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Raltitrexed-induced hepatotoxicity: multivariate analysis of predictive factors
Cristian Massacesi1, Daniele Santini, Marco B L Rocchi
1Medical Oncology, Oncology and Radiotherapy Department of Ancona, Ancona, Italy. c.massacesi@ao-umbertoprimo.marche.it
Anti-Cancer Drugs
|September 10, 2003
Summary
Raltitrexed (TOM) can cause liver toxicity, often seen as elevated transaminase levels. Factors like baseline transaminases, treatment duration, and the TOMOX regimen predict this toxicity, while glutathione and ademethionine show protective effects.
Area of Science:
- Oncology
- Hepatology
- Pharmacology
Background:
- Raltitrexed (Tomudex; TOM) induced hepatotoxicity typically presents as transient transaminase elevations.
- The clinical implications and predictive factors for TOM hepatotoxicity remain unclear, impacting daily practice.
Purpose of the Study:
- To identify predictive factors for Raltitrexed (TOM)-induced hepatotoxicity.
- To evaluate the impact of TOM and TOM plus oxaliplatin (TOMOX) regimens on liver function.
Main Methods:
- Multinomial logistic regression analysis was performed on 584 chemotherapy courses from 130 patients treated with TOM or TOMOX.
- Clinical factors including patient demographics, disease characteristics, and treatment parameters were assessed.
- Creatinine clearance was calculated using the Cockcroft formula before each course.
Main Results:
- Elevated baseline transaminases, increased number of cycles, higher TOM cumulative dose, shorter intervals between courses, and the TOMOX regimen were predictive of hepatotoxicity.
- Glutathione (GSH) and ademethionine (SAMe) demonstrated significant hepatoprotective effects.
- Hepatotoxicity led to treatment delays in 10% of cycles and discontinuation in 6% of patients.
Conclusions:
- Raltitrexed-based hepatotoxicity is a clinically significant side effect, often underestimated, affecting treatment continuity.
- Predictive factors and identified hepatoprotective agents (GSH, SAMe) can aid in managing TOM-induced liver toxicity.
- Understanding these factors is crucial for optimizing cancer treatment strategies involving Raltitrexed.