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M Ducreux

Publications and source records attributed to M Ducreux.

At least 109 records · Page 6Linked to original sources
PubMed1997

[Recent advances in adjuvant chemotherapy in colonic cancers].

Carcinoma of the large bowel is one of the most common malignant disease. In France, 15,000 died each year from the metastatic or locoregional progression of this cancer. In the past, effective surgical adjuvant therapy has been an elusive goal with no evidence of benefit from chemotherapy or immunotherapy. However, a meta-analysis published in 1988 showed that one-year adjuvant chemotherapy using 5-fluorouracil (5-FU) containing regimens may slightly improve survival. Accelerated progress has been made since 1990: in colon cancer with regional nodal metastasis (stage C tumor), therapy with combined 5-FU and levamisole has resulted in a 33% reduction in the death rate. Controlled clinical trials demonstrated improved tumor response rates when the combination of 5-FU and leucovorin was compared with single-agent 5-FU in patients with metastatic colorectal cancer. Recent results indicate that this combination is effective in preventing tumor relapse and improving survival in patients with high risk colon cancer (especially stage C tumor). The comparison of 5-FU and leucovorin to 5-FU and levamisole is ongoing; the preliminary results of these controlled trials showed that 6 months of adjuvant therapy with 5-FU and leucovorin is as effective as the standard 12 months 5-FU and levamisole regimen and less toxic. No clear adjuvant benefit has been established in patients with Dukes' stage B2 colon cancer. The lack of statistical power of the trials and the 80% overall survival rate of these patients may explain these negative results. Almost all the specialists of these tumors considered that it is possible to select patients who are at sufficiently high risk of recurrence so that treatment can be justified. These patients are those who presented initially with tumor perforation or obstruction, adherence to or invasion of adjacent organs, young patients. Clinical trials suggest a survival benefit from the direct portal administration of the 5-FU in the immediate post-operative period, although the magnitude of the effect is less than that seen in the systemic therapy trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Peritoneal carcinomatosis treatment with curative intent: the Institut Gustave-Roussy experience.

The prognosis of peritoneal carcinomatosis (PC), classically treated with intravenous chemotherapy, is very poor (mean survival of 6 months). The aim of this study is to report the results of a phase II study in which PC was treated with complete cytoreductive surgery, with the residual microscopic disease treated by immediate intraperitoneal post-operative chemotherapy (IIPC) for 5 days (mitomycin with fluorouracil or Adriamycin with Platinol. Fifty-four patients with PC from miscellaneous origins were treated between January 1993 and April 1996. The PC was important (clinically evident) but with no extraperitoneal localization in 29 cases. The PC was moderate or minor in 25 cases having been fortuitously discovered during a laparotomy for extraperitoneal cancer localization. Operating time was 7:21 h, associated frequently with extensive peritonectomies, and with resection of invaded organs (four organs per patient). IIPC was complete (5 days) in 91 per cent of patients. Three post-operative deaths (5.5%) occurred. Morbidity was present in 61 per cent of patients, and was related to surgical extension (P < 0.001). A 2-year survival of 50% was mainly correlated with the importance of the PC (P < 0.01), and was the same for both groups of patients (isolated major PC vs moderate (or minor) PC associated with extraperitoneal localization). PC recurrence rates were 30 per cent at 2 years. Complete cytoreductive surgery associated with IIPC is a logical and promising treatment of moderate and minor PC. However, it appears that it is a heavy treatment for patients (and physicians), and its efficacy will be proved only after a randomized study for survival, quality of life, and cost (currently ongoing).

Adult↗
PubMed1997

5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration. Final results of a randomised trial in metastatic colorectal cancer.

The aim of this Phase III, balanced randomised trial was to compare continuous intravenous infusion (CVI) of 5-FU with bolus (B) administration for metastatic colorectal cancer (CRC). One hundred and fifty-five non-pretreated patients were randomised to receive CVI 5-FU at a dose of 750 mg/m2/day (d), 7 d every 21 d (n = 77), or bolus 5-FU 500 mg/m2/d x 5 d every 28 d (n = 78). Incremental dose escalation at 50 mg per step was recommended in the absence of toxicity. All the patients had measurable metastatic disease (M), particularly, liver and a good performance status (WHO grade 0-1). Dose intensity was significantly higher in CVI than in the bolus group: 1369 mg/m2/week versus 558 mg/m2/week (P = 0.0001). Grade II-IV stomatitis was more frequent in the CVI group (31% versus 9%; P < 0.0001) as was hand and foot syndrome (14% versus 3%; P < 0.001). Diarrhoea (22% versus 12%) and grade III granulocytopenia (2% versus 6%) were comparable. Responses were more frequent in the CVI (26%) than in the bolus group (13%) (P < 0.04); progression-free survival was higher for the CVI group (P = 0.04), but there was no statistical difference in overall survival (median: 10 months (m) compared to 9 m), and 1 year survival (SD) 42% (6%) versus 40% (6%). In the multivariate analysis, survival was better for patients with a good PS, well-differentiated adenocarcinomas and a primary tumour without serosal extension. In conclusion, with a higher dose intensity, CVI 5-FU improved tumour control, but not overall survival.

Antimetabolites, Antineoplastic↗
PubMed1997

Preliminary results of a phase II study of high-dose radiation therapy and neoadjuvant plus concomitant 5-fluorouracil with CDDP chemotherapy for patients with anal canal cancer: a French cooperative study.

