High-dose intravenously (i.v) vitamin C in cancer patients is controversial. Numerous studies carried out on cancer cell lines and animal models demonstrated that millimolar vitamin C concentrations inhibit tumor cells viability, especially in association with chemotherapy. In cancer patients, high-dose i.v vitamin C in monotherapy does not show any anti-cancer activity. Clinical trials assessing high-dose i.v vitamin C concomitantly with chemotherapy do not conclude to reliable evidence for tumor control or overall survival benefit. Randomized double-blind trials are warranted.

To evaluate and compare the efficacy of subconjunctival bevacizumab injections alone, photodynamic therapy alone and combined treatments for reduction of corneal neovascularization.

The international phase IIIb study, ATHENA assessed the combination of bevacizumab/taxane-based chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer (mBC) in real-life setting. Among the 365 patients included in France, median overall survival (OS) is 28.4 months (CI95% 24.8-33.0), with a median time from treatment start to end of study of 36,5 months (25,1-45,4). Exploratory analyses in three sub-groups show that the median OS in long responder patients (not progressing for at least one year; n = 116) is not reached. In responder patients (n = 308), median OS is 33.0 months (CI95% 28.6-37.4) and 12.4 months (CI95% 11.2-17.4) in non-responders (n = 41). In patients with mBC expressing hormone receptors (HR+), treated with first-line hormone therapy before inclusion (n = 87) median OS in is 23.2 months (CI95% 19.6-28.6), and 35.3 months (CI95% 32.2-not reached); P = 0.004 in patients treated first with chemotherapy + bevacizumab (n = 179). The safety analysis in the various sub-groups of grade 3-5 adverse events of particular interest to bevacizumab of this study was comparable to the safety data of randomized phase III studies.

To compare chemoradiation with systemic chemotherapy to chemotherapy alone in locally advanced pancreatic cancer.

There is no standard second-line treatment for small cell lung cancer (SCLC). The prognosis of these patients is poor and special attention should be paid to both quality of life and economic factors.

In 1996, a multicenter randomized study comparing after breast-conservative surgery, sequential vs concurrent adjuvant chemotherapy (CT) with radiation therapy (RT) was initiated (ARCOSEIN study). Seven hundred sixteen patients were included in this trial. After a median follow-up of 6.7 (4.3-9) years, we decided to prospectively evaluate the late effects of these two strategies.

In breast cancer, radiation therapy improves local control rate and survival. When chemotherapy and radiation are indicated the sequencing of the two treatments is still controversial. Several studies have suggested that adjuvant radiotherapy could be safely delayed until adjuvant chemotherapy was completed. Other studies, most of them retrospective, pointed out that a delay in the initiation of radiotherapy to give chemotherapy first, will result in a increased rate of local recurrence. Concomitant administration of the two treatments is an alternative. Pilot studies have suggested the feasibility of simultaneous administration using selected regimen as CMF or FNC. A randomized phase III trials has been conducted to compare sequential treatment with chemotherapy first and radiation versus concomitant treatments. Preliminary results of this study are presented.

Ovarian cancer is the most frequent cause of death due to gynecologic malignancy in both the United States and in Europe. A phase III investigation compared second line treatment Caelyx with topotecan in patients with advanced epithelial ovarian carcinoma who failed a first-line platinum-containing regimen. A total of 474 patients were enrolled Although no significant advantage of Caelyx over topotecan with regards to overall survival and progression was found, there were fewer adverse events in the Caelyx arm and Caelyx had significantly better quality of life profile. We conducted a cost minimization analysis of both treatment arms. Costs were estimated from the viewpoint of the hospital, over the duration of the study period (12 weeks). The frequency of adverse events was derived from the trial's CRF, the treatment patterns of adverse events was estimated for each type of adverse event and each grade for a given type of adverse event. Costs included that of the drug and management of adverse events. Because of uncertainty on actual time spent in French hospitals, administration costs were not valued. Adverse events valued in the analysis were: stomatitis/ pharyngitis, PPE, nausea/vomiting diarrhea, anemia, thrombocytopenia, neutropenia, sepsis, fever. Drug costs and costs of blood products were valued using the purchase price by the hospital, costs of tests and hospital days were estimated from the hospital's accounting system. The drug cost per patient was 8,735 euros for Caelyx and 6,196 euros for topotecan, the cost of adverse events were 528 and 3,632 euros for Caelyx and topotecan respectively, due to the high rate of adverse events in patient treated with topotecan. The total costs were 9,279 and 9,938 for Caefyx and topotecan respectively.

To determine the efficacy and safety of bicalutamide, at the dose of 150 mg per day, as first-line monotherapy or as curative adjuvant therapy in patients with non-metastatic prostate cancer, and to investigate the possibility of a greater benefit for certain patient subgroups.

