Mature results from three large controlled studies with raltitrexed ('Tomudex')

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Raltitrexed is a novel quinazoline folate analogue and a specific inhibitor of thymidylate synthase.
• Extensive phase II and III clinical studies have evaluated raltitrexed's efficacy and tolerability.

Purpose of the Study:

• To compare the clinical efficacy and tolerability of raltitrexed with 5-fluorouracil (5-FU) plus leucovorin (LV) in advanced colorectal cancer.
• To assess response rates, palliative improvements, survival, and toxicity profiles of raltitrexed versus 5-FU/LV regimens.

Main Methods:

• Phase III international trials (Studies 3 and 12) compared raltitrexed (3 mg m⁻²) with 5-FU/LV (Mayo or Machover regimens).
• A North American study (Study 10) compared raltitrexed doses (3.0 and 4.0 mg m⁻²) against 5-FU/LV, with the higher raltitrexed dose discontinued due to toxicity.
• Follow-up periods ranged from 9 to 26 months for survival data.

Main Results:

• Objective response rates and palliative improvements were similar between raltitrexed and 5-FU/LV.
• Survival outcomes were statistically similar in Studies 3 and 12; Study 10 showed inferior survival with raltitrexed, potentially due to early toxicity and altered treatment administration.
• Raltitrexed demonstrated significantly lower rates of mucositis compared to 5-FU-based therapy, with predictable toxicity and similar monthly costs.

Conclusions:

• Raltitrexed is an effective alternative to 5-FU-based therapy for advanced colorectal cancer.
• Raltitrexed offers an acceptable and predictable toxicity profile, notably minimizing mucositis.
• The convenient administration schedule of raltitrexed is advantageous for patients and healthcare providers.