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PubMed1991

Continuous infusion 5-fluorouracil with bolus adriamycin and mitomycin and low-dose cisplatin (FAMP) in the treatment of metastatic gastric carcinoma: an evaluation of efficacy and toxicity.

A pilot study was performed to evaluate the feasibility of administering prolonged continuous infusion 5-fluorouracil with multiple bolus chemotherapeutic agents. Twelve patients with advanced measurable gastric carcinoma were treated with a combination chemotherapy program of continuous infusion 5-fluorouracil, bolus Adriamycin, mitomycin C, and low-dose cisplatin (FAMP). Responses were observed in 5 patients (2 complete and 3 partial). Observed toxicities included leukopenia, thrombocytopenia, mucositis, and hand-foot syndrome. Although the FAMP regimen has activity in advanced gastric carcinoma, the number of patients evaluated was small and significant improvement over currently available regimens could not be demonstrated. Evaluation of toxicities indicates that bolus administration of multiple agents (specifically, Adriamycin, mitomycin C, and cisplatin) can be used in conjunction with continuously infused 5-fluorouracil without excessive toxicity.

Adult↗
PubMed1990

Folate nephropathy occurring during cytotoxic chemotherapy with high-dose folinic acid and 5-fluorouracil.

High-dose folinic acid with 5-fluorouracil (5-FU) is a novel combination chemotherapy used in the treatment of metastatic gastrointestinal cancer. One of the mechanisms of action of 5-FU is its conversion into fluorodeoxyuridylate (FdUMP), which inhibits thymidilate synthetase (TS). The rate of inhibition of TS is augmented by increasing concentrations of folinic acid. On the other hand, it is well known that treatment of animals with high doses of folinic acid results in acute renal failure due to tubular obstruction. In order to find out whether there are similar findings in the clinical setting, we investigated 8 patients (pts.) with metastatic gastrointestinal cancer who were treated with this chemotherapy. We used the following parameters: 1. excretion of four urinary enzymes (LDH, LAP, GGT, NAG); 2. creatinine clearance on days 1 and 5. Therapy consisted of folinic acid 200 mg/m2 i.v. on days 1-5 and 5-fluorouracil 400 mg/m2 on days 1-5. Each treatment cycle was repeated on day 28. We found a constant decrease in the excretion of all 4 enzymes from normal to subnormal values which was statistically significant (p less than .05) during the two treatment cycles. Creatinine clearance decreased about 50% in three patients from normal initial values. In conclusion, during therapy with high-dose folinic acid and 5-fluorouracil we found signs of tubular damage which are similar to those found in folate nephropathy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Oral tegafur-uracil plus folinic acid versus intravenous 5-fluorouracil plus folinic acid as adjuvant chemotherapy of colon cancer.

To compare, in terms of compliance, toxicity, quality of life (QOL) and efficacy, intravenous 5-fluorouracil plus folinic acid with oral tegafur-uracil plus folinic acid as postoperative adjuvant chemotherapy after curative resection in patients with Dukes' stage B2 and C2 colon cancer. Among all patients with adenocarcinoma of the colon operated on between July 1997 and June 1999, 122 with Dukes' stage B2 or C2 colon cancer were enrolled in this study. Fifty-three patients were treated with intravenous 5-fluorouracil plus folinic acid (5-FU group) and 69 with oral tegafur-uracil plus folinic acid (UFT group). Compliance, toxicity, QOL and efficacy were evaluated. Compared with the 5-FU group, patients in the UFT group experienced a lower incidence of grade 1 toxicity. The incidences of grade 2-4 toxicity were similar in the two treatment groups. However, severe toxicity (grade 3 or 4) was rare in both groups. A steady and significant increase of the QOL score, both during and after therapy, was evident in both groups suggesting that chemotherapy is quite tolerable and does not deteriorate the patients' QOL. At the median follow-up duration of 28 months, the survival rate and disease free survival rate for the UFT and 5-FU groups were 94.9% vs. 92.5% and 87.5% vs. 84.1%, respectively (p > 0.05). These data suggest that oral tegafur-uracil modulated with oral folinic acid as an adjuvant chemotherapy in patients with Dukes' stage B2 and C2 colon cancer may be a good alternative to infusional 5- fluorouracil.

