A phase II trial of PALA + dipyridamole in patients with advanced soft-tissue sarcoma

• Published in: Cancer chemotherapy and pharmacology 1991, Vol.28 (1), p.51-54
• Main Authors: CASPER, E. S, BASELGA, J, SMART, T. B, MAGILL, G. B, MARKMAN, M, RANHOSKY, A
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - blood; Antineoplastic Agents - therapeutic use; Aspartic Acid - administration & dosage; Aspartic Acid - adverse effects; Aspartic Acid - analogs & derivatives; Aspartic Acid - blood; Aspartic Acid - therapeutic use; Biological and medical sciences; Chemotherapy; Dipyridamole - administration & dosage; Dipyridamole - adverse effects; Dipyridamole - blood; Dipyridamole - therapeutic use; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Phosphonoacetic Acid - administration & dosage; Phosphonoacetic Acid - adverse effects; Phosphonoacetic Acid - analogs & derivatives; Phosphonoacetic Acid - blood; Phosphonoacetic Acid - therapeutic use; Sarcoma - blood; Sarcoma - drug therapy; Soft Tissue Neoplasms - blood; Soft Tissue Neoplasms - drug therapy
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/BF00684956

A total of 21 patients with advanced soft tissue sarcoma enrolled in a phase II trial of 3.5 g/m2 N-phosphonacetyl-L-aspartate (PALA) given intravenously every 3 weeks plus 50 mg/m2 dipyridamole (Persantine) given orally every 6 h. Dipyridamole administration was initiated 1 week before the first dose of PALA. Peak and trough plasma concentrations of dipyridamole were measured before and after the first dose of PALA in 14 patients. In all, 19 patients were evaluable for therapeutic response. One subject experienced partial regression of a pulmonary metastasis; no other major response was observed. Diarrhea was the most prominent toxicity; in one patient it was life-threatening and was associated with a severe rash. On the day preceding PALA administration, the median peak plasma concentration of dipyridamole was 2,208 ng/ml and the median trough value was 904 ng/ml. Similar values were obtained on the day of PALA administration. Although the levels achieved were similar to those required to modulate the activity of PALA in preclinical systems, the therapeutic results obtained in the present study were not superior to those reported for PALA alone in previously treated patients with soft-tissue sarcoma.