A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143)

Vieitez, José María; Valladares, Manuel; Peláez, Ignacio; González, Luis de Sande; Garcı́a-Foncillas, Jesús; García-López, José Luis; García-Girón, Carlos; Reboredo, Margarita; Bovio, H.; Lacave, Ángel J.

doi:10.1007/s10637-010-9400-z

Cited by 11 publications

(10 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1), nine phase III trials and 11 randomized phase II trials (Table 1) [11-30]. A total of 7,571 patients were enrolled in these trials, and the median number of enrolled patients was 197 (range, 75 to 1,226).…”

Section: Resultsmentioning

confidence: 99%

“…A total of 7,571 patients were enrolled in these trials, and the median number of enrolled patients was 197 (range, 75 to 1,226). The primary endpoint was PFS in 12 trials (60%) [11-15,18,19, 21-24,30], OS in six trials (30%) [16,20,26-29] and ORR in one trial (5%) [17]. In one trial (5%), PFS and OS were co-primary endpoints [25].…”

Section: Resultsmentioning

confidence: 99%

“…Median progression free survival (PFS) and post-progression survival (PPS) in all comparisons with available information (n=24) [11-25],27-30.…”

Section: Figmentioning

confidence: 99%

See 2 more Smart Citations

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis

et al. 2017

View full text Add to dashboard Cite

PurposeThe purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC).Materials and MethodsA systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson’s correlation coefficient (R) and the coefficient of determination (R2).ResultsTwenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, –2.4 to 3.4) for the median PFS and 0.7 months (range, –5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R2=0.539, p < 0.001) and poor correlation (R=0.169, R2=0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident.ConclusionTargeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis

et al. 2017

View full text Add to dashboard Cite

show abstract

“…According to the results of two phase III RCTs (TALENT and TRIBUTE trials), erlotinib was not appropriate for use as a first line treatment for NSCLC [35]. Compared to NSCLC, TKIs' efficacy against CRC and HNSCC was even lower [27,28,[36][37][38]. The most important reason is that some primary EGFR mutations that can enhance the sensitivity to TKIs, such as exon 19 deletion and point mutation L858R in exon 21, are rare in CRC and HNSCC, but relatively common in NSCLC [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Anti-epidermal growth factor receptor therapy for advanced head and neck squamous cell carcinoma: a meta-analysis

Zhang

Chen

Jiang

et al. 2012

Eur J Clin Pharmacol

View full text Add to dashboard Cite

show abstract

“…A trial involving combination of raltitrexed and gefitinib in one arm and raltitrexed alone has been tested on 76 patients as a second-line chemotherapy in advanced mCRC. This combination was well tolerated, but there was no difference in PFS between the arms [33]. The combination of FOLFOX-4 and gefitinib (IFOX) has been tested on previously untreated patients with mCRC.…”

Section: Novel Drugs In Phase 2 Clinical Developmentmentioning

confidence: 99%

Novel Drugs Targeting the Epidermal Growth Factor Receptor and Its Downstream Pathways in the Treatment of Colorectal Cancer: A Systematic Review

Merla

Goel

2012

Chemotherapy Research and Practice

View full text Add to dashboard Cite

Colorectal cancer is the second most common malignancy among men and women in the United States, and the 5-year survival rate remains poor despite recent advances in chemotherapy and targeted agents. The mainstay of therapy for advanced disease remains the cytotoxic chemotherapy including 5-FU, irinotecan, and oxaliplatin. The USFDA approval and introduction of targeted therapies, including cetuximab and panitumumab (monoclonal antibodies targeting the epidermal growth factor receptor (EGFR)) and bevacizumab (monoclonal antibody targeting the vascular epithelial growth factor (VEGF)), has improved the median survival of patients with metastatic colorectal cancer to around 24 months. Clearly, better and more efficacious drugs are needed, and target-specific agents remain the future of cancer treatment. On this front, rapid advances are being made, which are likely to change the future of the management of metastatic colorectal cancer. However, absence of specific biomarkers for the use of targeted agents, in the subset of population who will benefit from the treatment, remains a major drawback. In this paper, we review agents that are in phases 1 and 2 clinical development, specifically targeting the EGFR and its subsequent downstream pathways.

show abstract

A randomized phase II study of raltitrexed and gefitinib versus raltitrexed alone as second line chemotherapy in patients with colorectal cancer. (1839IL/0143)

Abstract: The combination of raltitrexed and gefitinib was well tolerated although was not associated with improved progression free survival in patients with refractory CRC.

Cited by 11 publications

References 31 publications

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis

Anti-epidermal growth factor receptor therapy for advanced head and neck squamous cell carcinoma: a meta-analysis

Novel Drugs Targeting the Epidermal Growth Factor Receptor and Its Downstream Pathways in the Treatment of Colorectal Cancer: A Systematic Review

Contact Info

Product

Resources

About