Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Santini D, Massacesi C, D'Angelillo RM, Marcucci F, Campisi C, Vincenzi B, Pilone A, Bianco V, Bonsignori M, Tonini G. Raltitrexed plus weekly oxaliplatin as first-line chemotherapy in metastatic colorectal cancer: a multicenter non-randomized phase ii study. Med Oncol 2004;21:59-66. [PMID: 15034215 DOI: 10.1385/mo:21:1:59] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2003] [Accepted: 12/01/2003] [Indexed: 12/20/2022]

For:	Santini D, Massacesi C, D'Angelillo RM, Marcucci F, Campisi C, Vincenzi B, Pilone A, Bianco V, Bonsignori M, Tonini G. Raltitrexed plus weekly oxaliplatin as first-line chemotherapy in metastatic colorectal cancer: a multicenter non-randomized phase ii study. Med Oncol 2004;21:59-66. [PMID: 15034215 DOI: 10.1385/mo:21:1:59] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2003] [Accepted: 12/01/2003] [Indexed: 12/20/2022]

Number

Cited by Other Article(s)

Pijeira Perez Y, Hughes DA. Evidence Following Conditional NICE Technology Appraisal Recommendations: A Critical Analysis of Methods, Quality and Risk of Bias. PHARMACOECONOMICS 2024;42:1373-1394. [PMID: 39249730 PMCID: PMC11564307 DOI: 10.1007/s40273-024-01418-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/14/2024] [Indexed: 09/10/2024]

Abstract

BACKGROUND

The National Institute for Health and Care Excellence (NICE) may approve health technologies on condition of more evidence generated only in research (OiR) or only with research (OwR). NICE specifies the information needed to comply with its request, although it may not necessarily guarantee good quality and timely evidence for re-appraisal, before reaching a final decision.

AIM

This study aimed to critically appraise the methods, quality and risk of bias of evidence generated in response to NICE OiR and OwR technology appraisal (TA) and highly specialised technologies (HSTs) recommendations.

METHODS

NICE TAs (between March 2000 and September 2020) and HST evaluations (to October 2023) of medicines were reviewed. Conditional recommendations were analysed to identify the evidence requested by NICE for re-appraisal. The new evidence was analysed for compliance with NICE's request and assessed using the Cochrane Collaboration's tools for risk of bias in randomised trials and the ROBINS-I tool for non-randomised evidence.

RESULTS

NICE made 54 conditional recommendations from TAs (13 OiR and 41 OwR) and five conditional recommendations for HSTs (all OwR). Of these, 16 TAs presented additional evidence for re-appraisal (9 OiR [69%] and 7 OwR [17%]) and three HSTs (3 OwR [60%]). Two of the nine re-appraised TAs with OiR recommendation and four of the seven OwR complied fully with NICE's request for further evidence, while all three from the HSTs complied. The majority of re-appraised TAs and HSTs included evidence that was deemed to be at serious, high, moderate or unclear risk of bias. Among the 26 randomised controlled trials from TAs assessed, eight were categorised as having low risk of bias in all domains and ten had at least one domain as a high risk of bias. Reporting was unclear for the remainder. Twenty-two non-randomised studies, primarily single-arm studies, were susceptible to biases mostly due to the selection of participants and to confounding. Two HSTs provided evidence from randomised controlled trials which were classified as unclear or high risk of bias. All non-randomised evidence from HSTs were categorised as moderate or serious risk of bias.

CONCLUSIONS

There is widespread non-compliance with agreed data requests and important variation in the quality of evidence submitted in response to NICE conditional approval recommendations. Quality standards ought to be stipulated in respect to evidence contributing to re-appraisals following NICE conditional approval recommendations.

Collapse

Cheng Y, Teng Z, Zhang Y, Jin B, Zheng Z, Man L, Wang Z, Teng Y, Yu P, Shi J, Luo Y, Wang Y, Zhang J, Zhang H, Liu J, Chen H, Xiao J, Zhao L, Zhang L, Jiang Y, Chen Y, Zhang J, Wang C, Liu S, Qu J, Qu X, Liu Y. Irinotecan plus raltitrexed as second-line treatment in locally advanced or metastatic colorectal cancer patients: a prospective open-label, single-arm, multi-center, phase II study. BMC Cancer 2024;24:1082. [PMID: 39223545 PMCID: PMC11368032 DOI: 10.1186/s12885-024-12831-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024] Open

Abstract

BACKGROUND

Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size.

