Randomized Multicenter Phase II Study Comparing a Combination of Fluorouracil and Folinic Acid and Alternating Irinotecan and Oxaliplatin With Oxaliplatin and Irinotecan in Fluorouracil-Pretreated Metastatic Colorectal Cancer Patients

Bécouarn, Y.; Gamelin, Érick; Coudert, Bruno; Négrier, S.; Pierga, Jean‐Yves; Raoul, Jean‐Luc; Provençal, J.; Rixe, Olivier; Krisch, Claude; Germa, Caroline; Békradda, Mohamed; Mignard, D.; Mousseau, M

doi:10.1200/jco.2001.19.22.4195

Cited by 59 publications

(30 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phase I three-drug clinical trials [19,20,21] have already demonstrated nonoverlapping dose-limiting toxicities and safety profiles. Phase II studies [16,17,18, 22, 23] which investigated different three-drug regimens reported interesting data on activity (response rate ranged from 32 to 69.2%, time to tumor progression from 8.2 to 14 months). Falcone et al [22] achieved noteworthy results, with response rate 71.4%, median time to tumor progression 10.4 months and median overall survival 26.5 months.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

An Alternating Regimen of Irinotecan/ 5-Fluorouracil/Folinic Acid and Oxaliplatin/ 5-Fluorouracil/Folinic Acid in Metastatic Colorectal Cancer: A Phase II Trial

Ferrari

Valcamonico²,

Amoroso³

et al. 2005

Oncology

View full text Add to dashboard Cite

Objective: To assess the feasibility and activity of a combination schedule with irinotecan (CPT-11), oxaliplatin (L-OHP), brief infusional fluorouracil (5-FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer (MCC) patients. Methods: Fifty consecutive patients were treated with CPT-11 125 mg/m² as a 90-min intravenous infusion, followed by FA 20 mg/m² as an intravenous bolus, and 5-FU 500 mg/m² over a 2-hour intravenous infusion on days 1 and 8. L-OHP was administered at 85 mg/m² over 2 h on day 15, in combination with a FA 60 mg/m² intravenous bolus and 5-FU 600 mg/m² as a 2-hour intravenous infusion on days 15–16. The treatment was repeated every 4 weeks for a maximum of 9 cycles. Results: Twenty-five of 50 assessable patients achieved a complete (n = 5) or partial (n = 20) response, leading to a response rate of 50% (95% CI 35–64%). Eighteen (36%) patients showed stable disease. The median time to tumor progression was 10.3 months (95% CI 9.6–10.9 months). After a median follow-up of 16.4 months, the median survival was not reached. Grade 3 neutropenia (8%), grade 3 nausea/vomiting (6%) and grade 3 diarrhea (2%) were the major adverse events. Conclusion: This alternating three-drug regimen is very well tolerated, manageable and effective in terms of activity and time to progression.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In clinical settings, phase I and II studies have already shown the feasibility and activity of the three-drug combination in both chemo-naïve and pretreated MCC patients [16,17,18,19,20,21,22,23, 27]. …”

Section: Introductionmentioning

confidence: 99%

An Alternating Regimen of Irinotecan/ 5-Fluorouracil/Folinic Acid and Oxaliplatin/ 5-Fluorouracil/Folinic Acid in Metastatic Colorectal Cancer: A Phase II Trial

Ferrari

Valcamonico²,

Amoroso³

et al. 2005

Oncology

View full text Add to dashboard Cite

show abstract

“…It seems that even combined with IRI, TAS-102 could not suppress tumor growth, compared with combination chemotherapies with 5-FU plus OX or 5-FU plus IRI. Second-line chemotherapy generally needs a much higher PFS, for example, that of 5-FU plus OX or 5-FU plus IRI was 8.2 months [6]. In our case, TAS-102 alone could shrink the size of 5-FU-resistant liver metastasis to approximately 60%, and its PFS reached to over 12.5 months without severe toxicities.…”

