PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

[Superficial cancer of the stomach: evolution of their characteristics over a 20 year period in one population]. / Les cancers superficiels de l'estomac: évolution de leurs caractéristiques sur une période de 20 ans dans une population.

OBJECTIVES: The aim of this study was to analyse the incidence, treatment and prognosis of early gastric cancer in a population-based series and to draw a picture of time trends. METHODS: Over a 20-year period (1976-1995), 80 early gastric cancers were diagnosed in the Côte-d'Or area (493,000 residents). Incidence rates were calculated by sex, age groups and 5-year periods. Prognostic factors were determined using the Kaplan-Meier method and the Cox model. RESULTS: Age-standardized incidence rates were 0.8/100,000 in men and 0.3/100,000 in women. Incidence increased slightly over time (NS) and their proportion among gastric cancers increased from 3.4% (1976-1980) to 7.9% (1991-1995) (P < 0.01). Among these cancers, 25 were intramucosal (31.3%), 55 were submucosal (68.8%) and 8 had lymph node metastases (10.0%). Overall 21 patients (24.1%) had already been treated for a peptic ulcer. The 5-year crude survival rate was 63.1% and the corresponding net survival rate was 86.3%. Lymph node metastases, location, sex and cancer extension and age were independent prognostic factors. CONCLUSIONS: Though it is on the increase, the proportion of early gastric cancers remains low among gastric cancers. This study confirms the importance of performing a gastroscopy with biopsy upon each bout of ulcer and that the prognosis is lower than suggested by hospital based series.

[Adjuvant chemotherapy for colon adenocarcinoma in the county of Côte-d'Or]. / Chimiothérapie adjuvante pour adénocarcinome colique dans le département de la Côte-d'Or.

OBJECTIVES: The aim of this study was to assess the use of adjuvant chemotherapy in colon adenocarcinomas on a population basis and determine which factors could modulate its prescription. METHODS: The influence of time of diagnosis, age, sex, place of residence, health care pattern, tumor location and number of metastatic lymph nodes was investigated from the 1988 to 1995 data from the Registry of Digestive Cancers in Côte-d'Or (France). Each independent variable was given an odds-ratio (OR). RESULTS: An adjuvant chemotherapy was performed for 0.9% of 231 Dukes'A cancers, 3.8% of 367 Dukes'B and 16.7% of 264 Dukes'C. For the latter, the prescription of adjuvant chemotherapy was influenced by time of diagnosis (from 1.3% in 1988-89 to 35.8% in 1994-95; OR = 228 for period 1994-95 compared with the first period), age (the proportion of treated patients under 75 years of age has increased from 2.2% in 1988-89 to 57.9% in 1994-95; OR = 30.1 for patients younger than 75 years compared with older ones) and health care pattern (OR = 0.21 for treatment in non university hospitals and 0.06 in the private sector compared with university hospitals. CONCLUSION: In spite of an increasing proportion of patients treated by adjuvant chemotherapy for Dukes'C colon cancers, this treatment of proved effectiveness has not yet reached its full development.

Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin.

BACKGROUND: The combination of 5-fluorouracil (5-FU) and cisplatin has shown great activity in many different types of tumour with an in vitro synergistic effect between 5-FU and cisplatin. A phase II study of 5-FU plus cisplatin was performed in 25 previously untreated patients with inoperable locally advanced or metastatic biliary tract carcinoma. PATIENTS AND METHODS: Twenty-five patients, 10 of them men and 15 women with a median age of 58, were entered into the study. The chemotherapy regimen consisted of 5-FU: 1 g/m2/day in continuous intravenous (i.v.) infusion for five consecutive days, and cisplatin: 100 mg/m2/day on day 2 in a one-hour infusion with standard hyperhydration. Twenty-two patients had metastatic tumours and three had locally advanced disease. RESULTS: Of the 25 patients entered into the study, 24 were evaluable for response and 25 for toxicity. Nausea and vomiting was the main toxic side effect in 19 patients. Severe, WHO grade 3-4 thrombocytopenia or neutropenia were observed in three and seven patients, respectively. There were no toxic deaths. Of 25 patients, six had partial remissions (overall response 24%, 95% confidence interval 7%-41%). For three patients, tumour reduction permitted local radiotherapy and one of these patients with initially advanced disease is still alive six years after the beginning of treatment. CONCLUSIONS: This study, one of the largest phase II trials performed in this disease, shows interesting activity of the combination of 5-FU and cisplatin in advanced biliary tract carcinoma.

Time trends in diagnostic strategy, treatment, and prognosis of gastric cancer in the elderly: a population based study.

The impact of changes in diagnostic strategies for gastric cancer and attitudes towards surgery in elderly patients is not known. A population-based series of 842 gastric cancers diagnosed between 1976 and 1993 in patients aged 70 and older in Côte-dOr, France, was used to establish trends in diagnostic strategy, treatment, and prognosis. The use of endoscopy alone increased from 3% (1976-78) to 81% (1991-93). This trend was initially associated with a decrease in the use of x-ray alone, then with a decrease in the use of both x-ray and endoscopy. The proportion of resection for cure increased from 26% during 1976-78 to 43% during 1991-93 (P < 0.001). The proportion of cancers not extending beyond the gastric wall increased from 12% to 24% (P < 0.05). Operative mortality decreased from 38.7% (1976-78) to 13.3% (1991-93) and the corresponding 3-year crude survival rate rose from 7% to 18%. Improvements in the care of gastric cancer in elderly patients have been achieved, but further progress is warranted.

[Fight against cancer of the exocrine pancreas: stagnation or progress? The point of view of the Fondation française de cancérologie digestive (FFCD)]. / Lutte contre le cancer du pancréas exocrine: stagnation ou progrès? Le point de vue de la Fondation française de cancérologie digestive (FFCD).

This paper updates recent trends concerning ductal pancreatic cancer. Knowledge of the cellular mechanisms has improved, and new developments in imaging allow a more accurate staging. Although operative mortality sharply decreased during these last 15 years, the prognosis of pancreatic carcinoma remains dismal, due to late diagnosis, as only one out of ten patients is considered for curative resection. Therapeutic research groups, and among them the Fondation française de cancérologie digestive (FFCD), do their best to develop new therapeutic strategies, including post-operative or preferentially pre-operative radio-chemotherapeutic adjuvant treatments, and to improve chemotherapy in metastatic cancers.

[Treatment of cancer of the rectum. Practical survey based on 7 French departments in 1990]. / Traitement du cancer du rectum. Enquête de pratique dans 7 départements français en 1990.

OBJECTIVES AND METHODS: Therapeutic modalities in rectal cancer were analyzed in a French population based study. This work reviewed all the new cases of rectal adenocarcinoma diagnosed in a one-year period from January 1st to December 31st 1990 among the population of 7 provinces. Thus, 427 new cases of rectal cancer were included in a data base (EUROCARE). The main goal of this study was to provide an up-to-date, unbiased evaluation of the different treatments of rectal cancer according to its stage when diagnosed. The aim was also to point out differences in therapeutic management between these different geographic areas. A three-stage clinico-pathological staging was used to minimize stage migration bias. RESULTS: 77.8% of the patients underwent a rectal excision; among them, 53.9% had a sphincter saving procedure. Adjuvant radiotherapy was associated to rectal resection in 46.2% of the patients and was pre-operative in 45.9%. Only 13.7% of patients had chemotherapy. CONCLUSIONS: We demonstrated a significative difference of therapeutic modalities between these different french geographic areas concerning adjuvant radiotherapy and chemotherapy. This work supports the need and the value of population-based study for clinical management, prognostic evaluation and evaluation of public health issues.