Adenocarcinoma↗
PubMed1990

Continuous infusion high-dose leucovorin with 5-fluorouracil and cisplatin for untreated stage IV carcinoma of the head and neck.

STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck. DESIGN: Nonrandomized, prospective trial. SETTING: A comprehensive cancer center. PATIENTS: Thirty-five patients (4 patients [11%], stage III; 31 patients [89%], stage IV [MO]), all evaluable for response and toxicity. INTERVENTIONS: Two to three cycles of PFL before definitive, local-regional therapy (surgery and radiation therapy or radiation therapy alone). Chemotherapy included continuous intravenous infusion of cisplatin (25 mg/m2 body surface area daily, days 1 through 5); 5-fluorouracil (800 mg/m2 body surface area daily, days 2 through 6); and leucovorin (500 mg/m2 body surface area daily, days 1 through 6) administered once every 28 days. Pathologic response was evaluated by surgical resection or biopsy. Serum-reduced folates were measured before and 18 hours after the initiation of chemotherapy. RESULTS: A clinical response to PFL was achieved in 28 of 35 (80%) patients: 23 (66%) patients had a complete response (90% CI, 50% to 79%) and 5 (14%) patients, a partial response. A complete response was confirmed pathologically in 14 of 19 (74%) patients. The most common toxicity was mucositis (grade 2 to 3; 94% of patients). Dose reduction for toxicity was necessary in 11 (31%) patients. There were no treatment-related deaths. Serum levels of leucovorin and (6S)5-methyltetrahydrofolate were measured in 7 patients. After 18 hours, the mean leucovorin level (+/- SD) was 34.3 +/- 1.5 mumol/L, of which only 8.0 +/- 0.5% was the active 6S isomer. The mean serum (6S)5-methyltetrahydrofolate was 9.2 +/- 0.6 mumol/L. CONCLUSIONS: Continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin is a new and highly active chemotherapy regimen that can achieve clinical and pathologically confirmed complete responses in a substantial proportion of patients with advanced, local-regional squamous cell carcinoma of the head and neck. Further studies are needed to confirm the activity of PFL and to determine its potential impact on local tumor control and disease-free and overall survival.

Adult↗
PubMed1991

A new syndrome: ascites, hyperbilirubinemia, and hypoalbuminemia after biochemical modulation of fluorouracil with N-phosphonacetyl-L-aspartate (PALA)

OBJECTIVE: To report a new syndrome of ascites, hyperbilirubinemia, and hypoalbuminemia after treatment with N-phosphonacetyl-L-aspartate (PALA) and fluorouracil for metastatic colorectal cancer. DESIGN: Retrospective analysis. SETTING: Regional cancer treatment center. PATIENTS: Forty-four previously untreated patients with metastatic colorectal cancer in a phase I-II trial of PALA-fluorouracil. MEASUREMENTS AND MAIN RESULTS: One or more transient hepatic abnormalities frequently occurred in 15 of the 17 responding patients. Within the first 10 weeks of treatment, 5 patients developed ascites, 12 had a decrease in the serum albumin level, 6 developed bilirubin elevations, and 7 had transaminase elevations, all in the presence of a complete or partial tumor response. Prolongations of the prothrombin time and elevations of serum glucose levels were also seen. CONCLUSIONS: An unusual syndrome of ascites, hyperbilirubinemia, and hypoalbuminemia is associated with a PALA-fluorouracil regimen. These abnormalities, which may be related to decreased hepatic protein synthesis, occurred more often in patients whose tumor was responding to chemotherapy. Clinicians must recognize that in patients undergoing chemotherapy with these agents, ascites and elevated liver function tests may be secondary to drug administration and are not necessarily due to disease progression.

Aged↗
PubMed1995

Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report.

