The addition of bevacizumab to fluoropyrimidine, irinotecan and oxaliplatin-based therapy improves survival for patients with metastatic colorectal cancer (CRC): Combined analysis of efficacy

Popov, I; Milićević, Miroslav; Radošević-Jelić, Ljiljana

doi:10.2298/aci0804011p

Cited by 8 publications

(5 citation statements)

References 12 publications

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“…Increases in the rate of response (44.8% vs 34.8% ( Hurwitz, 2004 ); 45% vs 35% ( Popov, 2008 )), smaller than those described in our study, and very similar PFS (10.6 vs 6.2 months ( Hurwitz, 2004 ); 11 vs 6.5 months ( Popov, 2008 )) and OS (20.3 vs 15.6 months ( Hurwitz, 2004 ); 20 vs 15 months ( Popov, 2008 )) were obtained in clinical trials that added bevacizumab to IFL regimens, representing a significant improvement compared with the group treated with IFL only. Even better results have recently been reported from a single-arm phase II trial, in which FOLFIRI+bevacizumab administration achieved a response rate of 65%, and a median PFS and OS of 12.8 and 31.3 months, respectively ( Kopetz et al , 2010 ).…”

Section: Discussionmentioning

confidence: 99%

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer

et al. 2010

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Background:Combination of bevacizumab and FOLFIRI has currently become one of the standard therapeutic regimens. However, published information is still limited. The objective of the present retrospective observational study is to analyse the response and toxicity of first-line treatment with FOLFIRI+bevacizumab in patients with metastatic colorectal cancer (mCRC).Methods:Data were collected from patients from nine Spanish sites diagnosed with mCRC, ECOG⩽2, whose first treatment for advanced disease was at least three cycles of FOLFIRI+bevacizumab.Results:A total of 95 patients were enrolled into the study: 64.2% males, median age of 59 years (53.2–67.1 years), ECOG=0–1 in 96.9% of patients. The main site of primary tumour was the colon (69.7%), and most metastases occurred in the liver (71.6%). Clinical benefit was detected in 67.4% (57.0–76.6; 95% confidence interval (CI)), with 8.4% of CR and 42.1% of PR. Median TTP was 10.6 months (10.0–11.3; 95% CI), PFS was 10.6 months (9.8–11.3; 95% CI), and OS was 20.7 months (17.1–24.2; 95% CI). Main grade I–II toxicities included haematological toxicity (35.8%), diarrhea (27.3%), mucositis (25.3%), asthenia (19.0%), haemorrhages (11.6%), and emesis (10.6%). Toxicities reaching grades III–IV were haematological toxicity (9.5%), diarrhea (8.5%), mucositis (5.3%), hepatic toxicity (2.1%), asthenia (2.1%), proteinuria (1.1%), emesis (1.1%), pain (1.1%), and colics (1.1%).Conclusion:Results of this study support the beneficial effect of adding bevacizumab to FOLFIRI regimen in terms of efficacy and show a favourable tolerability profile.

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Section: Discussionmentioning

confidence: 99%

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer

et al. 2010

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“…As the antitumor activity of these agents originates from anti-angiogenesis or the inhibition of growth signals, and thus differs from that of traditional chemotherapeutic agents, these targeted agents reportedly enhance antitumor activity when used in combination with chemotherapy by means of their different mechanisms (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice

