TNF-alpha and doxorubicin in hyperthermic perfusion for limb sarcomas (phase I-II study): Preliminary results

C. R. Rossi, M. Foletto, A. Vecchiato, F. Di Filippo, M. Vaglini, M. Santinami, A. Azzarelli, R. Cavaliere, N. Cascinelli, M. Lise

Research output: Contribution to journalArticlepeer-review

Abstract

The end point of this study was to establish the Maximum Tolerable Dose (MTD) of TNF-alpha combined with doxorubicin in Hyperthermic Antiblastic Perfusion (HAP) as a neo-adjuvant treatment for patients with limb sarcoma, who are candidates for amputation. A further aim was to ascertain the activity of this regimen. Fourteen patients, subdivided into triplets, were perfused for 90 minutes with escalating doses (for each triplet) of TNF- alpha (0.5-3.3 mg) and standard doses of doxorubicin (bolus 0.7-1.4 mg/kg) at a tumor temperature of at least 41°C. Tumor response (necrosis) was assessed both histologically and radiologically. Systemic toxicity was hematological WHO grade II in 5 patients (in 1 it was associated with grade IV renal toxicity), hepatic grade II in 3 (1 with alopecia); two patients had alopecia only. Loco-regional toxicity (graded according to Wieberdink) was GI-II in 6 patients, GIII in 5 and GIV in 3. Tumor necrosis was evaluated in 8 patients, all of which scored more than 70%, histological necrosis being 100% in 3. Limb-sparing surgery was feasible in 6 (66%) out of 9 patients who underwent tumor resection. At present, all the patients are alive, 2 with pulmonary metastases, and so far none has developed local recurrence. Our findings suggest that TNF-alpha combined with doxorubicin in HAP seems to be quite well tolerated and highly active against limb sarcoma, even at low TNF-alpha doses, although the MTD of TNF-alpha has not yet been established.

Original languageEnglish
Pages (from-to)151-155
Number of pages5
JournalRegional Cancer Treatment
Volume9
Issue number3
Publication statusPublished - 1996

Keywords

  • Doxorubicin
  • Hyperthermia
  • Limb perfusion
  • Soft tissue sarcoma
  • TNF-alpha

ASJC Scopus subject areas

  • Oncology
  • Pharmacology

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