OBJECTIVE: To determine the effectiveness of two adjuvant therapy regimens in improving surgical cure rates in stage III (Dukes stage C) colon cancer. DESIGN: Randomized, concurrently controlled clinical trial. SETTING: Major cancer centers, universities, and community clinics affiliated with the North Cancer Treatment Group, the Southwest Oncology Group, and the Eastern Cooperative Oncology Group. PATIENTS: Those who had had curative-intent resections of stage III colon cancer in the previous 1 to 5 weeks. INTERVENTION: Patients were assigned to observation only, to levamisole alone (50 mg orally three times/d for 3 days, repeated every 2 weeks for 1 year), or to this regimen of levamisole plus fluorouracil (450 mg/m2 body surface area intravenously daily for 5 days and then, beginning at 28 days, weekly for 48 weeks). MEASUREMENTS: Rates of cancer recurrence and death. Early- and late-treatment side effects. RESULTS: With all 929 eligible patients able to be followed for 5 years or more (median follow-up, 6.5 years), fluorouracil plus levamisole reduced the recurrence rate by 40% (P < 0.0001) and the death rate by 33% (P = 0.0007). Levamisole reduced the recurrence rate by only 2% and the death rate by only 6%. With few exceptions, toxicity was mild and patient compliance was excellent. No evidence of late side effects was seen. CONCLUSION: Fluorouracil plus levamisole is tolerable adjuvant therapy to surgery; it has been confirmed to substantially increase cure rates for patients with high-risk (stage III) colon cancer. It should be considered standard treatment for all such patients not entered into clinical trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Fornix-based versus limbal-based conjunctival flaps in initial trabeculectomy with postoperative 5-fluorouracil: four-year follow-up findings.

PURPOSE: To evaluate the safety and efficacy of fornix-based conjunctival flap versus limbal-based flap in initial trabeculectomy with postoperative 5-fluorouracil. METHODS: 29 patients (58 eyes) with bilateral primary open-angle glaucoma (POAG) were included in the study. Patients were randomly assigned to have a fornix-based conjunctival flap in one eye and a limbal-based flap in the other, followed by subconjunctival injection of 5-fluorouracil. RESULTS: Mean intraocular pressure (IOP) 2 years after treatment was 12.9 +/- 12.25 mmHg in eyes with fornix-based conjunctival flaps and 13.1 +/- 16.81 mmHg in eyes with limbal-based conjunctival flaps. At 4 years, mean IOP was 14.7 +/- 9.61 mmHg in eyes with fornix-based conjunctival flaps and 15.1 +/- 7.29 mmHg in eyes with limbal-based conjunctival flaps. Cumulative success at 4 years (IOP < 21 mmHg) was 89.6% in eyes with fornix-based conjunctival flaps versus 86.2% in eyes with limbal-based conjunctival flaps with medications. Cystic leaking blebs occurred in two cases, both with limbal-based flaps. CONCLUSION: The efficacy of limbal- and fornix-based conjunctival flaps in initial trabeculectomy with postoperative 5-fluorouracil was not significantly different; however, in this study cystic leaking blebs were encountered only in eyes with limbal-based conjunctival flaps.

Adult↗
PubMedDate not supplied

Cimetidine enhances the antiproliferative effect of 5-fluorouracil on colon carcinoma SW620.

We investigated the effects of cimetidine on p-glycoprotein and on the antiproliferative effect of various anticancer drugs which are recognized by p-glycoprotein. We used colon carcinoma SW620 cells and their doxorubicin resistant SW620 Ad300 derived cells, the latter express p-glycoprotein and have multidrug resistance phenotype. To assess the effect of cimetidine on the efflux activity of p-glycoprotein, we examined its effects on the accumulation of rhodamine123 which is recognized by p-glycoprotein. Cimetidine had no effect on rhodamine123 accumulation on either cell line. Cimetidine did not enhance the antiproliferative effect of any of the anticancer drugs investigated. This indicates that cimetidine was not recognized by p-glycoprotein. However, cimetidine remarkably enhanced the antiproliferation effects of 5-fluorouracil on SW620 cells, not those of 5-fluorouracil on SW620 Ad300, whereas cimetidine itself showed little effect on antiproliferation. This finding indicates that combination therapy using 5-fluorouracil and cimetidine might be useful for cancer patients.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Compatibility study of 5-fluorouracil with PVC bags after repackaging into two types of infusion admixtures.