METHODS

This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m2, d1) and irinotecan (180 mg/m2, d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety.

RESULTS

A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths.

CONCLUSIONS

The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients).

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017.

Collapse

Affiliation(s)

Yu Cheng Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Zan Teng Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Yanqiao Zhang Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China
Bo Jin Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Zhendong Zheng Department of Oncology, Northern Theater Command General Hospital, Shenyang, Liaoning Province, China
Li Man Department of Oncology, Anshan Cancer Hospital, Anshan, Liaoning Province, China
Zhenghua Wang Department of Oncology, The First Affiliated Hospital Of Jinzhou Medical University, Jinzhou, Liaoning Province, China
Yuee Teng Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Ping Yu Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Jing Shi Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Ying Luo Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Ying Wang Department of Oncology, Shengjing Hospital Of China Medical University, Shenyang, Liaoning Province, China
Jingdong Zhang Department of Oncology, Liaoning Cancer Hospital, Shenyang, Liaoning Province, China
Huijuan Zhang Department of Oncology, Tieling Central Hospital, Tieling, Liaoning Province, China
Jiwei Liu Department of Oncology, The First Affiliated Hospital Of Dalian Medical University, Dalian, Liaoning Province, China
Hao Chen Department of Oncology, Liaoyang Liaohua Hospital, Liaoyang, Liaoning Province, China
Jiawen Xiao Department of Oncology, Shenyang Fifth People Hospital, Shenyang, Liaoning Province, China
Lei Zhao Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Lingyun Zhang Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Yu Jiang Department of Oncology, Panjin Central Hospital, Panjin, Liaoning Province, China
Ying Chen Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China
Jian Zhang Department of Oncology, Liaoyang City Central Hospital, Liaoyang, Liaoning Province, China
Chang Wang Department of Oncology, The First Hospital Of Jilin University, Changchun, Jilin Province, China
Sa Liu Department of Oncology, The Fourth Affiliated Hospital Of China Medical University, Shenyang, Liaoning Province, China
Jinglei Qu Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China. Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China.
Xiujuan Qu Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China. Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China.
Yunpeng Liu Department of Oncology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China. Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, Liaoning Province, China. Liaoning Province Clinical Research Center for Cancer, Shenyang, Liaoning Province, China. Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Ministry of Education, Shenyang, Liaoning Province, China.

Collapse

Transarterial chemoembolization with raltitrexed-based or floxuridine-based chemotherapy for unresectable colorectal cancer liver metastasis. Clin Transl Oncol 2018;21:443-450. [PMID: 30306400 DOI: 10.1007/s12094-018-1942-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 09/02/2018] [Indexed: 12/22/2022]

A systematic review of raltitrexed-based first-line chemotherapy in advanced colorectal cancer. Anticancer Drugs 2016;25:1122-8. [PMID: 24869761 DOI: 10.1097/cad.0000000000000133] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

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.

Collapse

Han J, Zhao J, Xu J, Wen Y. Mesenchymal stem cells genetically modified by lentivirus-mediated interleukin-12 inhibit malignant ascites in mice. Exp Ther Med 2014;8:1330-1334. [PMID: 25187849 PMCID: PMC4151654 DOI: 10.3892/etm.2014.1918] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Accepted: 07/08/2014] [Indexed: 02/05/2023] Open

TS mRNA levels can predict pemetrexed and raltitrexed sensitivity in colorectal cancer. Cancer Chemother Pharmacol 2013;73:325-33. [PMID: 24281197 DOI: 10.1007/s00280-013-2354-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 11/07/2013] [Indexed: 01/01/2023]

Gravalos C, Salut A, García-Girón C, García-Carbonero R, León AI, Sevilla I, Maurel J, Esteban B, García-Rico E, Murias A, Cortés-Funes H. A randomized phase II study to compare oxaliplatin plus 5-fluorouracil and leucovorin (FOLFOX4) versus oxaliplatin plus raltitrexed (TOMOX) as first-line chemotherapy for advanced colorectal cancer. Clin Transl Oncol 2012;14:606-12. [PMID: 22855138 PMCID: PMC3427491 DOI: 10.1007/s12094-012-0843-x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2011] [Accepted: 11/14/2011] [Indexed: 12/27/2022]

Thymidylate synthase inhibitors. ACTA ACUST UNITED AC 2006. [DOI: 10.1016/j.uct.2006.09.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]

