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Biomedical subjects

L Bedenne

Publications and source records attributed to L Bedenne.

At least 19 recordsLinked to original sources
PubMed2006

Randomised trial comparing three different schedules of infusional 5FU and raltitrexed alone as first-line therapy in metastatic colorectal cancer. Final results of the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 trial.

LV5FU2 with high-dose leucovorin (LV), weekly infusional 5-fluorouracil (5FU) (AIO schedule) and raltitrexed have been demonstrated to be active agents in first-line treatment of colorectal cancer. We performed a 4-arm randomised trial to compare (1) a low-dose intravenous bolus of LV (20 mg/m2), followed by an intravenous bolus of 5FU (400 mg/m2), followed by a 22-hour continuous infusion of 5FU (600 mg/m2) on day 1 and day 2/2 weeks (ldLV5FU2 arm), (2) a weekly continuous infusion of high-dose 5FU (2.6 g/m2/week) for 6 weeks followed by a rest week (HD-FU arm) and (3) raltitrexed (Tomudex arm; 3 mg/m2/3 weeks) to standard LV5FU2. From 1997 to 2001, 294 patients were included. The 4 arms were well balanced for sex ratio, age, WHO performance status, the primary tumour site and prior adjuvant chemotherapy. Treatment was stopped due to low accrual. Two toxicity-related deaths were observed in the Tomudex arm. The treatments gave rise to different rates of grade 3-4 neutropenia (3, 4, 11 and 14% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively, p = 0.028), leucopenia and vomiting. At least one episode of grade 3-4 toxicity was observed in 27, 25, 38 and 47% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.016). An objective response was observed in 28, 21, 22 and 10% of the patients in the LV5FU2, ldLV5FU2, HD-FU and Tomudex arms, respectively (p = 0.04). Progression-free survival (PFS) of the patients in the Tomudex arm was statistically lower compared to that of patients treated with LV5FU2 or ldLV5FU2 (combined group; p = 0.013, log rank test). In conclusion, Tomudex is more toxic and yields shorter PFS than infusional 5FU. Despite the early closure of the study and the lack of power of the comparison, it seems that ldLV5FU2 could be considered as an active, easier and less expensive option for the treatment of metastatic colorectal cancer compared to classic LV5FU2 or weekly HD-FU.

Aged↗
PubMed2006

A comparative longitudinal quality of life study using the Spitzer quality of life index in a randomized multicenter phase III trial (FFCD 9102): chemoradiation followed by surgery compared with chemoradiation alone in locally advanced squamous resectable thoracic esophageal cancer.

BACKGROUND: The aim of the study was to compare the longitudinal quality of life (QoL) between chemoradiation with or without surgery in patients with locally advanced squamous resectable esophageal cancer included in a randomized multicenter phase III trial (FFCD 9102). MATERIALS AND METHODS: All patients with locally advanced resectable (T3-4 N0-1 M0) epidermoid or glandular esophageal cancer (n = 451) received induction chemoradiation. Responders (n = 259) were randomized between surgery (arm A) and continuation of chemoradiation (arm B). The Spitzer QoL Index was scored (0-10) at inclusion and at each follow-up, every 3 months during 2 years. QoL at baseline and longitudinal changes were respectively compared with univariate ANOVA and mixed-model analysis of variance for repeated measurements. The time interval between the follow-up was assessed and the same analyses were performed among survivors with 2 years of follow-up. RESULTS: The squamous histology was predominant in both arms. The mean QoL score decreased between baseline and the first follow-up and between the first and the second follow-ups. QoL scores at the first follow-up were comparatively worse in arm A than in arm B (7.52 versus 8.45, P < 0.01), whereas the longitudinal QoL study showed no difference between treatments (adjusted P = 0.26). Furthermore, the longitudinal QoL was not different (adjusted P = 0.23) among survivors with 2 years of follow-up. CONCLUSIONS: Among patients responding to induction chemoradiation, surgery and continuation of chemoradiation had the same impact on QoL in patients with locally advanced, resectable esophageal cancer although a significantly greater decrease in the Spitzer Index was observed in the postoperative period.