The stability and compatibility of 5-fluorouracil (5-FU) in admixtures for continuous intravenous infusion using PVC bags and administration sets were studied. 5-fluorouracil was reconstituted and diluted to 1.8 mg/ml for infusion in polyvinyl chloride and glass containers, and to 1 mg/ml to 16 mg/ml for storage in polyvinyl chloride bags containing 5 per cent dextrose or 0.9 per cent sodium chloride injections. Admixtures were stored at +4 degrees C and with protection from light, for 7 days. Analyses were performed by HPLC. No significant drug loss was observed during simulated infusions using PVC infusion bags and administration sets vs glass bottles and administration sets, over an infusion period used in hospitals (24 h). The solution stored at +4 degrees C with protection from light in PVC bags showed that at 1 mg/ml to 16 mg/ml, 5-fluorouracil was stable at least for 7 days in 0.9 per cent sodium chloride and 5 per cent dextrose.

Antimetabolites, Antineoplastic↗
PubMed2000

Metabolites of 2'-fluoro-2'-deoxy-D-glucose detected by 19F magnetic resonance spectroscopy in vivo predict response of murine RIF-1 tumors to 5-fluorouracil.

There is a clinical need for early detection of tumor response to therapy. This study aimed to determine whether metabolites of fluorodeoxyglucose (FDG) detected in solid mouse tumors in situ by I9F magnetic resonance spectroscopy (19F MRS) correlated with response to 5-fluorouracil chemotherapy. After injection of FDG (1.4 mmol/kg i.p.), uptake and metabolism was monitored for 2 h in RIF-1 tumors. FDG was detectable immediately, and after 10 min, a second broad peak was detected 5-6 ppm upfield. 19F MRS analysis of cell and tumor extracts in vitro showed that the upfield peak (> or =15% of the total detectable 19F signal) consisted of the epimer alpha-fluorodeoxymannose (FDM) and various conjugates. Mice treated with 5-fluorouracil (130 mg/kg) received, 48 h later, a repeat dose of FDG. The change in the rate of FDM formation, but not the FDG or total 19F signal, correlated significantly with the response to 5-fluorouracil (P = 0.032), suggesting that 19F MRS of FDM metabolism in vivo may be a novel means of predicting tumor response.

Animals↗
PubMedDate not supplied

Haematological toxicity following different dosing schedules of 5-fluorouracil and epirubicin in rats.

AIM: To study the effects of single and fractionated doses of 5-fluorouracil and epirubicin on the leukocyte counts in rats. METHODS: Six different dosing patterns of each drug were injected within one day. The leukocytes were followed for 11-15 days. Pharmacokinetic models were developed using NONMEM. Quantitative and qualitative pharmacokinetic-pharmacodynamic relationships were investigated. RESULTS: A one-compartment model with non-linear elimination described 5-fluorouracil pharmacokinetics and a three-compartment model described epirubicin concentration data. Sigmoidal or basic Emax-models quantified the relationships between individual AUCs and decreases in leukocytes, for both drugs. Similar relationships between AUC and toxicity were found, regardless of whether the drugs were given as single or fractionated doses. CONCLUSION: Quantitative relationships between AUC and the effect on leukocytes were established for 5-fluorouracil and epirubicin. However, no schedule dependence was indicated for the schedules used in the study.

Animals↗
PubMed2002

[Combined high dose leucovorin and 5-fluorouracil continuous infusion for head-neck and digestive tract cancers].

OBJECTIVE: To evaluate the feasibility of combined high dose leucovorin plus 5-fluorouracil infusion for head-neck and digestive tract cancers. METHODS: Fifty-six patients with head-neck and digestive tract cancer were treated by combined high dose leucovorin (HD-CF) plus 5-fluorouracil (5-Fu) 48 hour continuous infusion with each patient receiving an average of 3.8 cycles (2-6 cycles). Twenty-five of these 56 patients were untreated and 31 recurrent. Their clinical stages were II 4, III 13 and IV 39. RESULTS: The over all response rate (CR + PR) was 35.7% and the clinical beneficial response rate was 80.4%. The main side effects were peripheral phlebitis, suppression of bone marrow, oral ulcer, nausea and vomiting of grade I to II. CONCLUSION: High dose leucovorin plus 5-fluorouracil 48 hour continuous infusion is useful with favorable cost/utility ratio for head-neck and digestive tract cancer patients. Further studies are warranted.

Adult↗
PubMed2001

Five-day infusion of fluorouracil and vinorelbine for advanced breast cancer patients treated previously with anthracyclines.

