Safety analysis of two different regimens of uracil–tegafur plus leucovorin as adjuvant chemotherapy for high-risk stage II and III colon cancer in a phase III trial comparing 6 with 18 months of treatment: JFMC33-0502 trial

PURPOSE: The JFMC33-0502 trial is a phase III clinical study designed to determine the most appropriate duration of postoperative adjuvant chemotherapy with uracil–tegafur (UFT) plus leucovorin in patients with stage IIB or III colon cancer. We report the interim results of preplanned safety analyses. METHODS: Patients with stage IIB or III colon cancer who had undergone curative resection were randomly assigned to receive UFT (300 mg/m(2)) plus leucovorin (75 mg/day) for 6 months (control group, 4 weeks of treatment followed by a 1-week rest, five courses) or for 18 months (study group, 5 days of treatment followed by a 2-day rest, 15 courses). Treatment status and safety were evaluated. RESULTS: A total of 1,071 patients were enrolled, and 1,063 were included in safety analyses. Treatment completion rate at 6 months was 74.0 % in the control group and 76.7 % in the study group. Treatment completion rate in the study group at 18 months was 56.0 %. The overall incidence of adverse events (AEs) was 75.3 % in the control group and 77.6 % in the study group. The incidences of grade 3 or higher AEs were low in both groups. During the first 6 months, the incidences of the subjective AEs were significantly lower in the study group. CONCLUSIONS: Oral UFT plus leucovorin given by either dosage schedule is a very safe regimen for adjuvant chemotherapy. In particular, 5 days of treatment followed by a 2-day rest was a useful treatment option from the viewpoint of toxicity even when given for longer than 6 months. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00280-014-2461-5) contains supplementary material, which is available to authorized users

Dating deformation using sheared leucogranite: temporal constraints by ⁴⁰Ar/³⁹Ar thermochronology for the Mae Ping shear zone, NW Thailand

The Mae Ping shear zone (MPSZ) is one of the major ductile strike-slip systems associated with the Cenozoic extrusion tectonics in Southeast Asia. However, its sinistral shear lacks a robust temporal constraint. This study attempts to acquire the deformation timing by applying 40Ar/39Ar thermochronology on a sheared pegmatitic leucogranite showing sinistral S–C fabrics with a thrust component. The contact of the leucogranite sub-paralleling to the major foliation in host gneiss indicates it could be a pre- to syn-shearing intrusion. Most minerals, including garnet, muscovite, K-feldspar, albite, and quartz, exhibit ductile to brittle deformation. Mineral microstructural analysis suggests a retrograde sinistral shear from > 600 to 250 °C. In situ 40Ar/39Ar dating on muscovite yield ages mainly within 42–38 Ma with calculated closure temperatures of 435–330 °C. Fine-grained muscovite aggregates are slightly older than fish, implying that grain size reduction may not always reset 40Ar/39Ar ages. The K-feldspar 40Ar/39Ar step heating age spectrum with two segments of contiguous steps at 24.5 and 35.4 Ma may reflect the coexistence of high-T porphyroclast and low-T K-rich fine-grain recrystallizing at pressure shadows. The reconstructed cooling path and inferred deformation temperatures constrain a shear duration of 42–30 Ma for the MPSZ. The activation of the MPSZ before 42 Ma could be linked to the Eocene metamorphism within a transpressional regime triggering crustal thickening that may further induce the leucogranitic melt. This study also shows leucogranite can be a nice thermal history recorder for a shear zone regarding its petrogenesis and suitable mineral assemblage for thermochronology