Phase I/II study of oral etoposide plus GM-CSF as second-line chemotherapy in platinum-pretreated patients with advanced ovarian cancer

The aim of this phase I/II study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities of chronic oral etoposide given on days 1–10 followed by rescue with subcutaneous (s.c.) granulocyte-macrophage colony-stimulating factor (GM-CSF) on days 12–19 as second-line chemotherapy in platinum-pretreated patients (pts) with advanced ovarian carcinoma. Cohorts of three to six pts were treated with doses of oral etoposide from 750 mg m−2 cycle−1 escalated to 1250 mg m−2 cycle−1 over 10 days, every 3 weeks. Subcutanous GM-CSF, 400 μg once daily, days 12–19, was added if dose-limiting granulocytopenia was encountered. In total, 18 pts with a median Karnofsky index of 80% (range, 70–100%) and a median time elapsed since the last platinum dose of 10 months (range, 1–24 months), 30% of whom showed visceral metastases, were treated at four dose levels (DLs) of oral etoposide on days 1–10 of each cycle as follows: DL 1, 750 mg m−2 cycle−1, without GM-CSF, three pts; DL 2, 1000 mg m−2 cycle−1, without GM-CSF, three pts; DL 3, 1000 mg m−2 cycle−1, with GM-CSF, six pts; and DL 4, 1250 mg m−2 cycle−1, with GM-CSF, six pts. All pts were assessable for toxicity and 16 pts for response. Dose-limiting toxicity (DLT) was reached at DL 4 by three of six pts, showing World Health Organization (WHO) toxicity grade 4. One patient died from gram-negative sepsis associated with granulocytopenia grade 4. Two more pts developed uncomplicated granulocytopenia grade 4. Thus, we recommend that DL 3 can be used for further phase II evaluation (i.e. oral etoposide 1000 mg m−2 cycle−1, days 1–10, followed by s.c. GM-CSF 400 μg, days 12–19). The clinical complete or partial responses in each patient cohort were: DL 1, one of three pts; DL 2, one of three pts; DL 3, three of five pts; and DL 4, two of five pts. In conclusion, in this phase I/II study, we defined the MTD and the dose recommended for the therapy with oral etoposide given over 10 days followed by s.c. GM-CSF in platinum-pretreated patients with advanced ovarian cancer. Our data demonstrate encouraging activity of this regimen and strongly support its further investigation in a phase II study

Epidemiology of colorectal cancer in Belgium

En se référant à l'Institut National de Statistiques de Belgique, à l'annuaire statistique de la Santé Publique de Belgique, et aux Rapports de Statistiques Sanitaires Mondiales émis par l'O.M.S., les auteurs mettent en exergue, l'importance du problème posé par le cancer du gros intestin, deuxième cause de mortalité par néoplasme malin en Belgique. Les comparaisons entre sexes, groupes d'âges, groupes géographiques et évolution dans le temps sont abordées. On souligne le taux élevé du cancer colique, fait maintenant habituel dans les pays à mode de vie occidentale, contrastant avec l'évolution du cancer de l'estomac dont l'incidence a diminué d'environ 36 % pour la période de référence

Cell proliferation of pericryptal fibroblasts in the rat colon mucosa.

The turnover of pericryptal fibroblasts in the rat colon mucosa was analysed after in vivo incorporation of tritiated thymidine. Thirty-six rats were serially killed one hour to 21 days after intraperitoneal injection of the radionuclide. At one hour, the labelling index of pericryptal fibroblasts was only 2.44%; labelled fibroblasts were slightly predominant along the lower two-thirds of the crypts. Within 24 hours, most underwent at least one cell division. No migration was observed and a significant proportion of labelled fibroblasts was still present after three weeks. It is concluded that those fibroblasts constitute a slowly renewing cell population. The data failed to confirm the hypothesis of an 'en bloc' migration of fibroblasts in synchrony with the epithelial cells