Vinorelbine has proven to be effective in pretreated metastatic breast cancer patients. In particular, no cross-resistance with anthracyclines has been demonstrated. Protracted 5-fluorouracil infusion presents a better pharmacological profile than its bolus administration. The aim of this study was to investigate the efficacy and toxicity of the combination of these two antitumor drugs in patients with metastatic breast cancer who had been previously treated with anthracycline-containing regimens. From February 1998 to January 2000, 65 patients were enrolled into the study The most important inclusion criteria were as follows: Karnofsky 70-100, measurable or evaluable disease and normal renal, hepatic, bone marrow and cardiac function. Mean age was 48 years (range: 31-70). Fourteen of the 65 women had already received more than one chemotherapy line. Twenty-three patients had previously been treated with taxanes. Sites of involvement were the lungs in 50% of the patients, the liver in 37%, soft tissue in 72%, bone in 58% and other sites in 32%. Treatment consisted of vinorelbine 25 mg/m2 administered on days 1 and 6 every 21 days and 5-fluorouracil 700 mg/m2/day for 5 consecutive days. The total number of cycles was 340 (mean: five cycles). The treatment was well tolerated. Febrile neutropenia was observed in 4.6% of patients. Fourteen percent of patients experienced grade 3 or 4 neutropenia, and 3% experienced grade 3 thrombocytopenia. Grade 3 stomatitis was observed in 9.2% of patients, grade 3 neurologic toxicity was observed in 1.5%, and grade 3 cardiotoxicity in 4.6%. Grade 3 site reaction occurred in 3% of patients. Sixty patients were evaluated for response. One patient (1.7%) attained complete clinical response and 28 (46.7%) attained partial response. In 22 patients (36.6%) stable disease was documented and nine patients (15%) progressed while on treatment. Median time to progression was 24 weeks, median duration of response was 35 weeks and median overall survival was 41 weeks. Vinorelbine with 5-day infusion of 5-fluorouracil presented high therapeutic activity in breast cancer patients previously treated with anthracyclines, with acceptable toxicity.

Adult↗
PubMed2002

Randomized trial evaluating a new 0.5% fluorouracil formulation demonstrates efficacy after 1-, 2-, or 4-week treatment in patients with actinic keratosis.

The efficacy and safety of a new 0.5% fluorouracil topical cream were compared with vehicle control for the treatment of actinic keratosis (AK). Active treatment applied once daily for 1, 2, or 4 weeks was more effective than vehicle control in achieving reduction from baseline in lesion counts and lesion clearance. Active treatment also resulted in significantly better global assessments of overall improvement. Treatment was effective regardless of the number of baseline lesions. Although longer treatment duration correlated with greater efficacy, treatment for 1, 2, or 4 weeks was effective. This new microsphere-based fluorouracil formulation was generally well tolerated; adverse events were primarily limited to facial irritation that resolved quickly after treatment. This new treatment provides a safe alternative to the topical fluorouracil formulations currently available for the 1-, 2-, or 4-week treatment of AK.

Administration, Topical↗
PubMed2003

[FTIR studies of chlorobenly-5-fluorouracil porphyrin].

In this paper new kind of porphyrin compounds was prepared, which combined well the affinity of prophyrin to malignant tumour with anticancer of 5-fluorouracil porphyrin. The IR spectra of m- and p-chlorophenyl-5-fluorouracil prophyrin were obtained and analyzed. The IR absorption peaks were investigated and concluded in detail. The IR absorption rule of chloropenly-5-fluorouracil prophyrin which occurred when m-substitution and p-substitution appeared respectively on phenyl, and single substitution of N1 and double substitution of N1 appeared respectively on phenyl or N1 and N1, N3 positions on pyrimidine ring was also discussed. The results show that the relative intensity of nu c-o stretching vibration changed obviously by field-effect when the substitution was strong electro-negative group. Meanwhile, the IR spectral characteristics of the compounds mentioned above were revealed, and this can be used to deduce the stereochemistry structure of them.

Antimetabolites, Antineoplastic↗
PubMed1992

[A case report of metastatic colonic carcinoma in the liver effectively treated by long-term, ambulatory and continuous, intra-hepatic-arterial infusion of 5-fluorouracil using disposable multi-day-type infusor].

