer interval to disease recurrence (P = .03) and smaller average recurrent tumor volumes up to 14 days postexcision (P <.02) compared with surgical controls. In addition, 30% of the neoadjuvant-treated animals had no microscopic evidence of disease recurrence, and only 14% had histological evidence of liver metastases. The surgical controls in the neoadjuvant experiment all had histological evidence of disease recurrence and liver metastases. Thus, the combination of surgery and rhTNF/VP-16 in the adjuvant or neoadjuvant setting appears to significantly delay the progression of C1300 murine neuroblastoma. Furthermore, administering chemoimmunotherapy prior to surgical excision in a neoadjuvant manner appears to be most beneficial as regards prevention of local disease recurrence and distant metastases.

Original languageEnglish (US)
Pages (from-to)1224-1229
Number of pages6
JournalJournal of Pediatric Surgery
Volume26
Issue number10
DOIs
StatePublished - 1991

Fingerprint

Neuroblastoma
Etoposide
Recurrence
Neoplasm Metastasis
Tumor Burden
Neoplasms
Liver
Immunologic Factors
Liver Diseases
Therapeutics
Growth
Pharmaceutical Preparations
human TNF protein

Keywords

  • Chemoimmunotherapy, adjuvant, neoadjuvant
  • murine neuroblastoma

ASJC Scopus subject areas

  • Surgery

Cite this

Chemoimmunotherapy in conjunction with surgery : Strategies for management of murine neuroblastoma. / Leonard, Michael P.; Gearhart, John Phillip; Jeffs, Robert D.

In: Journal of Pediatric Surgery, Vol. 26, No. 10, 1991, p. 1224-1229.

Research output: Contribution to journalArticle

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abstract = "The combination of biological response modifiers with cytotoxic drugs has proven to be synergistic in several tumor systems. Recombinant human tumor necrosis factor (rhTNF) has been shown to enhance the antitumor efficacy of etoposide (VP-16) in the treatment of C1300 murine neuroblastoma. However, after completion of therapy, tumor growth resumes and results in subsequent death. In an effort to assess the impact of combining surgery with rhTNF/VP-16 therapy, A J mice bearing the C1300 murine neuroblastoma were treated within adjuvant or neoadjuvant protocols. Adjuvant-treated animals had a longer interval to disease recurrence (P = .01) and smaller average recurrent tumor volumes postexcision (P <.05) compared with surgical controls. Histological evidence of tumor recurrence and liver metastases was seen in both adjuvant-treated and surgical control animals. Neoadjuvant-treated animals had a longer interval to disease recurrence (P = .03) and smaller average recurrent tumor volumes up to 14 days postexcision (P <.02) compared with surgical controls. In addition, 30{\%} of the neoadjuvant-treated animals had no microscopic evidence of disease recurrence, and only 14{\%} had histological evidence of liver metastases. The surgical controls in the neoadjuvant experiment all had histological evidence of disease recurrence and liver metastases. Thus, the combination of surgery and rhTNF/VP-16 in the adjuvant or neoadjuvant setting appears to significantly delay the progression of C1300 murine neuroblastoma. Furthermore, administering chemoimmunotherapy prior to surgical excision in a neoadjuvant manner appears to be most beneficial as regards prevention of local disease recurrence and distant metastases.",
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