Is Levoleucovorin an Alternative to Racemic Leucovorin? A Literature Review

Kovoor, Philip; Karim, Syed Mustafa; Marshall, John L.

doi:10.3816/ccc.2009.n.034

Cited by 17 publications

(6 citation statements)

References 17 publications

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“…This indicates that substituting arfolitixorin for leucovorin may improve outcomes in these pretreated patients, and justifies the current study in which the enrolled population exclusively comprised patients with untreated advanced colorectal cancer. The choice of racemic leucovorin instead of levoleucovorin is justified on the basis of evidence indicating that levoleucovorin, compared with racemic leucovorin, does not improve efficacy or safety in gastrointestinal cancers ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial

Tabernero,

Yoshino,

Stintzing

et al. 2024

Cancer Research Communications

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PURPOSE: Suboptimal treatment outcomes with 5-FU/folate, the standard of care for metastatic colorectal cancer (mCRC), have generated interest in optimizing the folate. Arfolitixorin ([6R]-5,10-methylene-tetrahydrofolate) is an immediately active folate and may improve outcomes over the existing standard of care (leucovorin). EXPERIMENTAL DESIGN: AGENT was a randomized, phase III study (NCT03750786). Patients with mCRC were randomized to arfolitixorin (120 mg/m2 given as two IV bolus doses of 60 mg/m2) or leucovorin (400 mg/m2 given as a single IV infusion) plus 5-FU, oxaliplatin, and bevacizumab. Assessments were performed every 8 weeks. The primary endpoint was the superiority of arfolitixorin for overall response rate (ORR). RESULTS: Between February 2019 and April 2021, 490 patients were randomized (245 to each arm). After a median follow-up of 266 days, the primary endpoint of superiority for ORR was not achieved (48.2% for arfolitixorin versus 49.4% for leucovorin, P for superiority = 0.57). Outcomes were not achieved for median PFS (12.8 and 11.6 months, P = 0.38), median DoR (12.2 and 12.9 months, P = 0.40) and median OS (23.8 and 28.0 months, P = 0.78). The proportion of patients with an AE of grade ≥3 severity was similar between arms (68.7% and 67.2%, respectively), as was quality of life. BRAF mutations and MTHFD2 expression were both associated with a lower PFS with arfolitixorin. CONCLUSIONS: The study failed to demonstrate clinical benefit of arfolitixorin (120 mg/m2) over leucovorin. However, it provides some useful insights from the first-line treatment setting, including the effect of gene expression on outcomes.

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Section: Discussionmentioning

confidence: 99%

A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial

Tabernero,

Yoshino,

Stintzing

et al. 2024

Cancer Research Communications

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“…Second-line chemotherapy has been shown to improve the prognosis of patients with UR PC [ 12 , 19 – 23 ]. In a randomized global phase III trial, nal-IRI plus 5-FU/LV demonstrated superiority over 5-FU/LV as second-line chemotherapy for patients with metastatic PC.…”

Section: Discussionmentioning

confidence: 99%

Parallel administration of nanoliposomal irinotecan and levo-leucovorin for pancreatic cancer

Takada,

Ikezawa,

Yamai

et al. 2023

BMC Cancer

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Background Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU)/levo-leucovorin (Levo-LV) was approved for unresectable pancreatic cancer (UR-PC) in March 2020 in Japan. Levo-LV is administered by intravenous infusion over 120 min following 90 min intravenous infusion of nal-IRI (conventional method), causing a significant burden on both patients and the outpatient chemotherapy room owing to the prolonged administration time. Thus, from July 2021, we introduced the simultaneous intravenous administration of nal-IRI and Levo-LV (parallel method) with the approval of the institutional regimen committee. Methods We retrospectively reviewed the data of 69 patients with UR-PC who received nal-IRI plus 5-FU/Levo-LV at our hospital between June 2020 and October 2021. We examined the safety of the parallel method and compared the treatment outcomes and administration times between the two methods. Results The median age was 66 years (54%, male). Disease statuses were locally advanced, metastatic, and postoperative recurrence after pancreatectomy in 7, 50, and 12 patients, respectively. Nal-IRI plus 5-FU/Levo-LV treatment was second and third-line or later in 35 and 34 patients, respectively. No intravenous line problems were observed during the parallel administration of nal-IRI and Levo-LV. Although there were no significant differences in response rates and adverse events between the two methods, the administration time was significantly shorter in the parallel method than in the conventional method. Conclusion The parallel administration of nal-IRI and Levo-LV is clinically safe and not inferior in efficacy. Moreover, parallel administration may offer convenience to patients and healthcare workers by reducing administration time.

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“…Folinic acid is composed of 2 corresponding isomers in the same proportion, of which levofolinate was a eutomer 8 . l ‐formyltetrahydrofolate is the active ingredient of levofolinate, which can metabolize to l ‐5‐methyltetrahydrofolate.…”

Section: Figurementioning

confidence: 99%

Three‐Period Bioequivalence Study of Sodium Levofolinate Injection With Calcium Levofolinate for Injection and Sodium Folinate for Injection in Healthy Chinese Subjects

Qiu

Liu

Wang

et al. 2023

Clinical Pharm in Drug Dev

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The aim of this study was to compare the bioequivalence and safety of test preparation sodium levofolinate injection with reference preparations of calcium levofolinate for injection and sodium folinate for injection in China. A singlecenter, randomized, open-label, 3-period, crossover test was conducted on 24 healthy subjects. Plasma concentration of levofolinate, dextrofolinate, and their metabolites L-5-methyltetrahydrofolate and D-5-methyltetrahydrofolate were quantified by a validated chiral-liquid chromatography-tandem mass spectrometry method. All adverse events (AEs) were documented to evaluate safety as they occurred and evaluated descriptively. Pharmacokinetic parameters (maximum plasma concentration, time to maximum concentration, area under the plasma concentration-time curve over the dosing interval, area under the plasma concentration-time curve from time 0 to infinity, terminal elimination half-life, and terminal rate constant) of 3 preparations were calculated. A total of 8 subjects (10 cases) of AEs occurred in this trial. No serious AEs or unexpected serious adverse reactions were observed. Sodium levofolinate was bioequivalent to calcium levofolinate and sodium folinate in Chinese subjects, and the 3 preparations were all well tolerated.

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Is Levoleucovorin an Alternative to Racemic Leucovorin? A Literature Review

Cited by 17 publications

References 17 publications

A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial

A Randomized Phase III Study of Arfolitixorin versus Leucovorin with 5-Fluorouracil, Oxaliplatin, and Bevacizumab for First-Line Treatment of Metastatic Colorectal Cancer: The AGENT Trial

Parallel administration of nanoliposomal irinotecan and levo-leucovorin for pancreatic cancer

Three‐Period Bioequivalence Study of Sodium Levofolinate Injection With Calcium Levofolinate for Injection and Sodium Folinate for Injection in Healthy Chinese Subjects

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