Adjuvant chemotherapy with uracil-tegafur improves survival among patients with completely resected pathological stage I adenocarcinoma of the lung.

This meta-analysis showed that postoperative adjuvant chemotherapy with UFT was associated with improved 5- and 7-year survival in a Japanese patient population composed primarily of stage I adenocarcinoma patients.

Survival was statistically significantly better for patients with completely resected stage I squamous-cell lung carcinoma who were treated with bestatin as a postoperative adjuvant therapy than for those who received a placebo. This result requires confirmation in other phase III trials.

UFT significantly improves survival in patients with stage IA T1b NSCLC compared with surgery alone.

No abstract

We describe novel humanized anti-CD20 monoclonal antibodies (mAbs) developed for therapeutic use on the basis of their physicochemical properties and cellular cytotoxicity. A distinct correlation between apparent dissociation constants (K d ) and apoptotic activity for eight murine anti-CD20 mAbs (OUBM1-OUBM8) and previously-developed murine anti-CD20 mAbs enabled us to categorize anti-CD20 mAbs into two groups. Group A mAbs had lower K d values and did not induce definite apoptosis, while Group B mAbs had greater K d values and did induce definite apoptosis. A murine version mAb of rituximab, 2B8, belongs to Group B. An epitope analysis showed that the epitope of two murine mAbs, OUBM3 and OUBM6, differed from that of 2B8 or 2F2 (ofatumumab). Two mAbs, OUBM3 from Group A and OUBM6 from Group B, were selected and humanized. As expected, the humanized OUBM3 with the lower K d did not induce apoptosis, while the humanized OUBM6 (hOUBM6) with the greater K d did. Both hOU-BM3 and hOUBM6 induced highly-effective, complement-dependent cytotoxicity and antibody-dependent, cell-mediated cytotoxicity against Burkitt's and follicular lymphomas. Importantly, hOUBM6 exhibited cellular cytotoxicity against diffuse, large B cells that are less effectively depleted by rituximab and also exhibited effective cytotoxicity against tumor cells from human CD20(+) leukemia and lymphoma patients. These results suggest the potential impact of the further development of our anti-CD20 mAbs. Our study shows that the selection of mAbs based on their physicochemical parameters, followed by the biological activity assessment for the selected mAbs, is a rational and efficient approach for pharmaceutical mAb development. (Cancer Sci 2010; 101: 201-209) R ecently, the application of immunotherapy using monoclonal antibodies (mAbs) has increased considerably, and numerous mAb candidates are under development or are being assessed in clinical trials. In the case of mAb development using murine mAbs, the degree of complement-dependent cytotoxicity (CDC) and antibody-dependent, cell-mediated cytotoxicity (ADCC) activity can be measured after humanization, which implies that it is difficult to evaluate the clinical effectiveness of these antibodies (Abs) before humanization. The humanization of large numbers of murine mAbs without data to support future clinical use requires massive investments in terms of time, labor, and funding. Furthermore, the evaluation of bioactivity is often dependent on the assay systems themselves. Therefore, it is highly desirable to select candidates for humanization on the basis of the intrinsic parameters of the mAb itself, such as its dissociation constant and epitope, at an early stage of mAb development. In order to establish an efficient and rational method of developing mAbs, we focused on anti-CD20 mAbs as the ideal study target for studying the intrinsic properties of mAbs, because data on these Abs is available.CD20 is a B-cell-specific tetra-transmembrane protein with a molecular weight of 33-37 kDa. It i...

Post-operative UFT administration did not significantly improve post-operative survival of p-stage I NSCLC patients. Subset analyses suggested that UFT might be effective in pT1N0M0 adenocarcinoma patients.

From 1972 to 1990, we treated eight cases of thymic carcinoma (6 squamous cell and 2 small cell carcinomas). According to the classification by Masaoka et al., they consisted of one stage I, four stage III, one stage IVa, and two stage IVb. A complete resection of the primary tumour could be done in only three patients; the others had diagnostic biopsy and then radiation treatment. Four of five patients had a prolonged regression of the primary tumors after irradiation at 40-61.2 Gy. Six patients suffered from extrathoracic metastases. All patients received systemic chemotherapy with different regimens to counter either metastatic or locally recurrent lesions. Only two patients (with a regimen including cyclophosphamide, doxorubicin, and vincristine) obtained a partial response. The median survival of the eight patients was 70 months after surgical operation. The identification of an effective drug combination may thus improve the long-term prognosis of thymic carcinoma since radiotherapy is able to control primary lesions, even in the case of unresectable advanced disease.