Section: Discussionmentioning

confidence: 67%

Possibility of TAS-102 as an Early Line Therapy Against Advanced Colorectal Cancer

Yoshida¹,

Fukuda²,

Taguchi³

2016

Oncology and cancer case reports

View full text Add to dashboard Cite

IntroductionColorectal cancer (CRC) is the third most common malignancy in men (746,000 cases, 10.0% of the total) and the second most common in women (614,000 cases, 9.2% of the total) worldwide [1]. The estimated mortality rates in both genders range from 20.3 per 100,000 men and 11.7 per 100,000 women in Central and Eastern Europe to 3.5 and 3.0, respectively, in Western Africa [1]. Almost a quarter of a century ago, metastatic CRC was treated using a single agent, 5-fluorouracil (5-FU), with a median survival time (MST) of approximately 1 year. Thereafter, relevant improvements in not only MST but also progression-free survival (PFS) and response rates have been achieved. The most recently reported MST has exceeded 30 months [2]. Almost a dozen agents, including 5-FU; its derivatives; Irinotecan (IRI); Oxaliplatin (OX); angiogenesis inhibitors, such as bevacizumab, ramucirumab, and aflibercept; anti-epidermal growth factor receptor antibodies, such as cetuximab and panitumumab; and multiple tyrosine kinase inhibitor regorafenib have contributed to this improvement. TAS-102, a new oral anti-cancer agent composed of a 1:0.5 mixture on a molar ratio of α, α, α-trifluorothymidine (TFD) and a thymidine phosphorylase inhibitor (TPI), tipiracil hydrochloride, has demonstrated improved results in MST and PFS, compared with a placebo, in a global phase 3 trial for metastatic CRC refractory to standard therapies [3]. A much safer profile of TAS-102 has also been confirmed, with grade 3/4 neutropenia in 38% and febrile neutropenia in 4% patients. However, the response rate of TAS-102 was lower at 1.6%. This might be due to its usage late in the line. Recently, we have observed a good response of TAS-102 for metastatic CRC as an early line of therapy. Case PresentationA 68-year-old female with rectal cancer underwent abdominoperineal resection at another hospital in January 2014. It was diagnosed as stage 1, according to the TMN classification, and was histopathologically identified as an adenocarcinoma with mutant RAS (the mutation replaces the amino acid glycine with valine at position Abstract Introduction: New drugs have improved the outcome of metastatic colorectal cancer treatment. In Japan, more than 10 agents with at least seven different mechanisms such as 5-fluorouracil (5-FU), irinotecan (IRI), oxaliplatin, angiogenesis inhibitors, anti-epidermal growth factor receptor antibodies, regrafenib, and TAS-102, have been approved. With the increase in the number of alternatives, the importance of choosing the agents increases. To suppress the toxicities of agents is also necessary. To increase the quality of life of the patients should be taken into consideration for their longer survival. TAS-102 has proved to be an effective and safe agent for the 3rd or 4th lines of advanced colorectal cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

“…Inter-individual differences in the pharmacokinetics of its active metabolite, SN-38, cause the variations in the effect of the drug (6). Several studies in relation with different doses and schedules of CPT-11 alone or in combination with other agents are ongoing to investigate its use as first or secondline therapy (7,8), with a view to optimising the therapeutic outcome for these patients.On the other hand, Glutathione S-transferases (GSTs) are considered an important family of detoxifying enzymes for mutagens. They protect cellular macromolecules from damage by catalysing the conjugation of toxic and carcinogenic electrophilic molecules with glutathione.…”

mentioning

confidence: 99%

Potential application of GSTT1-null genotype in predicting toxicity associated to 5-fluouracil irinotecan and leucovorin regimen in advanced stage colorectal cancer patients