A 42-year-old female was diagnosed as having sigmoid colonic carcinoma with multiple metastases in the liver. Following sigmoid colectomy and descending colostomy, a catheter was inserted from the right gastroepiploic artery to the proper hepatic artery. From the day of surgery 5-Fluorouracil was administered in doses of 250 mg/day continuously through a catheter over the 2-month period of hospitalization. After the patient was discharged, 250 mg/day of 5-Fluorouracil was administered at home using Vaxter Infusor according to a regimen of 10-day continuous infusion and subsequent 4-day rest. Five months after the initial operation, the serum CEA level decreased dramatically, and CT scan of the liver revealed the complete disappearance of the metastases. The patient underwent a second operation in which the colostomy was closed, and she is doing well at this writing. This case suggests that long-term, ambulatory, continuous and intra-hepatic-arterial infusion of 5-Fluorouracil can be a very effective treatment not only in reducing the hepatic metastases but also in improving the quality of life of patients with colonic carcinoma.

Adult↗
PubMed2004

[Preparation and properties of 5-fluorouracil-loaded chitosan microspheres for the intranasal administration].

OBJECTIVE: To study the preparation technique and release characteristic of 5-fluorouracil loaded chitosan microspheres for the intranasal administration. METHODS: Using the liquid paraffin as the oil phase,and span-80 as the emuifier; 5-fluorouracil-loaded chitosan microspheres were achieved by emulsion-chemical crosslink technique. The orthogonal experimental design was applied to optimize the preparation procedure. Dynamic dialysis method was used to determine the releasing characteristic of microspheres in vitro and it influencing factors. Swelling behavior was expressed by swelling ratio. The degree of mucoadhesion was investigated by determining the mucociliary transport rate(MTR) of the microparticle across a frog palate. RESULTS: Microspheres with a good shape and narrow size distribution were prepared. The average diameter was (43+/-4) microm. The drug loading was 38.5%+/-1.0%. The entrapment efficiency was 79.0%+/-1.8%. The drug release profile in vitro could be described by Higuichi equation Q=0.1035t(1/2)+0.0284 (r=0.9965). Chitosan had good mucoadhesive property and caused a significant reduction in MTR(P<0.01). CONCLUSION: The optimized preparation technique is stable and has a high entrapment efficiency. So it could be used to prepare 5-fluorouracil-loaded chitosan microspheres for the intranasal administration. Chitosan is a good material for nasal preparation and has prospective development in the pharmaceutical field.

Adhesiveness↗
PubMed1992

Pharmacokinetics and toxicity of continuous infusion (6S)-folinic acid and bolus 5-fluorouracil in patients with advanced cancer.

Twenty-seven patients with advanced cancer were entered in a phase I study of bolus i.v. 5-fluorouracil at a dose of 370 mg/m2/day for 5 days combined with a continuous i.v. infusion of (6S)-folinic acid for 5.5 days, starting 24 h in advance of the first 5-fluorouracil dose. The dose of (6S)-folinic acid was escalated in cohorts of patients from 250 mg/m2/day to a maximum of 1000 mg/m2/day. The pharmacokinetics of (6S)-folinic acid were studied in the 3 patients given 250 mg/m2/day and in 6 patients given 1000 mg/m2/day. The mean steady-state plasma concentrations of (6S)-folinic acid and its principal metabolite (6S)-5-methyltetrahydrofolate at the 250 mg/m2/day dose were 2.7 and 5.1 microM, respectively. Both concentrations were comparable to the concentrations produced when (6S)-folinic acid was administered as half of a (6R,S)-folinic acid mixture (E. M. Newman et al., Cancer Res., 49:5755-5760, 1989). At the 1000 mg/m2/day dose of (6S)-folinic acid, the concentration of (6S)-folinic acid was 15.3 microM, more than the 4-fold increase predicted by linear pharmacokinetics, while the concentration of (6S)-5-methyltetrahydrofolate was only 16.5 microM. The change in the ratio of the parent compound to its metabolite was accounted for by a decrease in the nonrenal clearance of (6S)-folinic acid, probably indicating saturation of its metabolism. The toxicities observed in this phase I trial, including stomatitis, diarrhea, neutropenia, and anemia, did not differ in nature or severity from those produced by 5-fluorouracil and (6R,S)-folinic acid when administered on the same schedule. Finally, the degree of toxicity did not appear to depend on the dose of (6S)-folinic acid over the range of doses tested.

Adult↗