Cao S, Bhattacharya A, Durrani FA, Fakih M. Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer. Expert Opin Pharmacother 2006;7:687-703. [PMID: 16556086 DOI: 10.1517/14656566.7.6.687] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]

Walling J. From methotrexate to pemetrexed and beyond. A review of the pharmacodynamic and clinical properties of antifolates. Invest New Drugs 2006;24:37-77. [PMID: 16380836 DOI: 10.1007/s10637-005-4541-1] [Citation(s) in RCA: 120] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]

Khamly K, Jefford M, Michael M, Zalcberg J. Beyond 5-fluorouracil: new horizons in systemic therapy for advanced colorectal cancer. Expert Opin Investig Drugs 2006;14:607-28. [PMID: 16004591 DOI: 10.1517/13543784.14.6.607] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]

Massacesi C, Terrazzino S, Marcucci F, Rocchi MB, Lippe P, Bisonni R, Lombardo M, Pilone A, Mattioli R, Leon A. Uridine diphosphate glucuronosyl transferase 1A1 promoter polymorphism predicts the risk of gastrointestinal toxicity and fatigue induced by irinotecan-based chemotherapy. Cancer 2006;106:1007-16. [PMID: 16456808 DOI: 10.1002/cncr.21722] [Citation(s) in RCA: 97] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]

Abstract

BACKGROUND

In the current Phase II study, the authors evaluated the association between genomic polymorphic variants in uridine diphosphate glucuronosyl transferase (UGT1A1), methylenetetrahydrofolate reductase (MTHFR), and thymidylate synthase (TS) genes, and the incidence of the adverse effects of irinotecan and raltitrexed in previously heavily treated patients with metastatic colorectal carcinoma.

METHODS

Fifty-six patients received irinotecan (at a dose of 80 mg/m(2) on Days 1, 8, 15, and 22 every 5 wks), combined with raltitrexed (at a dose of 3 mg/m(2) every 3 wks). Genotyping for the MTHFR C677T polymorphism, the TATA box region in the UGT1A1 promoter, and tandem repeats in the TS promoter was performed on genomic DNA extracted from blood. Nineteen variables related to patient, disease, and treatment characteristics, together with genotypes, were analyzed using a binary logistic regression model with stepwise selection to evaluate their correlation with adverse reactions.

RESULTS

Toxicities (determined according to the National Cancer Institute Common Toxicity Criteria) were evaluated in 169 cycles. Grade 3/4 neutropenia was reported to occur in 2% of cycles, Grade 2-4 nausea was reported to occur in 19% of cycles, Grade 2-4 emesis was reported to occur in 9% of cycles, Grade 2-4 diarrhea was reported to occur in 20% of cycles, Grade 2/3 fatigue was reported to occur in 11% of cycles, and Grade 3/4 hepatic toxicity was reported to occur in 7% of cycles. Homozygosis for six TA repeats in the promoter region of the UGT1A1 gene was found to be the main predictive factor for diarrhea (P < 0.00005), emesis (P = 0.0001), and fatigue (P = 0.007). Homozygosis for two tandem repeats in the TS promoter was found to be predictive of a reduced incidence of fatigue (P = 0.044). MTHFR C677T polymorphism was not found to be associated with any adverse reaction.

CONCLUSIONS

In the current study, UGT1A1 promoter polymorphism was found to be predictive of the risk of diarrhea, emesis, and fatigue caused by chemotherapy with irinotecan and raltitrexed. Screening for UGT1A1 promoter polymorphism may be clinically useful for identifying patients at a higher risk of developing a severe or potentially life-threatening toxicity after irinotecan-based chemotherapy.

Collapse

Feliu J, Castañón C, Salud A, Mel JR, Escudero P, Pelegrín A, López-Gómez L, Ruiz M, González E, Juárez F, Lizón J, Castro J, González-Barón M. Phase II randomised trial of raltitrexed-oxaliplatin vs raltitrexed-irinotecan as first-line treatment in advanced colorectal cancer. Br J Cancer 2006;93:1230-5. [PMID: 16265344 PMCID: PMC2361515 DOI: 10.1038/sj.bjc.6602860] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

Santini D, Vincenzi B, La Cesa A, Caricato M, Schiavon G, Spalletta B, Di Seri M, Coppola R, Rocci L, Tonini G. Continuous infusion of oxaliplatin plus chronomodulated capecitabine in 5-fluorouracil- and irinotecan-resistant advanced colorectal cancer patients. Oncology 2005;69:27-34. [PMID: 16088232 DOI: 10.1159/000087285] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2004] [Accepted: 12/12/2004] [Indexed: 11/19/2022]

Abstract

OBJECTIVES

The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients.

