[en] The possible interaction of 5-fluorouracil (5-FU) and irradiation on mouse lip mucosa was studied, with special interest for the influence of the route of administration of the drug, either by single intraperitoneal (i.p.) injection or by 7 days continuous subcutaneous infusion. Apart from the possible modification by the drug of radiation-induced damage to the lip mucosa assessment was made of the systemic toxicity. No modification of the radiosensitivity of mouse lip mucosa nor of its repair capacity was observed with the use of 5-FU given either by i.p. injection or by continuous infusion. However, the combination of 5-FU and irradiation resulted in an increased systemic toxicity which was only seen when 5-FU was administered by an i.p. injection in close timing with irradiation. It is suggested that this increased systemic toxicity is caused by the combined effects of irradiation and 5-FU on the alimentary tract, although the mechanism could not be demonstrated. 27 refs.; 5 figs.; 2 tabs

[en] Objective: Since 1979, our institution has treated locally advanced rectal cancer with preoperative irradiation followed by resection with or without intraoperative radiation therapy (IORT). In 1986, our preoperative treatment policy was changed to include bolus 5-FU chemotherapy concurrent with irradiation in hopes of improving resectability, downstaging and/or local control rates. We report the long-term results with the addition of 5-FU chemotherapy to preoperative irradiation. Materials and Methods: From 1979 - 1994, 200 patients with locally advanced rectal carcinoma (primary or recurrent) received preoperative irradiation, resection and IORT if indicated. Bolus 5-FU (500mg/m²/day) chemotherapy was administered for three days during weeks one and five of irradiation. The change in treatment policy was limited to the addition of 5-FU chemotherapy: the radiation techniques (four-field), doses (50.4 Gy), and indications for intraoperative radiation (microscopic residual, gross residual, tumor adherence) remained constant. The median follow-up for the entire group of patients was 33 months (.95 months - 199 months), and the minimum follow-up was 1.5 years. Tabular results are 5-year actuarial calculations. Results: One hundred and five patients received preoperative 5-FU chemotherapy and irradiation whereas 95 patients underwent preoperative irradiation alone. Sixty-five percent of the patients were able to undergo complete resections, and 53% had transmural disease upon pathologic examination. The addition of chemotherapy did not affect the rates of resectability or tumor downstaging. However, the 10-year local control rate was significantly improved for those patients who received preoperative chemotherapy: 77% vs. 44% (p<0.01) (see figure). When stratified by extent of resection and stage, those patients who underwent complete resections or had transmural disease had significantly improved local control rates when compared to the non-chemotherapy group: No difference in survival was seen based on the administration of chemotherapy. Conclusions: With long-term follow-up, the addition of 5-FU chemotherapy provides a significant local control benefit for patients presenting with locally advanced rectal carcinoma. The benefit was limited to those patients with complete resections and transmural disease. This finding supports escalating the role of 5-FU chemotherapy: firstly, with continuous infusion concurrent with irradiation; and secondly, with maintenance therapy postoperatively

[en] For the locally evolved larynx cancers the docetaxel-cisplatin-5-fluoro-uracil schema has demonstrated a significant superiority in terms of global response in comparison with cisplatin-5-fluoro-uracil schema. The docetaxel--cisplatin-5-fluoro-uracil outline would seem to be better tolerated that the P.F. schema and the preliminary results suggest that the larynx preservation rate is higher among patients treated by docetaxel-cisplatin-5-fluoro-uracil. (N.C.)

[en] Although the combination of chemotherapy and surgical resection has effectively increased the survival rate of colorectal cancer patients in recent decades, acquired drug resistance is still a problem that leads to treatment failure. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has recently been reported to show anticancer effects against numerous types of cancer, including colorectal cancer. This study showed that DHA exerted a strong anticancer effect against several colorectal cancer cell lines. We also found that p53 knockout colorectal cancer HCT116 cells (HCT116 TP53^−/−) were not sensitive to 5-fluorouracil (5-FU) treatment, unlike wild-type HCT116 cells. Interestingly, co-treatment with DHA could effectively restore the anticancer effect of 5-FU against HCT116 TP53^−/− cells, which manifested as the inhibition of proliferation and induction of reactive oxygen species (ROS)-mediated apoptosis and was accompanied by the upregulation of B-cell lymphoma 2 (BCL-2) and downregulation of the BCL-2-associated X protein (BAX). These findings suggested that DHA could effectively sensitize cells to 5-FU through ROS-mediated apoptosis and the alteration of the BCL-2/BAX expression ratio, which indicated that this may be one of the mechanisms of the DHA-promoted 5-FU anticancer effect.

[en] The authors have concluded that the chemotherapy was superior to the two other strategies in term of local control of the disease and larynx conservation. They added that even if it did not make an advantage in term of survival, the chemotherapy must be considered among the patients wanting to keep their larynx as a standard and the laryngectomy as a catching up treatment. This recommendation does not apply if there is a significant attack of the tongue base or a cartilaginous destruction. (N.C.)

[en] Highlights: • Uridine triacetate reduced mortality from 5FU overdose and DPD deficiency. • Treatment within 24 h conferred the greatest protection against 5FU overexposure. • Delaying uridine triacetate administration led to greater toxicity and mortality. • Little benefit was observed when uridine triacetate was given 96–120 h after 5FU. • Results support clinical evidence of reduced 5FU/capecitabine mortality and toxicity. Uridine triacetate has been shown to be an effective antidote against mortality and toxicity caused by either overdoses or exaggerated susceptibility to the widely used anticancer agents 5-fluorouracil (5-FU) and capecitabine. However, a direct assessment of efficacy based on when emergency treatment was initiated was not clinically feasible. In this study we used mouse models of 5-FU overdose and of dihydropyrimidine dehydrogenase (DPD) deficiency to compare the efficacy of uridine triacetate in reducing toxicity and mortality when treatment was initiated at time points from 4 to 144 h after administration of 5-FU. We found that uridine triacetate was effective both in the 5-FU overdose and DPD deficiency models. Starting treatment within 24 h was most effective at reducing toxicity and mortality in both models, while treatment starting more than 96 to 120 h after 5-FU was far less effective. Uridine triacetate also reduced mortality in the DPD deficiency model when mice were treated with the 5-FU prodrug capecitabine. The results of this study are supportive of clinical observations and practice, indicating that efficacy declined progressively with later and later treatment initiation. Prompt treatment with uridine triacetate, within 24 h, conferred the greatest protection against 5-FU overexposure.

[en] Using non-linear solvent response of binary mixture, control over a small metabolite fibril (5-Fluorouracil, 5-FU) is achieved. Specific fibrillar structures of 5-FU exhibit a great potential to modulate live cell membrane fluidity and model membrane lipid distribution. (author)

[en] The neo adjuvant chemotherapy and the concomitant associations chemo-radiotherapy are new therapeutic approaches of invasive bladder cancers, which should have to bring a benefit in term of local control, life length and quality. These two strategies aren't incompatible. Some people have joined one neo adjuvant chemotherapy prior to one radio chemotherapy association ± cystectomy. 60 refs., 7 tabs

[en] This book contains 15 chapters. Some of the titles are: Combined effects of radiation, ACNU, and 5-fluorouracil on gliomas: An experimental combination therapy; A study of intratumoral oxygen pressure in brain tumors; An outline of RAFP therapy; Epidemiology and statistical analysis of gliomas; and Statistical considerations of therapeutic results in glioblastoma

[en] The good results got after chemoradiotherapy are confirmed. The quality of tumoral response after the first series of irradiation is probably the most powerful factor of independent prediction of survival in complete remission. (N.C.)