A systematic review of raltitrexed-based first-line chemotherapy in advanced colorectal cancer

Abstract

Raltitrexed is a thymidylate synthase inhibitor belonging to the antimetabolite class of cytotoxic drugs. It is also effective in colorectal cancer (CRC) both as a single agent and in combination with other drugs, in particular in those patients with cardiologic risk factors or previous cardiotoxicity. The efficacy of first-line raltitrexed-based chemotherapy containing oxaliplatin (TOMOX) and irinotecan (TOMIRI) was investigated in this systematic review. Studies that enrolled advanced CRC patients for first-line therapy with TOMOX/TOMIRI combinations were identified using electronic databases (Pubmed, SCOPUS, Web of Science, EMBASE, and the Cochrane Library). A systematic analysis was carried out using Comprehensive Meta Analysis (version 2.2.064) software to calculate the pooled response rate and 95% confidence limits. The median pooled overall survival and progression-free survival were also calculated. Results for TOMOX and TOMIRI studies were compared using the two-sided Student's t-test. We tested for significant heterogeneity using Cochran's χ-test and I index. Twelve studies published between 2001 and 2012 were eligible for this analysis and a total of 735 patients were enrolled in these studies. The overall response rate was 40% (95% confidence interval 34-46%): 43.9% for TOMOX and 34.1% for TOMIRI arms. The weighted median overall survival and progression-free survival times were 14.6 and 6.7 months, respectively. Neutropenia and liver toxicity were more frequent with TOMOX, whereas neutropenia and diarrhea were more frequent with TOMIRI. However, compared with historical FOLFOX and FOLFIRI trials, raltitrexed-based doublets are associated with less neutropenia and gastrointestinal toxicity and uncommon cardiotoxicity. TOMOX and TOMIRI doublets are active as first-line chemotherapy for advanced CRC and seem useful in particular when the use of 5-fluorouracil is contraindicated for cardiac comorbidity.

Raltitrexed based Transcatheter Arterial Chemoembolization (TACE) for Unresectable Hepatocellular Carcinoma: A Single-center Randomized Controlled Study

“…Although the alanine aminotransferase level and bilirubin were increased, these abnormalities resolved within 5 days and did not show any relevant deterioration. The occurrence of main adverse events including biochemistry level changes and gastrointestinal adverse reactions in our study were consistent with that reported previously [20]. However, Sahara et al reported that Grade 3 transaminase elevation and hepatic artery abnormality in TACE with multiple anti-cancer drugs (epirubicin, cisplatin, mitomycin C, and 5-fluorouracil) was significantly greater than that in the epirubicin group among 63 consecutive patients who underwent TACE prospectively [7].…”

Raltitrexed plus oxaliplatin-based transarterial chemoembolization in patients with unresectable hepatocellular carcinoma

“…Raltitrexed is a direct thymidylate synthase inhibitor belonging to the antimetabolite class of cytotoxic drugs [8]. It is has been reported to be effective in a number of tumor types both as a single agent or in combination with other drugs such as DOX and OXA [7]. Raltitrexed has been shown to have no cardiac toxicity and can potentially serve as a substitute for conventional drugs such as 5-FU [5,17].…”

“…The first-line drugs used in TACE include fluorouracil (5-FU), doxorubicin (DOX), and oxaliplatin (OXA), and are associated with a number of adverse effects, indicating a need for an alternative agent [5]. Raltitrexed (also known as tomudex) is a quinazoline antifolate thymidylate synthase inhibitor [6] that has been shown to have anticancer effects in both preclinical and clinical studies [7][8][9][10]. Reports have shown its efficacy and safety in many tumor types including colorectal and breast cancers; however, the clinical data of raltitrexed in HCC treatment are rare.…”

Optimizing Adjuvant Therapy and Survivorship Care of Stage III Colon Cancer

“…Raltitrexed is a direct thymidylate synthase inhibitor which has been compared with 5-FU in the metastatic setting and appears to be noninferior [51]. When raltitrexed is combined with oxaliplatin (TOMOX) in the metastatic setting, it appears to have similar efficacy to FOLFOX in both first and second line settings, but this has not been validated in the context of a large Phase III trial [52].…”