How to measure the net benefit of treatment?

Estimating net benefit makes possible to clarify the basis for therapeutic decisions on an individual and collective level. This clarification is a must in shared medical decision-making and evidence-based medicine. Numerous methods are available, although none outweigh the others.

Postoperative irinotecan in resected stage II-III rectal cancer: final analysis of the French R98 Intergroup trial†.

Backgroud: The R98 trial explores the addition of irinotecan to a 5-fluorouracil (5-FU) plus leucovorin (5-FU/LV) adjuvant regimen in optimally resected stages II-III rectal cancers. We report the updated long-term results. Disease-free survival (DFS) was the primary end point.

A phase III adjuvant randomised trial of 6 cycles of 5-fluorouracil-epirubicine-cyclophosphamide (FEC100) versus 4 FEC 100 followed by 4 Taxol (FEC-T) in node positive breast cancer patients (Trial B2000).

Background: Standard adjuvant chemotherapy regimens for patients with node positive (N+) breast cancer consisted of anthracycline followed by taxane. The European Association for Research in Oncology embarked in 2000 on a phase III trial comparing 6 cycles of FEC100 versus 4 FEC100 followed by 4 Taxol. Primary end-point was disease free survival.

[Criteria and endpoints in advanced prostate cancer].

In castrate-refractory prostate cancers, main efficacy endpoints are progression free survival for phase-II trials and overall survival for phase-III trials. However, various progression criteria have been used, and overall survival may become more difficult to impact due to the recent approval of more effective drugs. PSA is useful in clinical practice, provided it is interpreted with caution, but cannot be used as a surrogate endpoint in clinical trials.

[Phyllodes tumors and breast sarcomas: a review].

Phyllodes tumors and sarcomas of the breast are non-epithelial tumors of the breast. Phyllodes tumors are benign tumors, tumors of intermediate malignancy or malignant tumors. The differential diagnosis with a very proliferant fibroadenoma may be difficult.

[Meta-analysis based on individual patient data: example of advanced colorectal cancer].

The authors mention the existing methods to perform meta-analysis, and show that meta-analysis based on individual patient data (IPD meta-analyses) are the most reliable. Taking the example of 4 successive meta-analysis of clinical trials in advanced colorectal cancer, they illustrate the possibilities of IPD meta-analysis. They conclude that meta-analysis are a powerful tool not only to confirm small differences between treatment modalities, but also to generate hypothesis, to perform exploratory subgroup analysis, and to study potential surrogate endpoints.

[Management of biliary tract carcinomas].

Biliary tract carcinomas are rare tumours, counting for less than 5% of cancer. Biliary tract carcinomas comprise gallbladder carcinoma and cholangiocarcinoma, which arise from the intrahepatic or extrahepatic bile ducts. These tumours have a poor prognosis, with a median survival of 6 months for advanced disease.

[Fulvestrant use in clinical practice in France: a pharmacoepidemiologic study].

The objective of the study was to assess the prescription patterns of fulvestrant in clinical practice in France through a retrospective observational study. Primary endpoint was treatment duration. Data from patients who completed fulvestrant therapy between January and May 2007 were collected between May and June 2007 in 50 centers selected among a representative study sample of 110 centers.

Chemotherapy has also an effect on primary tumor in colon carcinoma.

Background: This study characterizes the histological effect of chemotherapy (CT) on primary colonic tumors.

Methods: Between 2000 and 2006, 38 patients with stage IV colon cancer underwent resection of the primary, after chemotherapy (CT group, n = 16) or without preoperative CT (control group, n = 22). For all primary tumors, histological analysis included: fibrosis, acellular necrosis, acellular mucin pools, lymphoplasmacytic infiltration, and changes at tumor surface.

Fixed-dose rate gemcitabine in elderly patients with advanced pancreatic cancer: an observational study.

Pancreatic cancer represents one of the most lethal cancers and treatment of advanced disease remains palliative. Age-related physiologic changes can increase chemotherapy's toxicity but the use of gemcitabine in elderly patients has not been properly evaluated. This observational prospective study evaluated patients aged 70 years and over, receiving gemcitabine for an advanced pancreatic carcinoma.

Endpoints and surrogate endpoints in colorectal cancer: a review of recent developments.

Purpose Of Review: The purpose of this review is to discuss recently published work on endpoints for early and advanced colorectal cancer, as well as the statistical approaches used to validate surrogate endpoints.

Recent Findings: Most attempts to validate surrogate endpoints have estimated the correlation between the surrogate and the true endpoint, and between the treatment effects on these endpoints. The correlation approach has made it possible to validate disease-free survival and progression-free survival as acceptable surrogates for overall survival in early and advanced disease, respectively.

Surrogate endpoints for overall survival in advanced colorectal cancer: a clinician's perspective.

Surrogate endpoints in oncology research and practice have garnered increasing attention over the past two decades. This activity has largely been driven by the promise surrogate endpoints appear to hold: the potential to get new therapies to seriously ill patients more rapidly. However, uncertainties abound.

[Randomised phase II trials in oncology].

The purpose of phase II trials is to identify signals in favor of the efficacy of a drug in development. The main pitfall of a phase II study is to conclude by error that a drug has no activity, leading to a stop in the development of a drug which has a real efficacy. In oncology, more and more phase II trials are randomised, even though there are still numerous non randomised studies.

