N-(phosphonacetyl)-L-aspartate and calcium leucovorin modulation of fluorouracil administered by constant rate and circadian pattern of infusion over 72 hours in metastatic gastrointestinal adenocarcinoma
| Autor: | Frank Grollman, J M Hamilton, Jean L. Grem, Lorrin K. Yee, Chris H. Takimoto, Carmen J. Allegra, C. Chabuk, Alice P. Chen, M. Grabenc, Barbara Schuler |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Phosphonoacetic Acid medicine.medical_specialty medicine.medical_treatment Leucovorin Pharmacology Adenocarcinoma Pharmacokinetics Internal medicine Infusion Procedure Antineoplastic Combined Chemotherapy Protocols medicine Aspartate Carbamoyltransferase Humans Circadian rhythm Infusions Intravenous Aged Gastrointestinal Neoplasms Leucovorin Calcium Chronotherapy Gastrointestinal tract Chemotherapy Aspartic Acid business.industry Hematology Middle Aged Endocrinology Oncology Fluorouracil Toxicity Female business medicine.drug |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 12(11) |
| ISSN: | 0923-7534 |
| Popis: | Background: We have reported that N-(phosphonacetyl)-L-aspartic acid (PALA) 1266 mg/m 2 can safely be given 24 hours prior to the start of a 72-hour infusion of fluorouracil (FUra) and leucovorin (LV) at doses of 2000 and 500 mg/m 2 /day. Since inhibition of aspartate carbamoyltransferase (ACTase) activity was evident 4 hours post PALA, we wished to evaluate PALA given 1 hour prior to FUra. Further, we studied the toxicity and pharmacokinetics with FUra given by either fixed-or variable-rate infusion. Patients and methods: Twenty-seven patients with gastrointestinal tract adenocarcinomas were treated with PALA 1266 mg/m 2 /15 min followed by a 72-hour infusion of FUra and LV (1750 & 500 mg/m 2 /day) given by fixed- or variable-rate (peak at 4:00 A.M.). Results: Clinical toxicity was similar in two consecutive cycles in 17 patients receiving fixed- and variable-rate infusion at the same FUra dose. Overall, grade 3 stomatitis and hand-foot syndrome occurred in 12% and 4% patients receiving fixed- and in 16% and 10.5% of patients receiving variable-rate infusions. Six of 24 evaluable patients (25%) had a partial response. The profile of FUra plasma levels (Cp) over a 24-hour period during fixed- and variable-rate infusions were strikingly different, but the average Cp and area under the concentration-time curves were comparable. ACTase activity was significantly decreased at 4 and 24 hours after PALA (12% and 18% of baseline; P < 0.001), but enzyme activity had recovered to 40% by 72 hours. Conclusions: This regimen was active and well tolerated with similar toxicities with FUra given by either fixed- or variable rate infusion. PALA 1266 mg/m 2 significantly inhibited ACTase activity for at least 24 hours. |
| Databáze: | OpenAIRE |
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