Adenocarcinoma↗
PubMed2005

Management and prognosis of esophageal cancers: has progress been made?

The aim of this study was to investigate time trends in treatment and prognosis of esophageal cancer in a well-defined French population. Data was obtained from the Burgundy Cancer Registry (France) and three time periods were defined: 1976-90, 1991-96 and 1997-2002. A logistic regression was used to identify factors associated with an R0 resection. A multivariate survival analysis was performed using a Cox model. From 1976 to 2002, 2267 patients were included. The R0 resection rate slightly increased from 20.9% to 25.8% (P=0.019) then remained stable. Operative mortality decreased from 11.7% to 6.7% (NS). Age and subsite significantly influenced the rate of resection for cure whereas period had no effect. Chemotherapy alone was seldom used and radiotherapy alone dramatically dropped over time. Chemoradiation used as adjuvant treatment increased from 16.3% (1976-90) to 30.6% (1997-02) (P<0.001) and as sole treatment from 16.0% to 48.5% (P<0.001). The 3-year survival rates were respectively 10.1% and 9.7% (NS). Age and stage at diagnosis influenced the prognosis of esophageal cancer whereas time period and histology had no influence. This study claims that esophageal cancer remains a serious cancer problem and no improvement has been seen in the study population in France in its management over time.

Adenocarcinoma↗
PubMed2005

Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801).

BACKGROUND: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy after resection for gastric cancer in a randomized controlled trial. PATIENTS AND METHODS: After curative resection, stage II-III-IVM0 gastric cancer patients were randomly assigned to postoperative chemotherapy or surgery alone. 5-Fluorouracil (5-FU) 800 mg/m(2) daily (5-day continuous infusion) was initiated before day 14 after resection. One month later, four 5-day cycles of 5-FU (1 g/m(2) per day) plus cisplatin (100 mg/m(2) on day 2) were administered every 4 weeks. RESULTS: The study was closed prematurely after enrollment of 260 patients (79.7% N+), owing to poor accrual. At 97.8 months median follow-up, 5- and 7-year overall survival were 41.9% and 34.9% in the control group versus 46.6% and 44.6% in the chemotherapy group (P=0.22). Cox model hazard ratios were 0.74 [95% confidence interval (CI) 0.54-1.02; P=0.063] for death and 0.70 (95% CI 0.51-0.97; P=0.032) for recurrence. An invaded/removed lymph nodes ratio >0.3 was the main independent poor prognostic factor identified by multivariate analysis (P=0.0001). Because of toxicity, only 48.8% of patients received more than 80% of the planned dose. CONCLUSION: There was no statistically significant survival benefit with this toxic cisplatin-based adjuvant chemotherapy, but a risk reduction in recurrence was observed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion compared to classical doxorubicin-Lipiodol: potential advantage for chemoembolization of unresectable hepatocellular carcinoma.

There is no well-defined curative treatment for advanced and unresectable hepatocellular carcinoma. The widely used transarterial chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not been shown to improve survival in randomized studies. Further, obstruction of the hepatic artery used in the procedure is badly tolerated in patients with cirrhosis. Drugs with a more rapid penetration into the cancer cells are likely to eliminate the need for obstruction of the hepatic artery. We therefore compared the cytotoxicity of another anthracycline pirarubicin with that of the commonly used doxorubicin. In this report, we show that pirarubicin has a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is more stable at 37 degrees C than doxorubicin-Lipiodol. Moreover, pirarubicin accumulates at a greater extent in the oil phase, permitting Lipiodol to act as a slow-releasing vector for the anthracycline. Further, amiodarone, a multidrug resistance inhibitor, was shown to decrease the intrinsic resistance of HepG2 and Hu-H7 cells to both anthracyclines, and the presence of polysorbate 80 in the amiodarone preparation increased the stability of the anthracycline-Lipiodol emulsions. We therefore conclude that pirarubicin is a better candidate for TACE than doxorubicin. The rapid and increased cytotoxicity of pirarubicin on hepatoma cancer cells and the stability of the pirarubicin-Lipiodol amiodarone emulsion could avoid the complete obstruction of the hepatic artery by Gelfoam sponges, and provide a better tolerated method of TACE in patients with latent liver insufficiency.

