Initial clinical study with N-(phosphonacetyl)-L-aspartic acid (PALA) in patients with advanced cancer.
Thirty-seven patients with inoperable malignancies were given 75 courses of N-(phosphonaceteyl)-L-aspartic acid (PALA). Twenty-seven of these patients received PALA as a continuous iv infusion over 24 hours at dose levels ranging from 500 to 10,500 mg/m2 of estimated body surface area. In addition, ten patients were given PALA by continuous iv infusion over 120 hours at total doses ranging from 4000 t0 8700 mg/m2. The dose-limiting toxic effects occurred in the skin (erythema, vesiculation, and bullae) and gastrointestinal mucosa (oral pain, cheilosis, oral mucosal ulceration, diarrhea, and hematochezia). Toxic reactions seemed more pronounced in patients with third-space fluid compartments. Myelosuppression was severe only in patients with pre-existing marrow dysfunction from neoplastic infiltration. No renal, hepatic, cardiac, or neurologic toxicity was seen. No cumulative toxic effects were evident in 14 patients who received repeated courses of PALA at 21-day intervals. For patients without third-space fluid, 8700 mg/m2/24 hours or 6500 mg/m2/120 hours were well-tolerated doses. One patient with chondrosarcoma had a partial response lasting 5 months.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced; D003875:Drug Eruptions / Q000209:etiology; D004341:Drug Evaluation; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects; D006801:Humans; D007263:Infusions, Parenteral; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009943:Organophosphorus Compounds; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid