768 Efficacy of oral UFT for adjuvant chemotherapy after complete resection of non-small cell lung cancer: Meta-analysis of six randomized trials in 2003 patients

Hamada, Chikuma; Ohta, Mitsuhiko; Wada, Hideho; Fujimura, S.; Kodama, Ken; Imaizumi, Masakazu; Nakanishi, Yoko; Matsuoka, Naoki

doi:10.1016/s1359-6349(03)90793-2

Cited by 5 publications

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“…Recent prospective studies conducted in Japan showed that UFT improves the survival of patients with completely resected NSCLC. [4][5][6] However, the reason for the efficacy of postoperative UFT administration for NSCLC remained unclear, because experimental and clinical studies showed that 5-FU had minimal cytotoxic activity against primary lung cancer. Recently, it has been experimentally demonstrated that GHB and GBL, metabolites of UFT other than 5-FU, can inhibit angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Angiogenesis and the efficacy of postoperative administration of UFT in pathologic stage I non‐small cell lung cancer

et al. 2004

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UFT is an oral 5-fluorouracil derivative drug that may improve postoperative survival in non-small cell lung cancer (NSCLC), and experimental studies have shown that UFT inhibits tumor angiogenesis. In the present study, therefore, the correlation between tumor angiogenesis (intratumoral microvessel density, IMVD) and the efficacy of UFT in 162 patients with pathologic stage I NSCLC was examined. For higher IMVD tumors (IMVD ≥ ≥ ≥ ≥20, n = = = =80), the 5-year survival rate of UFT-treated patients (82.5%) was significantly higher than that of surgery-alone patients (61.8%, P = = = =0.032). For lower IMVD tumors (n = = = =82), however, there was no difference in the survival between these groups (5-year survival rates, 84.9% and 82.6%, respectively; P = = = =0.657). ostoperative prognosis of patients with completely resected non-small cell lung cancer (NSCLC) is not satisfactory. 1)Many prospective studies on the effect of postoperative adjuvant therapy have been conducted, but most studies failed to demonstrate efficacy, although a recent prospective study indicated that cisplatin-based chemotherapy improved the postoperative survival.2, 3) Recently, some prospective randomized studies have demonstrated that postoperative administration of UFT, an oral 5-fluorouracil (5-FU) derivative drug, can improve survival. 4,5) In a prospective randomized study conducted by the West Japan Study Group for Lung Cancer Surgery, the 5-year survival rate of patients with completely resected pathologic (p-) stage I-III NSCLC who received postoperative UFT administration (400 mg/body/day for 1 year after surgery) was 64.1%, which was significantly higher than that of patients who received surgery alone (49.0%, P=0.019).4) In a large-scale prospective randomized study conducted by the Japan Lung Cancer Research Group, a total of 999 p-stage adenocarcinoma patients were randomized to receive either UFT administration for 2 years or no drug (surgery alone), and the UFT-treated patients showed a significantly better survival (P=0.036).5) The efficacy of postoperative UFT administration for NSCLC has recently been confirmed by a meta-analysis of six randomized trials in 2003 patients; postoperative UFT administration improved the overall survival of completely resected NSCLC patients (hazard ratio, 0.77; P=0.011). 6)UFT is an anti-tumor agent composed of tegafur (1-[2-tetrahydrofuryl]-5-fluorouracil, FT) and uracil (U) at a molar ratio of 1:4; FT is a pro-drug that persistently releases 5-FU, and uracil is added to inhibit degradation of the released 5-FU. 7,8) Thus, it is generally believed that the anti-tumor activity of UFT is derived from released 5-FU. Recently, Yonekura and coworkers demonstrated that UFT and its metabolites, γ-hydroxybutyric acid (GHB) and γ-butyrolactone (GBL), inhibited tumor angiogenesis.9) In the present study, therefore, we assessed the correlation between the efficacy of postoperative UFT administration and tumor angiogenesis in resected NSCLC. In a previous study, we had used a pan-endothelial marker, CD...

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Section: Discussionmentioning

confidence: 99%

Angiogenesis and the efficacy of postoperative administration of UFT in pathologic stage I non‐small cell lung cancer

et al. 2004

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“…[5][6][7][8][9][10] However, recent mega trials have introduced epoch-making changes for postoperative adjuvant chemotherapy in clinical practice since ASCO 2003. [11][12][13][14][15][16][17][18][19] The new paradigm shift for the adjuvant treatment after surgery is demonstrated here by the Japanese and international trials that have been reported since 2003.…”

Section: Introductionmentioning

confidence: 99%

Postoperative adjuvant therapy for completely resected early-stage non-small cell lung cancer

et al. 2005

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Consensus on adjuvant therapy for completely resected non-small cell lung cancer until 2002 was as follows. (1) There was no significant impact of postoperative adjuvant chemotherapy based on meta-analysis and previous clinical trials. (2) Confirmatory studies are necessary in large-scale prospective clinical trials. However, recent mega trials have introduced epoch-making changes for postoperative adjuvant chemotherapy in clinical practice since ASCO 2003. The effectiveness of UFT in N0 patients was confirmed. Patients with completely resected stage I non-small cell lung cancer, especially T2N0 adenocarcinoma, will benefit from adjuvant chemotherapy with UFT. The results of the International Adjuvant Lung Trial (IALT) have confirmed the meta-analysis in 1995. Also, both the JBR10 and Cancer and Leukemia Group B (CALGB) 9633 studies have also confirmed positive IALT results of the benefit for postoperative platinum-based chemotherapy in completely resected non-small cell lung cancer. Adjuvant chemotherapy for pathological stage IB to II, completely resected non-small cell lung cancer is standard care based on clinical trials. UFT showed the strongest evidence for IB in Japan. Platinum doublet chemotherapy with third-generation anticancer agents is also recommended. Adjuvant chemotherapy should be offered as standard care to patients after completely resected early stage non-small cell lung cancer. However, there is no evidence of the feasibility and efficacy for adjuvant chemotherapy with the platinum-based regimen in Japan. Careful management should be necessary in such treatment.

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“…1 Although the propensity of non-small-cell lung cancer to metastasize early is well recognized, there is no convincing evidence that postoperative radiotherapy or adjuvant chemotherapy improves survival in stage I disease. 6 It is against this background that the study re-ported by Kato and colleagues 7 in this issue of the Journal is of interest. 1 Many of the relatively small studies that have suggested that chemotherapy can improve survival in non-small-cell lung cancer 2,3 used the same agents that have proved useful in advanced disease, such as cisplatin, an agent generally recognized as one of the most active in non-small-cell lung cancer.…”

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confidence: 98%

Adjuvant Chemotherapy for Adenocarcinoma of the Lung — Is the Standard of Care Ready for Change?

Diasio¹

2004

N Engl J Med

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768 Efficacy of oral UFT for adjuvant chemotherapy after complete resection of non-small cell lung cancer: Meta-analysis of six randomized trials in 2003 patients

Cited by 5 publications

References 0 publications

Angiogenesis and the efficacy of postoperative administration of UFT in pathologic stage I non‐small cell lung cancer

Angiogenesis and the efficacy of postoperative administration of UFT in pathologic stage I non‐small cell lung cancer

Postoperative adjuvant therapy for completely resected early-stage non-small cell lung cancer

Adjuvant Chemotherapy for Adenocarcinoma of the Lung — Is the Standard of Care Ready for Change?

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