Amiodarone↗
PubMed2001

Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution administered in balloon-occluded hepatic artery: experimental rationale and clinical pilot study.

Reduced osmolarity in incubation medium was previously shown to increase in vitro cellular accumulation and cytotoxicity of cisplatin on cancer cells. We confirmed in the present work that cisplatin diluted in an hypotonic 25 g/l glucose solution (124 mOsm) was dramatically more cytotoxic in vitro than cisplatin diluted in normotonic 9 g/l NaCl (300 mOsm) on the human HT29 colon and MCF7 breast cancer cells. We conducted then a pilot clinical study on the administration of cisplatin diluted in hypotonic 25 g/l glucose solution given through the balloon-occluded hepatic artery for the treatment of liver metastases from colon or breast cancer tumors. Nine patients (5 men, 4 women; mean age 58, range: 44-71) with confirmed isolated, unresectable metastases from colorectal (7) or breast (2) tumors were included in this study and a total of 23 cycles were administered (2.55 per patient; range 1-5) with an average dose of 50 mg cisplatin (range: 12.5-100). Hepatic artery dissection due to balloon injury with partial or complete arterial obstruction were encountered in 2 patients. Pain in the liver and epigastric area was the main symptom which was constant and intense during the IAH cisplatin injection. Fever > 38 degrees C was observed in 15/23 cycles and increase of creatinine in 1/23 cycles. Transient increase of hepatic transaminases without change in prothrombin time was registered in all patients. However one patient who received the highest dose of 100 mg cisplatin developed a persistent but reversible clinical jaundice and a transient increase in prothrombin time. One patient achieved a partial response (12 weeks), 7 had stable disease (mean duration: 6 weeks) and one had a progressive disease. Hepatic arterial infusion of cisplatin diluted in hypotonic 25 g/l glucose solution and administered through the balloon-occluded hepatic artery is a feasible approach. Total dose of cisplatin in hypotonic glucose solution will not exceed 80 mg by cure in a further phase II study.

Adult↗
PubMed2000

High dose rate brachytherapy for superficial cancer of the esophagus.

PURPOSE: We analyzed our experience with external radiotherapy, combined modality treatment, or HDR brachytherapy alone to limited esophageal cancers. METHODS AND MATERIALS: From 1991 to 1996, 25 patients with limited superficial esophagus carcinomas were treated by high dose rate brachytherapy. The mean age was 63 years (43-86 years). Five patients showed superficial local recurrence after external radiotherapy. Eleven patients without invasion of the basal membrane were staged as Tis. Fourteen patients with tumors involving the submucosa without spreading to the muscle were staged as T1. Treatment consisted of HDR brachytherapy alone in 13 patients, external radiotherapy and brachytherapy in 8 cases, and concomitant chemo- and radiotherapy in 4 cases. External beam radiation was administered to a total dose of 50 Gy using 2 Gy daily fractions in 5 weeks. In cases of HDR brachytherapy alone (13 patients), 6 applications were performed once a week. RESULTS: The mean follow-up is 31 months (range 24-96 months). Twelve patients received 2 applications and 13 patients received 6 applications. Twelve patients experienced a failure (48%), 11/12 located in the esophagus, all of them in the treated volume. One patient presented an isolated distant metastasis. In the patients treated for superficial recurrence, 4/5 were locally controlled (80%) by brachytherapy alone. After brachytherapy alone, 8/13 patients were controlled (61%). The mean disease-free survival is 14 months (1-36 months). Overall survival is 76% at 1 year, 37% at 2 years, and 14% at 3 years. Overall survival for Tis patients is 24% vs. 20% for T1 (p = 0.83). Overall survival for patients treated by HDR brachytherapy alone is 43%. One patient presented with a fistula with local failure after external radiotherapy and brachytherapy. Four stenosis were registered, two were diagnosed on barium swallowing without symptoms, and two required dilatations. CONCLUSION: High dose rate brachytherapy permits the treating of patients with superficial esophageal cancer with good tolerance. Early tumors, located in the mucosa, might be treated by HDR brachytherapy alone or by a combined modality treatment in which HDR brachytherapy can take place like a boost. This approach may cure localized recurrences.