Progression-free survival is a surrogate for survival in advanced colorectal cancer.

Purpose: The traditional end point for assessing efficacy of first-line chemotherapies for advanced cancer is overall survival (OS), but this end point requires prolonged follow-up and is potentially confounded by the effects of second-line therapies. We investigated whether progression-free survival (PFS) could be considered a valid surrogate for OS in advanced colorectal cancer.

Patients And Methods: Individual patient data were available from 10 historical trials comparing fluouracil (FU) + leucovorin with either FU alone (1,744 patients) or with raltitrexed (1,345 patients) and from three validation trials comparing FU + leucovorin with or without irinotecan or oxaliplatin (1,263 patients).

Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1.

Purpose: This randomized, 2 x 2 factorial study compared a semimonthly regimen (fluorouracil [FU] and leucovorin [LV] semi-monthly is LV5FU2) with a monthly regimen of FU and LV (mFU/LV) as well as 24 weeks versus 36 weeks of each regimen as adjuvant treatment of stage II and III colon cancer.

Patients And Methods: LV5FU2 was administered semimonthly for 2 days as racemate (dl) or levogyre (l-; 200 or 100 mg/m(2)) as a 2-hour infusion, followed by 400 mg/m(2) FU bolus and a 600-mg/m(2) FU 22-hour continuous infusion. FU and LV were administered monthly (mFU/LV) for 5 days as dl- or l-LV 15-minute infusion, followed by a 400 mg/m(2) FU 15-minute infusion.

Stents for palliation of obstructive metastatic colon cancer: impact on management and chemotherapy administration.

Hypothesis: The more rapid and less complicated recovery after palliative stent insertion compared with surgery may theoretically facilitate the early administration of chemotherapy.

Design: A retrospective study.

Setting: University tertiary care referral center.

Phase II study of UFT with leucovorin and irinotecan (TEGAFIRI): first-line therapy for metastatic colorectal cancer.

This phase II trial was performed to evaluate the efficacy and tolerability of oral tegafur-uracil (UFT) with leucovorin (LV) combined with intravenous (i.v.) irinotecan every 3 weeks (TEGAFIRI) as first-line treatment for patients with metastatic colorectal cancer (mCRC).

A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer.

Background: Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer.

Methods: A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries.

Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial.

Purpose: Complete resection of liver metastases of colorectal origin is the only potentially curative treatment. In order to decrease recurrences, the use of adjuvant systemic chemotherapy after liver resection is controversial because no randomized study demonstrated its benefit.

Patients And Methods: In a multicenter trial, we randomly assigned 173 patients with completely resected (R0) hepatic metastases from colorectal cancer to surgery alone and observation (87 patients) or to surgery followed by 6 months of systemic adjuvant chemotherapy with a fluorouracil and folinic acid monthly regimen (86 patients).

Impact of on-site initiation visits on patient recruitment and data quality in a randomized trial of adjuvant chemotherapy for breast cancer.

Purpose: To provide empirical evidence on the impact of on-site initiation visits on the following outcomes: patient recruitment, quantity and quality of data submitted to the trial coordinating office, and patients' follow-up time.

Patients And Methods: This methodological study was performed as part of a randomized trial comparing two combination chemotherapies for adjuvant treatment of breast cancer. Centers participating to the trial were randomized to either receive systematic on-site visits (Visited group), or not (Non-visited group).

Dose-dense adjuvant chemotherapy in node-positive breast cancer: docetaxel followed by epirubicin/cyclophosphamide (T/EC), or the reverse sequence (EC/T), every 2 weeks, versus docetaxel, epirubicin and cyclophosphamide (TEC) every 3 weeks. AERO B03 randomized phase II study.

Background: Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive patients but optimal dose and schedule remain undetermined. This study aimed to select a dose-dense regimen for further assessment in phase III studies.

Patients And Methods: Ninety-nine patients with node-positive invasive breast adenocarcinoma were randomly assigned to docetaxel (Taxotere) (T) 75 mg/m2, epirubicin (E) 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 (TEC)x6, every 3 weeks; E 100 mg/m2, C 600 mg/m2 x 4, then T 100 mg/m2 x 4 (EC-->T) or the reverse sequence (T-->EC), every 2 weeks, with pegfilgrastim support.

Adenocarcinomas of unknown primary (ACUP) of the mediastinum mimicking lymphoma: CT findings at diagnosis and follow-up.

Objective: To describe the computed tomography (CT) features at diagnosis and after treatment of adenocarcinoma of unknown primary (ACUP) mimicking lymphoma of the mediastinum.

Methods: Fifteen patients with pathologically proven ACUP and with primarily mediastinal involvement were initially referred to the Hematologic Department of our institution with a suspected diagnosis of lymphoma, and accounted for our study population. Presenting symptoms and baseline biological values were analyzed.

Progresses in the medical treatment of advanced colorectal cancer.

In the last 2 decades, major progresses have been made in the management of patients with advanced colorectal cancer (ACC). The modulation of 5-fluorouracil (5-FU) by folinic acid (LV), followed by the introduction of irinotecan and oxaliplatin have significantly improved the outcome of these patients. New strategies consist of oral fluoropyrimidines, and of targeted agents to inhibit cancer signalisation.