Can interleukin-2 reverse anthracyclin chemoresistance in metastatic soft tissue sarcoma patients. Results of a prospective phase II clinical trial.
Anthracyclin-based chemotherapy is the most efficient chemotherapy for advanced or metastatic soft tissue sarcoma (STS). Development of anthracyclin chemoresistance has been widely documented. In a previous clinical trial, we evaluated a possible reversal of anthracyclin chemoresistance after exposure to subcutaneous IL-2. The current phase II clinical study entered 17 proven metastatic STS patients, refractory to anthracyclin chemotherapy, who received IL-2, and subsequent anthracyclin-based chemotherapy. Subcutaneous IL-2 was administered at 18 million Units/day, 5 days a week for two consecutive weeks. Treatment was administered safely at the full dose for 16 out of 17 patients, and toxicity was mild. One patient had treatment stopped because of rapidly progressive disease. As soon as patients met biological and clinical criteria, chemotherapy was administered. The median delay was 12 days (2-23) from the end of IL-2 administration. Only 13 patients received anthracyclin chemotherapy after IL-2. The other 4 patients did not receive chemotherapy for progressive disease. One partial response was observed out of 13 evaluable patients (7.7% overall response, 95% confidence interval: 0.2 to 36). The overall response rate was 5.9% (95% CI: 0.15 to 29), so the study was stopped due to lack of efficacy. In previous and current studies, a few patients have developed restored anthracyclin chemosensitivity following exposure to IL-2. No conclusive evidence of IL-2 chemoresistance reversal was obtained from this study. Further investigations need to be performed with perhaps a larger group of more carefully selected patients using a different schedule and sequence of combined cytokines and chemotherapy.
Gravis
G
G
Oncology Unit, Institut Paoli-Calmettes, 232, boulevard Sainte-Marguerite, 13273 Marseille Cedex 09, France.
Mousseau
M
M
Douillard
J Y
JY
Dorval
T
T
Fabbro
M
M
Escudier
B
B
Mignot
L
L
Viens
P
P
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D007376:Interleukin-2