Weekly 5-fluorouracil combined with PALA: toxic and therapeutic effects in colorectal cancer.
A total of 51 patients (eight previously treated) received PALA added to 5-fluorouracil (5FU) given weekly. After 32 patients, the PALA schedule was changed from every other week to weekly, 24 hours preceding 5FU in accordance with preclinical leads (see text). Both schedules were associated with moderately severe toxic effects related primarily to PALA (skin rash) or to the combined effects of both drugs (diarrhea, vomiting, conjunctivitis, and neurotoxicity). Overall nine partial responses were observed, including three in patients previously treated with 5FU. However, future studies with this combination utilizing the current or other previously published schedules are not warranted in colorectal cancer. Since toxicity is a prominent impediment, the possibility of therapeutic synergy may perhaps be explored at drastically reduced doses of PALA, combined with other modulating measures.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D002493:Central Nervous System Diseases / Q000139:chemically induced; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010746:Phosphonoacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D010865:Pilot Projects; D012004:Rectal Neoplasms / Q000188:drug therapy*
D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid; D005472:Fluorouracil