Nukatsuka

Saitô

Nakagawa

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. In this study, combination therapies using the oral fluoropyrimidine tegafur-gimeracil-oteracil (S-1) with several targeted agents or antibodies, were evaluated. First, the effects of tyrosine kinase inhibitors (erlotinib hydrochloride, sorafenib tosilate and sunitinib malate) against human nonsmall cell lung cancer (NSCLC), breast cancer and colorectal cancer were evaluated in vivo. The effects of the combination of S-1 and targeted antibodies (bevacizumab and cetuximab) against human colorectal cancers was also evaluated in vivo. S-1 and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib, showed a significant inhibition of growth in human NSCLC (Lu-99 and PC-9 cell lines). The antitumor activity of the combination of S-1 and erlotinib against Lu-99 and PC-9 cancer cell lines was significantly superior to either monotherapy (P<0.05). Combination therapy using the multi-tyrosine kinase inhibitors, sorafenib or sunitinib, with S-1 against breast cancer (MX-1 cell line) and NSCLC (NCI-H460 cell line) was significantly superior to either monotherapy (P<0.01). The combination of the anti-vascular endothelial growth factor antibody bevacizumab or the anti-EGFR antibody, cetuximab, with S-1 against human colorectal cancer [Col-1, KM20C (bevacizumab) and DLD-1 (cetuximab) cell lines] and a 5-fluorouracil (5-FU)-resistant cell line (KM12C/5-FU) was significantly superior to either monotherapy (p<0.01). In particular, the growth of the Col-1 cells was completely inhibited by the combination of S-1 and bevacizumab. No toxic mortalities and no significant difference in the body weight changes of the animals treated with S-1 combined with the targeted agents or with the monotherapies were observed; therefore, the treatments appeared to be well-tolerated. Our preclinical findings indicate that the combination therapies of S-1 and targeted agents are promising treatment options. IntroductionNew targeted agents, i.e., targeted antibodies and tyrosine kinase inhibitors, have been developed and used clinically against various cancers (colorectal, lung, kidney and breast cancer, etc.). As the antitumor activity of these agents originates from anti-angiogenesis or the inhibition of growth signals, and thus differs from that of traditional chemotherapeutic agents, these targeted agents reportedly enhance antitumor activity when used in combination with chemotherapy by means of their different mechanisms (1-5).Tegafur-gimeracil-oteracil (S-1), an oral fluoropyrimidine, is composed of 1 M tegafur [a masked form of 5-fluorouracil (5-FU)], 0.4 M 5-chloro-2, 4-dihydroxypyrimidine [gimeracil, a potent inhibitor of the 5-FU degradation enzyme dihydropyrimidine dehydrogenase (DPD) in the liver and tumor tissues] and 1 M potassium oxonate (oteracil, which mainly inhibits the phosphorylation of 5-FU in the gastrointestinal tract) (7). S-1 has been clinically shown to be effective against various human cancers (8) and to have a potent antitumor efficacy, with a low gastrointestinal toxicity, against var...

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“…The rate of patient response to treatment with irinotecan is low 1,3,4,6,8 and it is typically used clinically in combination with other drugs such as 5-fluorouracil or anti-tumor antibodies. Depending on the type of tumor and the combination therapy, reported response rates range from 20 to 50%.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biodistribution of [¹¹C]SN‐38

Apana¹,

Anderson

Berridge

2010

Labelled Comp Radiopharmac

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a,cÃ -hydroxy camptothecin) is a topoisomerase I inhibitor that is the active chemotherapeutic agent of irinotecan, indicated for colon cancer. Because the rate of response to irinotecan treatment is low, it is of interest to have a prognostic indicator to identify and more selectively treat those who are likely to respond to treatment. We have therefore prepared SN-38 labeled with carbon-11. SN-38 was prepared by radical oxidation of 3-[ 11 C]propionaldehyde and subsequent radical addition of the ethyl fragment to 10-hydroxycamptothecin. Labeled propionaldehyde was prepared by reaction of methyl iodide with 2-lithiomethyl-1,3-dioxolane. Overall chemical yield was 34% from carbon dioxide. The murine biodistribution and radiation dosimetry of [11 C]SN-38 was measured by PET scanning in preparation for initial human studies. Biodistribution was fairly uniform except for hepatobiliary and urinary excretion.

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The addition of bevacizumab to fluoropyrimidine, irinotecan and oxaliplatin-based therapy improves survival for patients with metastatic colorectal cancer (CRC): Combined analysis of efficacy

Cited by 8 publications

References 12 publications

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer

Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice

Synthesis and biodistribution of [¹¹C]SN‐38

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The addition of bevacizumab to fluoropyrimidine, irinotecan and oxaliplatin-based therapy improves survival for patients with metastatic colorectal cancer (CRC): Combined analysis of efficacy

Cited by 8 publications

References 12 publications

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer

A retrospective observational study on the safety and efficacy of first-line treatment with bevacizumab combined with FOLFIRI in metastatic colorectal cancer

Combination therapy using oral S-1 and targeted agents against human tumor xenografts in nude mice

Synthesis and biodistribution of [11C]SN‐38

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Synthesis and biodistribution of [¹¹C]SN‐38