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

Ann Surg. 2012 Feb;255(2):281-6. doi: 10.1097/SLA.0b013e318242ebe7.

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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Tumor Necrosis Factor-alpha
  • Melphalan