Development of a synchrotron biaxial tensile device for in situ characterization of thin films mechanical response.

We have developed on the DIFFABS-SOLEIL beamline a biaxial tensile machine working in the synchrotron environment for in situ diffraction characterization of thin polycrystalline films mechanical response. The machine has been designed to test compliant substrates coated by the studied films under controlled, applied strain field. Technological challenges comprise the sample design including fixation of the substrate ends, the related generation of a uniform strain field in the studied (central) volume, and the operations from the beamline pilot. Preliminary tests on 150 nm thick W films deposited onto polyimide cruciform substrates are presented. The obtained results for applied strains using x-ray diffraction and digital image correlation methods clearly show the full potentialities of this new setup.

Phase II study of tallysomycin S10b in patients with advanced colorectal cancer.

A total of 16 patients with histologically confirmed colorectal cancer were entered into this phase II trial, designed to evaluate the efficacy and safety of tallysomycin S10b. The compound was given i.v. weekly at a dose of 2.5 mg/m2 by push injection. Pulmonary toxicity was the most significant side effect; it was observed in three patients and required treatment discontinuation in one. Skin lesions occurred in three patients. Other side effects were mild and their relationship to drug administration was ill-defined. No responses were observed in this group of patients, most of whom had received prior therapy.

Phase II study of adriamycin with sequential methotrexate and 5-fluorouracil (AMF) in gastric carcinoma.

The purpose of this study was to evaluate the response rate, methotrexate plasma levels, and toxicity of a three-drug regimen in patients with gastric carcinoma. A total of 37 patients with advanced measurable adenocarcinoma of the stomach were treated with Adriamycin, methotrexate, and 5-fluorouracil (AMF). Adriamycin and methotrexate were given as i.v. infusions on day 1; 24 h following methotrexate administration, patients received an i.v. infusion of 5-fluorouracil concomitantly with oral leukovorin factor (given over 48 h). Methotrexate levels were monitored regularly in all patients, and courses were repeated every 3 weeks. The median dose levels per course were 50 mg/m2 (range, 40-60 mg/m2) for Adriamycin, 1,000 mg/m2 (range, 650-1,250 mg/m2) for 5-fluorouracil, and 500 mg/m2 (range, 160-625 mg/m2) for methotrexate. Of 36 evaluable patients, 8 (22%) achieved an objective response, including 1 complete remission. Stable disease was noted in 11 patients and a minor tumor regression occurred in 1. The median survival duration of all patients was 6 months (range, 2-31+ months). AMF was well tolerated; toxicities were mild to moderate, most frequently involving nausea and vomiting, mucositis, and neutropenia with or without fever. There was no death directly attributable to chemotherapy. Although the AMF regimen used a well-documented preclinical concept of synergism between methotrexate and 5-fluorouracil, response and survival results suggest a modest activity of this combination in patients with gastric cancer. Better preclinical models are necessary for the development of effective combination chemotherapy.

Ifosfamide and mesna: marginally active in patients with advanced carcinoma of the pancreas.

Ifosfamide, an analogue of cyclophosphamide, has therapeutic activity against a wide variety of human malignancies. In a phase II trial in carcinoma of the pancreas, we treated 31 patients who had not received prior chemotherapy with a median ifosfamide dose of 2 g/m2/d (range, 1.5 to 2 g/m2/d) administered intravenously (IV) over one hour for five consecutive days every 3 weeks. 2-mercaptoethane sulphonate (mesna), an acrolein antagonist with known uroendothelial protective properties, was administered IV at a dose of 400 mg/m2 over 15 minutes before the daily dose of ifosfamide and repeated every four hours for two additional doses. Among 30 evaluable patients, one patient achieved a complete remission (26+ months) and another patient had a partial remission (4 months). The median duration of survival of all patients from the start of ifosfamide therapy was only 3 months (range, 1 to 26+ months). Treatments were generally well tolerated. The most common toxic effects included granulocytopenia, nausea and vomiting, malaise, anorexia, and mild hematuria. Mesna offers an adequate protection against uroendothelial injury caused by ifosfamide. Despite the previously reported response rate of greater than 20% at the same or lower doses of ifosfamide in other studies, our data suggest that ifosfamide is only marginally active against cancer of the pancreas and appears to be of minimal value in the treatment of patients with this tumor.