METHODS

36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study.

TREATMENT

Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1-14 every 21 days. 16 (44.4%) patients had previously received only 1 chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy lines. Moreover, 12 patients (33.3%) progressed after a first or second line of oxaliplatin-based regimen as well.

RESULTS

Most frequent related G3-4 adverse reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%), mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3-4 anemia, leucopenia and liver toxicities were not observed. The overall response rate was 30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%) and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant patients, the overall response rate was 25% (3 patients); 6 patients (54.5%) obtained a stable disease, and only 3 patients (25%) progressed. The median overall survival was 11.3 months (95% confidence interval 7.0-15.7 months), the median response duration 2.8 months (95% confidence interval 1.2-5.6 months) and the median time to progression 6.7 months (95% confidence interval 5.7-6.3 months). The 1-year survival rate was 53.8%.

CONCLUSIONS

The high overall tumor growth control, the remarkable median time to progression and overall survival and the good safety profile are of particular interest for patients with heavy pretreated metastatic CRC.

Collapse

Lin WL, Li DG, Chen Q, Lu HM. Clinical and experimental study of oxaliplatin in treating human gastric carcinoma. World J Gastroenterol 2004;10:2911-5. [PMID: 15334700 PMCID: PMC4572132 DOI: 10.3748/wjg.v10.i19.2911] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open

Abstract

AIM: To evaluate the therapeutic effectiveness of oxaliplatin on human gastric carcinoma and to explore its mechanisms.

METHODS: Twenty-two cases of stage IV gastric carcinoma received 4-6 (mean 4.6) cycles of first line combined chemotherapy with oxaliplatin (oxaliplatin 85 mg/m², iv, gtt, 1 h, d 1; leukovorin 200 mg/m², iv, gtt, 1 h, d 1 and d 2; 5-FU 300 mg/m²,iv, d 1 and d 2, 5-FU, continuous iv, gtt, 48 h; 1 cycle/2 wk). Response rate, progression-free survival (PFS), total survival time, toxic side effects were evaluated. The inhibitory effect of oxaliplatin on human gastric cell line SGC-7901 was detected and IC₅₀ was calculated by MTT. Transmission electron microscopy, flow cytometry and TUNEL were performed to evaluate the apoptosis of cell line induced by the drug. The expression of Caspase-3 m-RNA was detected by RT-PCR. AC-DEVD-CHO, a Caspase-3 specific inhibitor, was used to elucidate the role of activated Caspase-3 in the process of apoptosis induced by oxaliplatin.

RESULTS: Total response (complete and partial) occurred in 9 (40.9%) patients. Mean PFS was 4.2 mo and mean total survival time was 7.2 mo. Cumulative neurotoxicity (all grade I-II), vomiting and diarrhea, myelosuppression appeared in 93.5%, 20%, 32.9% patients, respectively. IC₅₀ was calculated to be 0.71 mg/L by MTT assay. A maximal inhibitory rate reached 85.3%. Apoptosis index was elevated after incubated with 1 mmol/L oxaliplatin for 30 min, but without statistic significance (P > 0.05). However it could be detected at a much higher degree both by flowcytometry and by TUNEL with a statistical significance (68.47% ± 7.92% and 8.23% ± 2.67%, respectively, P < 0.05) after incubated with 1 mmol/L oxaliplatin for 2 d. By means of RT-PCR, we detected an enhancement of Caspase-3 m-RNA expression induced by oxaliplatin which was also in positive correlation with the apoptotic level. AC-DEVD-CHO, a Caspase-3 specific inhibitor, could significantly inhibit and delay apoptosis induced by oxaliplatin.

CONCLUSION: Oxaliplatin is effective and well-tolerated in patients with advanced gastric carcinoma. Oxaliplatin could significantly inhibit the growth of human gastric cell line SGC-7901. The induction of Caspase-3 m-RNA expression, activation of Caspase-3 and promotion of apoptosis may be some of the therapeutic mechanisms of oxaliplatin on gastric carcinoma. Annexin-V-fluorescein labeling flow cytometry is much more sensitive than TUNEL in detecting early stage apoptosis.

Collapse