Liposomal doxorubicin with and without TNFalpha in the perfusional treatment of advanced soft tissue limb sarcoma: preliminary results.
BACKGROUND
A combination of doxorubicin and tumor necrosis factor alpha (TNFalpha) has been proven to be very effective in the perfusional treatment of advanced soft tissue limb sarcoma both in terms of tumor necrosis and limb conservative surgery rate. Unfortunately, in some patients a grade IV limb reaction has been recorded. The key solution might be the use of liposomal doxorubicin (Caelyx) because the carrier seems to release the drug preferentially in the tumor rather than in the healthy tissue.


METHODS
Twenty patients were treated with Caelyx: 14 with Caelyx alone and 6 in combination with a low TNFalpha dose (1 mg). In the first series of 14 patients a dose escalation study was carried out starting from a dose of 10 mg/L of limb volume. Six patients were treated with Caelyx (16 mg) and TNFalpha (1 mg).


RESULTS
The maximum tolerated dose (MTD) was 16 mg/L as in two patients treated with 18 mg/L a grade IV limb reaction was observed. Tumor response was satisfactory and conservative surgery was carried out in 13 patients. In 6 patients treated with Caelyx and TNFalpha, only a grade I limb reaction was recorded, thus, confirming that TNFalpha did not increase toxicity, at least at a dose of 1 mg. The Caelyx-TNFalpha combination did increase treatment efficacy. Tumor necrosis > or = 70% was observed in 4 out of 6 patients, one with 100% necrosis (pathological complete response). All the patients underwent conservative surgery.


CONCLUSIONS
The Caelyx-TNFalpha combination was proven to increase the efficacy of Caelyx alone, with a very low toxicity. These preliminary results have to be tested in a larger patient population.
Di Filippo
Franco
F
Department of Surgery, Regina Elena National Cancer Institute, Rome, Italy. difilippo@ifo.it
Anzà
Michele
M
Garinei
Rosa
R
Cavaliere
Francesco
F
Perri
Pasquale
P
Botti
Claudio
C
Di Angelo
Piera
P
Di Filippo
Simona
S
Maini
Carlo Ludovico
CL
Pasqualoni
Rossella
R
Di Segni
Susanna
S
Colantonio
Simona
S
Bruno
Pietro
P
Piarulli
Loredana
L
Principi
Francesca
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D010478:Chemotherapy, Cancer, Regional Perfusion; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage
D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin