Disease relevance of leucovorin

• Phase I-II trial of high-dose calcium leucovorin and 5-fluorouracil in advanced colorectal cancer [1].
• Incorporation of s.c. calcium leucovorin administration 16 h after each dose of 10EDAM and cis-Pt allowed a 4-fold increase in dosage of 10-EDAM without an increase in toxicity, increased median survival by an additional 120%, and quadrupled the number of tumor-free, long-term survivors to 40% of treated animals [2].
• Effective initial therapy of advanced breast cancer with fluorouracil and high-dose, continuous infusion calcium leucovorin [3].
• These results appear to suggest that 10EDAM with cis-Pt may have considerable potential for intracavitary therapy of human cancer, including ovarian carcinoma, particularly when incorporating delayed systemic calcium leucovorin administration [2].
• Phase I and pharmacokinetic study of recombinant human granulocyte-macrophage colony-stimulating factor given in combination with fluorouracil plus calcium leucovorin in metastatic gastrointestinal adenocarcinoma [4].

High impact information on leucovorin

• Those with more than 1 cm(3) residual tumor were randomly assigned to receive an additional five cycles of VACP or five cycles of vinblastine, methotrexate with calcium leucovorin rescue, and fluorouracil (VbMF) [5].
• In this Phase I study, the maximally tolerated doses (MTDs) of i.p. iododeoxyuridine (IdUrd) alone and in combination with i.v. calcium leucovorin (LV) were determined [6].
• Serum and cerebrospinal fluid distribution of 5-methyltetrahydrofolate after intravenous calcium leucovorin and intra-Ommaya methotrexate administration in patients with meningeal carcinomatosis [7].
• Although there was a difference in the time course for recovery in small intestine at each dosage of calcium leucovorin, the recovery of DNA synthesis as drug levels approached the dihydrofolate reductase content was similar in magnitude [8].
• Because of serious infections (fever larger than or equal to 101 degrees F. granulocytes less than 1,000/mm, 3 and hospitalization) and 1 drug death in the first 4 patients, oral calcium leucovorin, 20 to 30 mg/m2 orally, was given 2 days after methotrexate in subsequent treatment cycles [9].

Chemical compound and disease context of leucovorin

• To minimise toxicity, trimetrexate must be coadministered with calcium folinate (leucovorin calcium), a reduced folate coenzyme, which is transported into, and protects, mammalian host cells but not P. carinii cells [10].
• This study was conducted to determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration ratio (UFT; Bristol-Myers Squibb, Wallingford, CT) plus oral calcium leucovorin in the treatment of patients with advanced hepatocellular carcinoma (hepatoma) [11].
• Thirteen patients with primary lymphoma of the central nervous system (CNS) were treated with high-dose intravenous methotrexate (MTX), 3.5 gm/sq m, followed by calcium leucovorin rescue, at 3-week intervals, for three cycles [12].
• Eleven patients with Hodgkin's disease refractory to chemotherapy were treated with six cycles of intermediate-dose methotrexate with calcium leucovorin rescue, followed by cyclophosphamide, doxorubicin, vincristine, and prednisone (MTX-CHOP) [13].
• Phase II and III clinical trials have found oxaliplatin combined with fluorouracil/calcium folinate (leucovorin/folinic acid) to be an effective first- and second-line treatment for patients with metastatic colorectal cancer [14].

Biological context of leucovorin

• The onset of the central nervous system toxicity was acute with slurred speech, paresis of the external rectus eye muscles, ataxia, and hemiparesis, and symptoms resolved completely after 30 hours by treatment with calcium leucovorin and forced diuresis [15].
• We conducted a randomized trial to compare the pharmacokinetics/pharmacodynamics of two doses of calcium folinate [16].
• Neither clearance nor bioavailability of 1954U89 in dogs was affected significantly by administration of calcium leucovorin [17].
• Disposition of 5-formyl- and 5-methyltetrahydrofolic acid in serum after i.v. bolus of calcium folinate: pharmacokinetic drug interaction with preadministered interferon-alpha-2b [18].

Anatomical context of leucovorin

• Differential calcium leucovorin protection of human lymphoid cell lines from methotrexate [19].
• Moreover, calcium folinate ingested prior to chemotherapy totally prevented damage to the small intestinal mucosa induced by MTX, as assessed by the SBT in concert with structural, and biochemical indices [20].
• A phase II survival comparison of patients with adenocarcinoma of the pancreas treated with 5-fluorouracil and calcium leucovorin versus a matched tumor registry control population [21].
• The influence of calcium leucovorin on the co-trimoxazole induced inhibition of leukocyte regeneration after bone marrow transplantation in mice [22].

Associations of leucovorin with other chemical compounds

• Patients received 5-fluorouracil (375mg/m2/day x 5days) and calcium leucovorin (20mg/m2/day x 5days), q4weeks, two courses before and two courses after radiotherapy [23].
• AIM: To compare the effect, adverse events, cost-effectiveness and dose intensity (DI) of oral Xeloda vs calcium folinate (CF)/5-FU combination chemotherapy in patients with advanced gastrointestinal malignancies, both combined with bi-platinu two-way chemotherapy [24].
• A remarkable 81% of CFS patients experienced subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9, leucovorin) [25].

Gene context of leucovorin

• Twenty six patients with pleural mesothelioma of UICC stage I-IV excluding M1 disease (46% of whom had stage I disease and 38% stage III disease) were treated intravenously with high dose MTX (3 g) and calcium folinate rescue three times at intervals of 2 weeks and three times at intervals of 3 weeks [26].

Analytical, diagnostic and therapeutic context of leucovorin

• It appears to be particularly advantageous (in terms of response rate and duration of progression-free survival) when used in combination with fluorouracil/calcium folinate as both a first- and second-line option, although preliminary studies have failed to show any survival advantage over fluorouracil/calcium folinate alone [14].
• An impurity present in calcium folinate (N5-formyl-5,6,7,8-tetrahydrofolic calcium salt) active pharmaceutical ingredient (API) was detected by high-performance liquid chromatography (HPLC) [27].
• METHODS: Twenty-five patients (mean age: 62 years) receiving a 5-FU bolus plus continuous infusion with calcium leucovorin over 48 h and with normal pre-treatment cardiac physical examinations, ECG and echocardiography were enrolled [28].
• The two diastereoisomers of calcium folinate were analyzed separately by chiral HPLC to account for differences in their pharmacokinetics [16].
• After premedication, patients received paclitaxel as a 3-hour IV infusion (175 mg/m2) on day 1; UFT was administered orally at 300 mg/day (dose level 1), 400 mg/day (dose level 2), 500 mg/day (dose level 3), or 600 mg/day (dose level 4) in combination with 90 mg/day of calcium folinate in three divided doses for 14 days [29].

References