Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial.

BACKGROUND: Fluorouracil-based chemoradiotherapy is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine. METHODS: This randomised, open-label, multicentre, non-inferiority, phase 3 trial began in March, 2002, as an adjuvant trial comparing capecitabine-based chemoradiotherapy with fluorouracil-based chemoradiotherapy, in patients aged 18 years or older with pathological stage II-III locally advanced rectal cancer from 35 German institutions. Patients in the capecitabine group were scheduled to receive two cycles of capecitabine (2500 mg/m(2) days 1-14, repeated day 22), followed by chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) days 1-38), then three cycles of capecitabine. Patients in the fluorouracil group received two cycles of bolus fluorouracil (500 mg/m(2) days 1-5, repeated day 29), followed by chemoradiotherapy (50·4 Gy plus infusional fluorouracil 225 mg/m(2) daily), then two cycles of bolus fluorouracil. The protocol was amended in March, 2005, to allow a neoadjuvant cohort in which patients in the capecitabine group received chemoradiotherapy (50·4 Gy plus capecitabine 1650 mg/m(2) daily) followed by radical surgery and five cycles of capecitabine (2500 mg/m(2) per day for 14 days) and patients in the fluorouracil group received chemoradiotherapy (50·4 Gy plus infusional fluorouracil 1000 mg/m(2) days 1-5 and 29-33) followed by radical surgery and four cycles of bolus fluorouracil (500 mg/m(2) for 5 days). Patients were randomly assigned to treatment group in a 1:1 ratio using permuted blocks, with stratification by centre and tumour stage. The primary endpoint was overall survival; analyses were done based on all patients with post-randomisation data. Non-inferiority of capecitabine in terms of 5-year overall survival was tested with a 12·5% margin. This trial is registered with ClinicalTrials.gov, number NCT01500993. FINDINGS: Between March, 2002, and December, 2007, 401 patients were randomly allocated; 392 patients were evaluable (197 in the capecitabine group, 195 in the fluorouracil group), with a median follow-up of 52 months (IQR 41-72). 5-year overall survival in the capecitabine group was non-inferior to that in the fluorouracil group (76% [95% CI 67-82] vs 67% [58-74]; p=0·0004; post-hoc test for superiority p=0·05). 3-year disease-free survival was 75% (95% CI 68-81) in the capecitabine group and 67% (59-73) in the fluorouracil group (p=0·07). Similar numbers of patients had local recurrences in each group (12 [6%] in the capecitabine group vs 14 [7%] in the fluorouracil group, p=0·67), but fewer patients developed distant metastases in the capecitabine group (37 [19%] vs 54 [28%]; p=0·04). Diarrhoea was the most common adverse event in both groups (any grade: 104 [53%] patients in the capecitabine group vs 85 [44%] in the fluorouracil group; grade 3-4: 17 [9%] vs four [2%]). Patients in the capecitabine group had more hand-foot skin reactions (62 [31%] any grade, four [2%] grade 3-4 vs three [2%] any grade, no grade 3-4), fatigue (55 [28%] any grade, no grade 3-4 vs 29 [15%], two [1%] grade 3-4), and proctitis (31 [16%] any grade, one [<1%] grade 3-4 vs ten [5%], one [<1%] grade 3-4) than did those in the fluorouracil group, whereas leucopenia was more frequent with fluorouracil than with capecitabine (68 [35%] any grade, 16 [8%] grade 3-4 vs 50 [25%] any grade, three [2%] grade 3-4). INTERPRETATION: Capecitabine could replace fluorouracil in adjuvant or neoadjuvant chemoradiotherapy regimens for patients with locally advanced rectal cancer. FUNDING: Roche Pharma AG (Grenzach-Wyhlen, Germany).

Anatomy of subterranean organs of medicinally used cardueae and related species and its value for discrimination.

Numerous species of the Asteraceae, the composites, are famous for their use in both traditional and conventional medicine. Reliable anatomical descriptions of these plants and of possible adulterations provide a basis for fast identification and cheap purity controls of respective medicinal drugs by means of light microscopy. Nevertheless, detailed comparative studies on root and rhizome anatomy of valuable as well as related inconsiderable composite plants are largely missing yet. The presented study aims to narrow this gap by performing anatomical analyses of roots and rhizomes of 16 species belonging to the tribe Cardueae, of formerly and currently used drugs as well as their near relatives as potential adulterations (Carlina acaulis L., Carlina vulgaris L., Arctium lappa L., Arctium tomentosum Mill., Carduus defloratus L., Carduus personata (L.) Jacq, Cirsium arvense (L.) Scop., Cirsium vulgare (Savi) Ten., Cirsium erisithales (Jacq.) Scop., Onopordum acanthium L., Silybum marianum (L.) Gaertn., Rhaponticum scariosum Lam., Centaurea jacea L., Centaurea scabiosa L., Centaurea cyanus L., Cnicus benedictus L.). A detailed verbal and graphical survey of the analysed anatomical features is provided. Several characters were finally extracted which allow for discrimination of the examined species and may be effectively used for drug quality controls.

Microscopical discrimination of the subterranean organs of medicinally used plants of the Cichorieae and their relatives.

CONTEXT: Light microscopy is in most cases a quick method for the identification and discrimination of medicinally used plant drugs; moreover, this technique is very inexpensive. Reliable descriptions of the anatomy of plants and their adulterations are prerequisites for necessary purity controls. OBJECTIVE: The anatomy of the subterranean organs of 18 pharmaceutically useful as well as related but inconsiderable Asteraceae species from nine genera (Taraxacum F. H. Wigg., Leontodon L., Scorzoneroides Moench, Hypochaeris L., Crepis L., Aposeris Neck., Cichorium L., Scorzonera L., and Tragopogon L.; tribe Cichorieae, Asteraceae) is described in detail and graphically illustrated. Features characterizing and discriminating the studied taxa are presented and discussed. MATERIALS AND METHODS: The roots/rhizomes of various species were examined by means of light microscopy. RESULTS: Useful anatomical characters were found for the discrimination between the species, and some of them were examined for the first time. DISCUSSION AND CONCLUSION: Discrimination of most genera and species investigated was possibly based on the anatomy of their underground parts. The identified characters may be effectively used for quality control of commercial drugs and the identification of adulterations.

Traditional medicine in the pristine village of ProkoÅko Lake on Vranica Mountain, Bosnia and Herzegovina.

The results of an ethnobotanical study conducted in the pristine village of ProkoÅko Lake (Vranica Mountain, Bosnia and Herzegovina) in summer 2007 is presented. Informal interviews involving 12 informants known as âtraditional healersâ provided data from 43 plants used in 82 prescriptions. The applied plants were used for a broad spectrum of indications. The most frequent were gastro-intestinal tract ailments, blood system disorders, skin ailments, respiratory tract ailments and urinary-genital tract ailments. The most frequent preparation was an infusion. Other often used preparations were ointments or balms and decocts. The special Bosnian balms known as âmehlemsâ were prepared from freshly chopped or freshly pressed herbal parts of various plant species. Warmed resins from Abies or Picea species, raw cow or pig lard, olive oil and honey served as basis. The traditional doctors, who usually worked as a team, enjoyed such a good reputation that people from all over the country were visiting in search of alternative ways to cure their ailments and diseases. The practical techniques applied by the healers and some of their attitudes and values are reported.