Marketing authorization procedures for advanced cancer drugs: exploring the views of patients, oncologists, healthcare decision makers and citizens in France

International audienceBackground. The past decades have seen advances in cancer treatments in terms of toxicity and side effects but progress in the treatment of advanced cancer has been modest. New drugs have emerged improving progression free survival but with little impact on overall survival, raising questions about the criteria on which to base decisions to grant marketing authorizations and about the authorization procedure itself. For decisions to be fair, transparent and accountable, it is necessary to consider the views of those with relevant expertise and experience. Methods. We conducted a Q-study to explore the views of a range of stakeholders in France, involving: 54 patients (18 months after diagnosis); 50 members of the general population; 27 oncologists; 19 healthcare decision makers; and 2 individuals from the pharmaceutical industry. Results. Three viewpoints emerged, focussing on different dimensions entitled: 1) ‘Quality of life (QoL), opportunity cost and participative democracy’; 2)‘QoL and patient-centeredness’; and 3) ‘Length of life’. Respondents from all groups were associated with each viewpoint, except for healthcare decision makers, who were only associated with the first one. Conclusion. Our results highlight plurality in the views of stakeholders, emphasize the need for transparency in decision making processes, and illustrate the importance of a re-evaluation of treatments for all 3 viewpoints. In the context of advanced cancer, our results suggest that QoL should be more prominent amongst authorization criteria, as it is a concern for 2 of the 3 viewpoints

A long-term survivor of repeated inguinal nodes recurrence of papillary serous adenocarcinoma of CUP: case report

BACKGROUND: Tumor spread beyond the peritoneal cavity in cases of papillary serous adenocarcinoma of the unknown primary (CUP) is a rare late event and carries a poor prognosis. CASE PRESENTATION: A 71-year-old female was referred to our hospital because of a large right inguinal tumor with biopsy evidence of carcinoma as well as an elevated serum CA125 (cancer antigen 125). She underwent complete resection of the right inguinal tumor and multiple pelvic tumors, which involved the rectum, ovary and uterus. Pathological examination revealed the tumors to be metastases of a papillary serous adenocarcinoma with a psammoma body of CUP. On the 28th postoperative day, newly developed asymptomatic small left inguinal node metastases in the setting of a normal CA125 level were removed. Four and a half years after the primary resection, the CA125 level increased again and newly developed asymptomatic metastases were found in the right deep inguinal nodes and extirpated at that time. All surgical resections followed the modified FAM (5FU, Adriamycin; ADM, MMC) regimen, including protracted dairy oral administration of UFT or 5'-FDUR, Cimetidine and PSK (protein-bound polysaccharide K) as an immunomodulator or biological response modifier in conjunction with intermittent one-day continuous infusion (ADM+MMC) or intermittent single bolus injection of ADM+MMC. At present, the patient has been living in good health for almost 7 years with no evidence of relapse. CONCLUSION: Aggressive resection surgery followed by effective adjuvant chemotherapy is necessary for surviving long time without relapse of poorly prognostic patients with metastases outside of the abdominal cavity from peritoneal papillary serous adenocarcinomas

Diagnosis and management of anaemia and iron deficiency in patients with haematological malignancies or solid tumours in France in 2009-2010: the AnemOnHe study

OBJECTIVE: To describe the management of anaemia in 2009-2010 in France in patients with haematological malignancies (HM) or solid tumours (ST). METHODS: Retrospective observational study in 57 centres, enrolling adult patients with HM or ST treated for an episode of anaemia (duration of the episode >/= 3 months occurring in the last 12 months). RESULTS: 220 patients with ST (breast, 18%; lung, 18%) and 56 with HM (lymphoma, 60%) were included (median age, 68 years; female, 53%). Mean haemoglobin level at anaemia diagnosis was 9.3 +/- 1.4 g/dL (<8 g/dL for 16%) and 9.8 +/- 1.1g/dL (<8 g/dL for 6%) in HM and ST patients, respectively. At least one parameter of iron deficiency (ferritin, transferrin saturation) was assessed in 26% of HM and 19% of ST patients. Treatment of anaemia included erythropoiesis-stimulating agents (ESA) for 98% of HM and 89% of ST patients. Iron was prescribed to 14% (oral, 12%; intravenous, 2%) of HM patients and to 42% (oral, 17%; intravenous, 25%) of ST patients. The rates of blood transfusions were high: 70% in HM and 46% in ST patients; transfusions alone or administrated with ESA were more frequent in patients with Hb <8 g/dL. CONCLUSION: Although recent guidelines recommend evaluating iron deficiency and correcting anaemia by using intravenous iron, our study in cancer patients evidenced that ESA and blood transfusions are still frequently used as the treatment of anaemia in cancer patients. Iron deficiency is insufficiently assessed (only one patient among five) and as a consequence iron deficiency is most likely insufficiently treated

