Hyperthermic pelvic perfusion with tumor necrosis factor-α for locally advanced cancers: encouraging results of a phase II study.

Abstract

PURPOSE:

To assess the efficacy of isolated pelvic perfusion (IPP) with tumor necrosis factor (TNF)-α and melphalan in patients with locally advanced cancers in the pelvic and groin area requiring mutilating surgery.

METHODS:

A total of 27 patients were enrolled (carcinoma, n = 17; sarcoma/melanoma, n = 4; and endocrine tumor, n = 6). They were candidates for exarticulation (n = 3) or exenteration (n = 11) or were judged unresectable (n = 13). In installing IPP, tourniquets were positioned around both thighs, and an inflated pressure suit was placed at a subthoracic position. Tumor necrosis factor-α (300 μg) was injected in the perfusate, followed 5 minutes later by melphalan at 1.5 mg/kg. After 30 minutes, the remaining drugs were washed out. Leakage was assessed with technetium Tc 99m radiolabeled human serum albumin, and a pharmacokinetic study was performed. Efficacy was based on the complete response rate observed on magnetic resonance imaging.

RESULTS:

Pelvic/systemic ratios of melphalan/TNF/technetium Tc 99m were 14.2/7/3.6. Responses on magnetic resonance imaging were as follows: 30% complete, 30% partial, 19% no change, and 15% progression. Two patients were not evaluable because they did not receive the treatment. Pre-IPP/post-IPP median percentage of necrosis on magnetic resonance imaging was 10%/70%. Median follow-up was 43 months. Median overall survival was 17 months. Twelve-month survival rate, disease-free survival, and local and metastatic recurrence rates were 67%, 30%, 57%, and 26%, respectively.

CONCLUSIONS:

Isolated pelvic perfusion with TNF-α compares favorably with historical data, as it was observed in limb perfusion and could provide a chance to translate its successful combination with chemotherapy into treatment of locally advanced pelvic cancers.

• Authors: Sylvie Bonvalot, Thierry de Baere, Jean Mendiboure, Angelo Paci, Françoise Farace, Laurence Drouard-Troalen, Laure Bonnet, Antoine Hakime, Guillaume Bonniaud, Bruno Raynard, Philippe Israel, Axel Le Cesne, Alexander M Eggermont, Agnès Laplanche, Jane Muret
• Journal: Annals of surgery (Ann Surg) Vol. 255 Issue 2 Pg. 281-6 (Feb 2012) ISSN: 1528-1140 [Electronic] United States
• PMID: 22241290 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Necrosis Factor-alpha
• Melphalan

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (pharmacokinetics, therapeutic use)
• Chemotherapy, Cancer, Regional Perfusion (methods)
• Disease-Free Survival
• Endocrine Gland Neoplasms (drug therapy, mortality)
• Female
• Humans
• Hyperthermia, Induced
• Kaplan-Meier Estimate
• Magnetic Resonance Imaging
• Male
• Melanoma (drug therapy, mortality)
• Melphalan (administration & dosage, pharmacokinetics)
• Middle Aged
• Pelvic Neoplasms (drug therapy, mortality)
• Recurrence
• Sarcoma (drug therapy, mortality)
• Survival Rate
• Treatment Outcome
• Tumor Necrosis Factor-alpha (administration & dosage, pharmacokinetics)