The main objective of this prospective multicenter randomised phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation versus fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma brain metastases.

This is a retrospective study of laryngeal preservation in endolaryngeal cancer with induction chemotherapy and radiotherapy for good responders. Between 1985 and 1995, 104 patients were treated in Institut Gustave Roussy (87 patients) and in Limoges (17 patients). The overall survival for the whole population was 76% and 69% at 3 and 5 years respectively, with a 36% rate of laryngeal preservation. In this retrospective series of patients, the single prognostic factor affecting survival was arytenoid mobility before treatment (66% and 55% at 3 years vs 85% and 82% at 5 years; p<0.004). Loco-regional failures were higher (33% vs 15%, p<0.03), and laryngeal preservation was lower (18% vs 51%) among patients with a fixed arytenoid (49 pts), compared with patients with a non fixed arytenoid (55 pts) ). The percentages of patients with a fixed arytenoid could explain the conflicting results of the two randomized studies of laryngeal preservation in laryngeal cancer.

The objective of the study was to estimate the cost of first line chemotherapy in metastatic colorectal cancer treated in the Gustave-Roussy Institute. Patients were randomized in the study FFCD 9601 with four schedules of treatment: Tomudex(R), 5FU weekly, LV5FU2 with low dose of folinic acid and LV5FU2 with high dose of folinic acid.

To compare by a prospective study in low risk polycythemia vera (PV) patients alone two drugs: hydroxyurea and pipobroman. Toxicity, efficiency, and leukemogenic potential were studied.

This multicentric double-blind, dose-ranging study was to compare efficacy and safety of two oral doses of granisetron solution in the prevention of chemotherapy-induced emesis in children with malignant diseases : 294 children, aged 1 to 16, treated with a moderately or highly emetogenic chemotherapy were randomly assigned to receive oral granisetron either 20 microg/kg (n = 143) or 40 microg/kg (n = 151) before and 6 to 12 hours after the start of chemotherapy. Fifty-one percent of patients treated with 20 microg/kg bd of oral granisetron solution achieved a complete response (no vomiting, no worse than mild nausea, no rescue therapy and no withdrawal during the specified period) and 59% achieved a major response (no more than one episode of vomiting, no worse than mild nausea, no rescue therapy and no withdrawal during the specified period). There was no difference between the two oral doses of granisetron. Treatment was rated as good or very good by investigators in 70% of cases. In conclusion, oral granisetron suspension either at 20 microg/kg bd or at 40 microg/kg bd showed good efficacy and safety in the prevention of chemotherapy-induced emesis in children with malignant diseases. Oral granisetron solution can be used as prophylaxis of emesis in children receiving moderately or highly emetogenic chemotherapy.

The complete or quasi complete resection of peritoneal carcinomatosis (PC) followed with IPCH is potentially able to cure some patients with a disease confined to the peritoneum. The aim of this prospective phase I-II study was to elaborate an efficient IPCH procedure with a good thermal homogeneity and a good spatial diffusion, which should be reproductible (and so standardizable and exportable), and to appreciate its tolerance and its carcinologic impact.

In the treatment of anal canal carcinoma, since the work of Nigro, the 5-fluorouracil-mitomycin C regimen is considered standard when applied concomitantly with radiotherapy. Surgery is used mainly to salvage the failures after irradiation. Two randomized European trials (EORTC, UKCCCR) have shown that the 5-fluorouracil-mitomycin C combination improves local control but not overall survival. The RTOG-ECOG trial has shown that mitomycin C improves local control when compared to 5-fluorouracil alone. This chemotherapy is responsible for a toxic death in 2% of cases. The 5-fluorouracil-cisplatin regimen will possibly represent an alternative to the 5-fluorouracil-mitomycin C. Ongoing trials will help to answer this question.

NEED FOR NEW CHEMOTHERAPY AGENTS: Metastasic breast cancer is an excellent model for studying anticancer agents: chemotherapy or hormonotherapy or compounds modifying the organism's response. If no adjuvant treatment is given after locoregional treatment of breast cancer, metastasis will develop within 10 years in 30% of the patients free of initial nodal invasion and within 5 years in 50% of the patients with initial nodal invasion. ADJUVANT TREATMENTS: Hormonotherapy and chemotherapy reduce mortality due to breast cancer by 10%. New adjuvant agents have been recently introduced. Taxans (docetaxel, paclitaxel) are the most active molecules since antracyclines. New aromataase inhibitors include letrozole and anastrozole. Their efficacy has been demonstrated in phase II and phase III trials, allowing their experimentation as adjuvant treatments.

Comparative efficacy and safety of 2 LHRH analogues in metastatic prostatic carcinoma.