Adenocarcinoma↗
PubMed2000

[Concurrent concentrated radio-chemotherapy of epidermoid cancer of the esophagus. Long-term results of a phase II national multicenter trial in 122 non-operable patients (FFCD 8803)].

OBJECTIVES: Concomitant radiochemotherapy improves survival from inoperable esophageal cancer compared to radiotherapy alone. Several regimens of radiotherapy (standard or concentrated split course radiotherapy) are used, however the optimum protocol remains to be determined. The aim of this study was to analyze the efficacy and tolerance of concentrated concomitant split course radiochemotherapy. Prognostic factors as well as those positively influencing complete response were also studied. METHODS: This multicentric phase II trial looked at patients with histologically proven, inoperable, squamous cell esophageal carcinoma without metastases or invasion of the tracheobronchial mucosa. Treatment included 3 cycles of chemotherapy by 5-FU continuous infusion (800 mg/m2.d D1-D5, D22-D26, D43-D47), cisplatin (70 mg/m2 D2, D23, D44) and radiotherapy 15 Gy/5d (D1-D5, D22-26, D43-D47). Efficacy was analyzed by endoscopy, biopsy and computerized axial tomography during the 12th week of treatment. RESULTS: The trial included 122 patients from 21 centers (110 M and 12F, mean age 63.1 +/- 8.6 years, range 40-78). In accordance with the TNM-UICC classification (1978), 8 patients were classified stage I (T1 N0), 13 stage II (T2 N0), 100 stage III (T3 and/or N1) and stage was unknown in 1 patient. Median follow-up was 63 months. Treatment was complete in half of the patients. 5 premature deaths (4.1%) were recorded over the treatment period, one of which was directly linked to the toxicity of the treatment. 16% of patients showed at least one severe side-effect. 117 patients received all 3 cycles of the treatment, 88 of them without delay, and all were evaluated. 58 (47.5% of the patients included) showed a complete response with a negative biopsy, 36 (29.5%) showed a partial response, 13 (10.7%) were stable and 10 (8.2%) showed progressive disease. The median duration of complete responses was 11.5 months. Symptomatically, dysphagia improved in 80% of the cases, performance status in 40%, and weight gain was observed in 30% of the patients with weight loss. At evaluation, oral feeding was impossible in 4 patients only and possible in 113 patients; however, endoscopic treatment of the dysphagia remained necessary in 28 patients. Median survival in the 122 patients included was 13.0 +/- 1.6 months and survival rates were 52.9, 29.8 and 12.1% at 1, 2 and 5 years, respectively. Three pretherapeutic prognostic factors influenced survival in a multivariate analysis: initial severe dysphagia (risk of premature death increased 3-fold in the first year), circumferential extension and the differentiated nature of the tumor (risk of death doubled regardless of the time delay). Factors influencing a complete clinical response were an early tumor stage, a poorly differenciated tumor in patients older than 65, and no circumferential extension. The risk of recurrence was 54.8% at 1 year in the 58 patients with complete remission. Complete circumferential extension and a well or moderately differentiated tumour influenced recurrence. CONCLUSION: This trial confirms the efficacy and good tolerance of concentrated split course radiochemotherapy in patients with inoperable esophageal cancer with a 5-year survival rate of 12%. This reinforces the need for a comparative trial (split course irradiation vs standard irradiation) such as the one currently being conducted in France.

Adult↗
PubMed1999

[Monitoring colorectal cancer after surgical resection].