Prognostic factors for tumour response, progression-free survival and toxicity in metastatic colorectal cancer patients given irinotecan (CPT-11) as second-line chemotherapy after 5FU failure

Our purpose was to determine, in patients with metastatic colorectal carcinoma treated with irinotecan single-agent after 5-FU failure, the most significant predictive parameters for tumour response, progression-free survival and toxicity. Between October 1992 and April 1995, 455 patients with 5-FU resistant metastatic colorectal carcinoma entered four consecutive phase II trials. The first two studies assessed tumour response, the other two were randomized studies which assessed the efficacy of racecadotril to prevent irinotecan-induced diarrhoea. Due to homogeneous main eligibility criterias, data from those studies could be pooled for statistical analysis. Potential clinical and biological predictive factors (PF) for toxicity, tumour growth control, e.g. response or stabilization and progression-free survival (PFS), were studied in multivariate analysis. 363 patients were evaluable for response, 432 were evaluable for PFS, 368 for neutropenia and 416 for delayed diarrhoea, respectively. Normal baseline haemoglobin level (Hb), time since diagnosis of colorectal carcinoma, grade 3 or 4 neutropenia or diarrhoea at first cycle and a low number of organs involved were the most PF for tumour growth control (P< 0.05). Significant prognostic variables for PFS were WHO Performance Status, liver and lymph-node involvement, time since diagnosis, age and CEA value (P≤ 0.02). Six groups of patients based on the number of unfavourable prognostic factors are presented. Baseline bilirubin, haemoglobin level, number of organs involved and time from diagnosis were PF for neutropenia; PS, serum creatinine, leukocyte count, time from 5-FU progression and prior abdominopelvic irradiation were PF for delayed diarrhoea (P≤ 0.05). These PF should help clinicians to anticipate for a given patient the probability to observe a response/stabilization or a toxicity. These results should also be prospectively confirmed in ongoing or future trials using irinotecan, both as a single agent and in combination with other drugs. © 2000 Cancer Research Campaig

Quality of life of palliative chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction treated with irinotecan combined with 5-fluorouracil and folinic acid: results of a randomised phase III trial

41st Annual Meeting of the American-Society-of-Clinical-Oncology -- MAY 13-17, 2005 -- Orlando, FLWOS: 000268881000007PubMed ID: 19568958The quality of life (QL) of advanced gastric cancer patients receiving irinotecan, folinic acid and 5-fluorouracil (5-FU) (IF arm) or cisplatin with 5-FU (CF arm) is presented. Patients with measurable or evaluable advanced gastric cancer received IF weekly for 6/7 weeks or CF q4 weeks. QL was assessed using the EORTC QLQ-C30 at baseline, subsequently every 8 weeks until progression and thereafter every 3 months until death. The QL data were analysed using several statistical methods including summary measures and pattern-mixture modelling. A total of 333 patients were randomised and treated (IF 170, CF 163). The time-to-progression for IF and CF was 5.0 and 4.2 months (P = 0.088), respectively. The overall compliance rates for QL questionnaire completion were 60 and 56% in the IF and CF arms, respectively. Significant treatment differences were observed for the physical functioning scale (P = 0.024), nausea\vomiting (P = 0.001) and EQ-5D thermometer (P = 0.020) in favour of the IF treatment arm. There was a trend in favour of IF over CF in time-to-progression. The IF group also demonstrated a better safety profile than CF and a better QL on a number of multi-item scales, suggesting that IF offers an alternative first-line platinum-free treatment option for advanced gastric cancer.Amer Soc Clin Onco

Development and Validation of a Bedside Score to Predict Early Death in Cancer of Unknown Primary Patients

BACKGROUND: We have investigated predictors of 90-day-mortality in a large cohort of non-specific cancer of unknown primary patients. METHODS: Predictors have been identified by univariate and then logistic regression analysis in a single-center cohort comprising 429 patients (development cohort). We identified four predictors that produced a predictive score that has been applied to an independent multi-institutional cohort of 409 patients (validation cohort). The score was the sum of predictors for each patient (0 to 4). RESULTS: The 90-day-mortality-rate was 33 and 26% in both cohorts. Multivariate analysis has identified 4 predictors for 90-day-mortality: performance status>1 (OR = 3.03, p = 0.001), at least one co-morbidity requiring treatment (OR = 2.68, p = 0.004), LDH>1.5 x the upper limit of normal (OR = 2.88, p = 0.007) and low albumin or protein levels (OR = 3.05, p = 0.007). In the development cohort, 90-day-mortality-rates were 12.5%, 32% and 64% when the score was [0-1], 2 and [3]-[4], respectively. In the validation cohort, risks were 13%, 25% and 62% according to the same score values. CONCLUSIONS: We have validated a score that is easily calculated at the beside that estimates the 90-days mortality rate in non-specific CUP patients. This could be helpful to identify patients who would be better served with palliative care rather than aggressive chemotherapy