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[en] Purpose: The optimal chemotherapy regimen remains undefined in the treatment of locally advanced oropharyngeal cancer by concomitant chemoradiation. This article compares two platinum-based chemotherapy regimens. Methods and Materials: In this retrospective study, we reviewed all consecutive patients treated for Stage III or IVA-B oropharyngeal cancer using either a combination of carboplatin and 5-fluorouracil (5FU) every 3 weeks or high-dose cisplatin every 3 weeks concomitant with definitive radiation therapy. Results: A total of 200 patients were treated with carboplatin-5FU and 53 patients with cisplatin. Median potential follow-up was 43 months. The 3-year overall survival rates for carboplatin-5FU and cisplatin respectively were 79.1% and 74.9% (p = 0.628), the 3-year disease-free survival rates were 76.0% and 71.3% (p = 0.799), and the 3-year locoregional control rates were 88.4% and 94.2% (p = 0.244). Conclusions: We could not demonstrate differences between these two regimens, which both proved efficacious. Polychemotherapy and monochemotherapy therefore seem comparable in this retrospective analysis.
[en] The site of attack of OH radicals on dihydrouracil and five methylated derivatives was determined by pulse radiolysis using N,N,N',N'-tetramethylphenylenediamine (TMPD) to detect oxidizing radicals and tetranitromethane (TNM) as well as K3Fe(CN)6 to detect reducing radicals. In dihydrouracil OH radicals abstract preferentially an H atom at C(6) giving the 6-yl radical (>= 90 %) which at pH equivalent to 6.5 reduces TNM and K3Fe(CN)6 at almost diffusion-controlled rates. Only a small fraction of OH radicals abstract the H atom at C(5) (<= 10%). The resulting 5-yl radical oxidizes TMPD to TMPD+ at pH 7-8. With the methylated derivatives of dihydrouracil, OH radicals react less selectively, especially in the case of N(1)-methyl derivatives. This methyl group is activated to a similar degree as the methylene group at C(6). In 1-Medihydrouracil the yield of N(1)-CH2 radicals is about 29%. Radicals at the other methyl substituents are generated to a lesser extent (<= 10%) and are relatively unreactive towards oxidizing agents such as TNM and K3Fe(CN)6 as well as towards the reducing agent, TMPD. Although methyl substitution opens new routes for OH attack the preferred site of H abstraction remains C(6) (> 60%). (author)
[en] Purpose: To evaluate the long-term efficacy of concurrent radiotherapy with mitomycin-C (MMC)-based or cisplatin (CP)-based combinations in a cohort of patients with locally advanced anal canal carcinoma. Methods and Materials: Between 1988 and 2000, 179 patients with locally advanced anal canal carcinoma were treated at the Instituto Nacional de Cancer with two cycles of chemotherapy during Weeks 1 and 5 of radiotherapy. 5-Fluorouracil (750 mg/m2 120-hour infusion or 1,000 mg/m2 96-hour infusion) plus CP (100 mg/m2) on the first day of each cycle or MMC (10-15 mg/m2) on the first day of Cycle 1 was administered concurrent with radiotherapy (total dose, 55-59.4 Gy). Of the 179 patients, 60% were included from a randomized trial initiated at the Instituto Nacional de Cancer in 1991 that compared concurrent chemoradiotherapy with MMC vs. CP. Results: The median follow-up for the whole chemoradiotherapy group was 83 months. The median patient age was 58 years, 57% had Stage T3-T4 tumors, and 35% had N-positive disease. The 5-year cumulative colostomy rate was not significantly different between the CP group (22%) and MMC group (29%; p = .28). The actuarial 10-year overall survival and disease-free survival rate for the CP group was 54% and 49% and for the MMC group was 52% and 53%, respectively (p = .32 and p = .92, respectively). On multivariate analysis, male gender (p = .042) and advanced Stage T3-T4 disease (p <.0001) were statistically significant for worse disease-free survival. Stage T3-T4 (p = .039) and N+ (p = .039) disease remained independently significant for overall survival. Conclusion: Long-term follow-up has confirmed the good results of chemoradiotherapy with CP plus 5-fluorouracil, which seem to provide results equivalent to those with MMC plus 5-fluorouracil.