POSTOPERATIVE FOLLOW-UP: Despite adjuvant therapy, approximately 50% of all patients undergoing curative surgery for Dukes C colorectal cancer will develop a recurrence within 3-5 years and 95% of these will die from their cancer shortly thereafter. ENDOSCOPY: Generally performed every 3 years after checking that all cancerous foci have been removed, colonoscopy is required to detect adenomes and metachronic cancers. Its contribution to screening for local recurrence is however rather limited since most recurrences develop in an extraluminal localization. CEA: Assayed at 8 months, repeated carcinoembryonic antigen assay can detect asymptomatic recurrence in 50 to 60% of the cases, usually 4 to 8 months prior to other explorations. Specificity is high (85% to 95% depending on the series), allowing exploratory laparotomy if CEA alone is elevated. However, the only randomized study evaluating CEA was unable to demonstrate any prolongation of survival with monthly tests. OPTIMAL FOLLOW-UP: There is some debate about the usefulness of intensive clinical and radiographic follow-up as the 4 randomized studies available were unable to demonstrate any beneficial effect. It must be noted however that the number of patients included in these studies was too low to evidence a small improvement in survival rates. In France, a 6% improvement at 5 years would result in 200 fewer deaths due to Duke C colorectal cancer annually. A large multicentric randomized study will be initiated shortly in France to evaluate the impact of intensive CEA monitoring versus no monitoring and intensive versus periodical radiological follow-up.

Carcinoembryonic Antigen↗
PubMed1999

[Cronkhite-Canada syndrome and arsenic poisoning: fortuitous association or new etiological hypothesis?].

We report a case of Cronkhite-Canada syndrome in a 66 year-old man, particular by an association with arsenism. Both arsenism and the Cronkhite-Canada syndrome are a cause of ectodermal and mucosal lesions. The persistence of physical, biological and endoscopic manifestations associated with disappearance of arsenic intoxication signs allowed us to make the diagnosis. The search of arsenic in blood, nail and hair must complete the investigations in case of acquired pseudopolyposis and ectodermal changes.

Aged↗
PubMed1998

[Cisplatin, 5-FU and preoperative radiotherapy in esophageal epidermoid cancer. Multicenter phase II FFCD 8804 study].

OBJECTIVES: The aim of this study was to analyze the efficacy and tolerance of preoperative radiochemotherapy in esophageal squamous cell carcinoma. Patterns of recurrence and prognostic factors were also studied. PATIENTS AND METHODS: This multicentric phase II trial included patients deemed operable. Preoperative treatment associated 5-FU 800 mg/m2/d by continuous infusion, cisplatin 20 mg/m2/d and radiotherapy 3 Gy/d D 1-5 and D 22-26. Resection was planned 50 to 60 days after the beginning of therapy. RESULTS: Seventeen centers accrued 96 patients, mean age 55.4 years. According to UICC 1978 classification: stage I 13%, stage II 53% and stage III 30%. Mean follow-up was 73 months. Pre-operative treatment was delivered at full dose in half of the patients. Ten percent of the patients did not receive the second cycle. Toxicity reached grade 3 in 23% and grade 4 in 7% of the patients. Two preoperative deaths occurred. Curative resection was performed in 82% of the patients. Operative mortality was 9%. tumors were sterilized on the operative specimen in 20% of the patients and microscopic remnants were observed in 13%. Preoperative clinical work-up overestimated histologic response in 10% of the cases underestimated it in 29%. After 2 years, a recurrence was observed in 56% of the patients: loco-regional in 30%, metastases in 19% and both in 7%. Median survival was 17 months and survival rates were 58% at 1 year and 25% at 5 years. Four prognostic factors influenced survival in multivariate analysis (Cox model): hematological toxicity grade 3 or 4, no complete response, circumferential extension > 2/3 and nodes visible on CT-scan. Factors positively influencing complete response were in multivariate analysis: a fungating tumor, weight loss < 8% and a full dose preoperative treatment. CONCLUSION: In this study, preoperative treatment associating 5-FU-cisplatin and radiotherapy allowed a high resectability rate, with one third of patients achieving complete or nearly complete histologic response. A randomized study is warranted to know whether this combined treatment is better than surgery alone.

Adult↗