Romero¹,

Morales²,

Garcia³

et al. 2006

Oncol Rep

View full text Add to dashboard Cite

Abstract.Our aim was to evaluate the role of C-69T in GSTA1, Ile105Val in GSTP1, null allele in GSTT1 and GSTM1 in the prediction of toxicity in patients treated with 5-Fu/CPT-11/Lv regimens in metastatic CRC patients. Fiftyone patients with CRC metastatic disease were analysed. All patients had bidimensionally measurable disease according to WHO criteria. The gender distribution was 37 (74%) males and 13 (26%) females; age ranged from 41 to 71 years; performance status was in all patients ≥80 (Karnofsky index). The analysis of gene polymorphism was performed in lymphocytes by using PCR-RFLP (GSTA1, GSTP1), PCR (GSTT1, GSTM1) and sequencing analysis (UGT1A1 * 28). An appreciable significant association was observed between the GSTT1-null and toxicity: 57% developed gastrointestinal toxicity grade III versus 23% of patients with GSTT1-present genotype (p=0.053). The other polymorphisms analysed did not show any significant relation with toxicity. Our data suggest that GSTT1-null is associated with a greater probability of developing toxicity to 5-Fu/CPT-11/Lv treatments, indicating a potential application of this genetic analysis in predicting adverse effects of this regimen.Introduction 5-Fluouracil (5-FU) has been the mainstay of treatment for patients with advanced colorectal cancer (CRC) for more than five decades. Irinotecan (CPT-11) has been found to demonstrate at least equivalent efficacy to 5-FU in first-line therapy, favorable quality-of-life assessments and prolonged median survival (1,2). In Europe as well as in the USA, the combination of 5-FU plus CPT-11 is currently recommended as first-line therapy for metastatic CRC treatment (3,4). Risk factors with predictive value for toxicity have been identified in several studies. In this sense, age, performance status, bilirubinaemia, the genetic polymorphism of UDP-glucuronyltransferase-1A1 (UGT1A1) and the drug administration schedule have been show to be related with CPT-11 toxicity (5). Inter-individual differences in the pharmacokinetics of its active metabolite, SN-38, cause the variations in the effect of the drug (6). Several studies in relation with different doses and schedules of CPT-11 alone or in combination with other agents are ongoing to investigate its use as first or secondline therapy (7,8), with a view to optimising the therapeutic outcome for these patients.On the other hand, Glutathione S-transferases (GSTs) are considered an important family of detoxifying enzymes for mutagens. They protect cellular macromolecules from damage by catalysing the conjugation of toxic and carcinogenic electrophilic molecules with glutathione. The resulting complex is less toxic and more readily excreted.The implication of GSTs in the detoxification of heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) and other carcinogens has been related to GST gene alterations with colorectal cancer risk (9,10). Diverse common single nucleotide polymorphisms (SNPs) have been reported for GSTT1, GSTM1, GSTA1 and GSTP1 genes that either abolish, incr...

show abstract

Randomized Multicenter Phase II Study Comparing a Combination of Fluorouracil and Folinic Acid and Alternating Irinotecan and Oxaliplatin With Oxaliplatin and Irinotecan in Fluorouracil-Pretreated Metastatic Colorectal Cancer Patients

Abstract: The every-3-weeks OC combination is safe and active in advanced 5-FU-resistant CRC patients. The lower activity data seen with the tritherapy regimen may be related to the lower dose intensities of irinotecan and oxaliplatin in this schedule.

Cited by 59 publications

References 29 publications

An Alternating Regimen of Irinotecan/ 5-Fluorouracil/Folinic Acid and Oxaliplatin/ 5-Fluorouracil/Folinic Acid in Metastatic Colorectal Cancer: A Phase II Trial

An Alternating Regimen of Irinotecan/ 5-Fluorouracil/Folinic Acid and Oxaliplatin/ 5-Fluorouracil/Folinic Acid in Metastatic Colorectal Cancer: A Phase II Trial

Possibility of TAS-102 as an Early Line Therapy Against Advanced Colorectal Cancer

Potential application of GSTT1-null genotype in predicting toxicity associated to 5-fluouracil irinotecan and leucovorin regimen in advanced stage colorectal cancer patients

Contact Info

Product

Resources

About