[en] In this paper, the results of our studies on the catalyst-free synthesis of some new 6-aminouracils bearing naphthoquinone, benzo[a]phenazine, benzo[f]pyrido[2,3-b]quinoxaline, and benzo[f]quinoxaline substituents are reported. At first, 6-amino-5-(3,4-dioxo-1-naphthalenyl)uracil derivatives were synthesized from the reaction of various 6-aminouracils with 1,2-naphthoquinone in DMSO at 70 °C in good to excellent yields. Subsequently, the prepared 6-amino-5-(3,4-dioxo-1-naphthalenyl)uracils were subjected to the condensation reaction with various vicinal diamines, in chloroform under reflux conditions to synthesize 6-aminouracils bearing benzo[a]phenazine, benzo[f]pyrido[2,3-b]quinoxaline, and benzo[f]quinoxaline derivatives. Graphical abstract: .
[en] Ab initio calculations were performed to determine the identity of a radical produced in the radiolysis of aqueous solutions of uracil. The radical in question can be produced in basic solution by .OH attack at the C6 position of uracil or in neutral solution by a mechanism involving ionization by SO4- and subsequent deprotonation. Proposed structures include a ring-opened radical 3 and a ring-closed radical 4. Calculations were made on various conformations of 3 as well as on 4 and two isomers of 4. Comparison with the experimental isotropic hyperfine coupling constants, as well as energetic considerations, clearly point to 4 as being the radical actually observed
[en] The reaction of [3-2H1]propiolic acid with urea provides a simple route to [6-2H1]uracil, and further exchange with DC1 affords [5,6-2H2]uracil. Reaction of the meso and d,1-isomers of [2,3-2H2]succinamide with lead tetraacetate leads to the cis and trans isomers of [5,6-2H2]5,6-dihydrouracil. (author)
[en] To examine the long-term outcomes of alternating chemoradiotherapy (ALCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to assess the efficacy of ALCRT for NPC. Patients with stage IIB to IVB, ECOG PS 0–2, 18–70 years-old, and sufficient organ function were eligible for this study. First, chemotherapy, consisting of 5-fluorouracil (800 mg/m2 per 24 h on days 1–5) and cisplatin (100 mg/m2 per 24 h on day 6), was administered, then a wide field of radiotherapy (36 Gy/20 fraction), chemotherapy, a shrinking field of radiotherapy (34 Gy/17 fraction), and chemotherapy were performed alternately. Between December 2003 and March 2006, 90 patients in 25 facilities were enrolled in this study, 87 patients were finally evaluated. A total of 67 patients (76.1%) completed the course of treatment. The overall survival and the progression-free survival rates at 5 years were 78.04% (95% CI: 69.1∼87.0%), and 68.74% (95% CI: 58.8∼78.7%), respectively. The long-term outcomes of ALCRT for NPC were thought to be promising. ALCRT will be considered to be a controlled trial to compare therapeutic results with those of concurrent chemoradiotherapy for NPC
[en] Carcinoma of the prostate gland is the most frequent malignant tumour affecting male population. While the large majority of tumours is represented by adenocarcinoma, pure squamous cell carcinoma comprises only 0,5–1% of all prostate neoplastic lesions. It is characterised by a high degree of malignancy, commonly metastasising to the bone (mainly with osteolytic lesions), liver and lungs with a median survival time of 14 months. Several therapeutic approaches have been employed in the effort to treat prostate pure squamous cell carcinoma, including radical surgery, radiotherapy, chemotherapy and hormonal therapy. All of them mostly failed to gain a significant survival benefit. We herein report on a case of pure squamous cell carcinoma of the prostate approached with combined-modality treatment, with the administration of 3 courses of cisplatin 75 mg/m"2 on day 1 and continous infusion 5-fluorouracil 750 mg/m"2 on day 1 to 5 and, subsequently, radiotherapy, with the delivery of a total dose of 46 Gy to the whole pelvis, with additional boost doses of 20 Gy to the prostatic bed and adjunctive 6 Gy to the prostate gland (72 Gy in total). The patient remained free of disease for 5 years, finally experiencing local relapse and, subsequently, dying of acute renal failure due to bilateral uretero-hydro-nephrosis. In addition, we provide a complete overview of all reported cases available within the medical literature. Since it remains questionable which should be the most appropriate therapeutic approach towards prostate pure squamous cell carcinoma, our report demonstrates that a prolonged disease control, with a consistent survival time, may be achieved by the combination of an effective local treatment such as radiotherapy with systemic infusion of chemotherapeutic drugs