BACKGROUND: Chemotherapy (5-fluorouracil-mitomycin C) concomitant with radiotherapy (RT) increases local control and colostomy-free survival in advanced anal canal carcinomas (ACC). The purpose of this prospective trial was to analyse the toxicity of and response to an induction chemotherapy combining 5-fluorouracil (5-FU) and CDDP administered concomitantly with irradiation. PATIENTS AND METHODS: Thirty patients (24 F/6 M, mean age 60, range 38-74) with an advanced ACC > 40 mm and/or with node involvement were prospectively treated (1 T1, 16 T2, 8 T3, 5 T4, 10 N1, 1 N2, 8 N3) from November 1994 to January 1996. Two induction and two concomitant cycles of 5-FU (800 mg/ m2 D1-4 infusion) and CDDP (80 mg/i.v./m2 at D1) were delivered. RT consisted of 45 Gy (1.8 Gy/fr, 5 fr/w) on pelvis +/- inguinal nodes or 30 Gy (3 Gy/fr, 4 fr/w) by direct perineal field. A boost (15-20 Gy) was delivered six weeks later. RESULTS TOXICITY: one patient died of a pulmonary embolism on D4. The remaining 29 received the entire treatment, with reduced 5-FU doses in 11 patients because of acute toxicity. The RT boost was delayed for one patient (aplasia). In 109 cycles, 3 grade 4 and 17 grade 3 toxicities were observed; there were no toxic deaths. Tumor response: the complete response (CR) and partial response (PR) rates were, respectively, 11% and 61% after induction chemotherapy, 59% and 31% after concomitant radiochemotherapy and 96% and 0% two months after completion of the treatment. No tumor progression was observed. CONCLUSION: the treatment was well tolerated and there was good compliance. After induction chemotherapy, most of the patients were in PR, with some even in CR. After completion of the treatment all but one were in CR. The tumor response and the long term results of 50 patients will be analysed before initiation of a randomised trial is considered.

Adult↗
PubMed1997

Self-expanding metallic stents as palliative treatment of malignant gastroduodenal stenosis.

OBJECTIVE: Our objective was to evaluate the efficacy of self-expanding metallic stents as palliative treatment in 10 patients with malignant stenosis of the stomach (n = 2) or the duodenum (n = 8). CONCLUSION: Metallic stents appeared valuable for the treatment of malignant gastroduodenal stenosis in this preliminary study because they provided durable relief of symptoms in eight of 10 patients for a mean of 93 days, until death. Particular attention should be paid to evaluating the digestive tract meticulously downstream because this zone was the cause of failure in two patients. Further studies are needed using a larger series.

Abdominal Neoplasms↗
PubMed1997

[Peritoneal carcinosis treated by complete excision and immediate postoperative intra-peritoneal chemotherapy. Phase II study in 54 patients].

OBJECTIVES: The short term prognosis of peritoneal carcinomatosis whose classical treatment is intravenous chemotherapy, is poor (mean survival of 6 months). The aim of this study was to report the results of a phase II prospective study in which peritoneal carcinomatosis was managed with complete reductive surgery associated with treatment of the residual microscopic disease with immediate intraperitoneal postoperative chemotherapy. PATIENTS AND METHODS: Fifty-four patients with peritoneal carcinomatosis from miscellaneous origins, were treated between January 1993 and April 1996. Major peritoneal carcinomatosis was important, clinically evident, but without extraperitoneal localization in 29 cases. It was moderate, fortuitously discovered during a laparotomy for an extraperitoneal recurrence in 25 cases. Immediate intraperitoneal postoperative chemotherapy was carried out continuously during 5 days, with 900 ml/m2 of ringer lactate, with either mitomycine C and 5-fluorouracil, or doxorubicin and platinum, according to histology. The treatment was complete in 91% of cases. RESULTS: Three patients died during the hospitalization (5.5%), and a high morbidity (61%) was observed, with 35% intra-abdominal complications necessitating surgery in 13% of the patients. The postoperative complications were correlated with the extension of the cytoreductive surgery (P < 0.001). After a mean follow-up of 12.3 months, 13 patients died. The 2-year survival rate was 50%. Survival was related to the importance of the peritoneal carcinomatosis (P < 0.01) and was identical for patients with isolated peritoneal carcinomatosis and for patients with moderate peritoneal carcinomatosis associated with resected extra-peritoneal disease. The incidence of recurrence of peritoneal carcinomatosis was 30% at 2 years, showing the efficiency of this new procedure to treat peritoneal carcinomatosis. CONCLUSIONS: Complete cytoreductive surgery with immediate intraperitoneal postoperative chemotherapy is a promising treatment of peritoneal carcinomatosis. However it appears that: a) it is a difficult treatment for patients and for physicians, b) its efficiency will be asserted only with a randomized study (currently ongoing), that only allows to suppress selection bias, c) it is able to cure some groups of peritoneal carcinomatosis (probably 20%), that will be difficult to identify, and d) improvement of immediate intraperitoneal postoperative chemotherapy is possible (mainly with hyperthermia). The main advantage of immediate intraperitoneal postoperative chemotherapy is that, after proving its efficiency, easy widespread use will be assured.

Adult↗
PubMed1996

[Hepatic metastases of colorectal cancers: intra-arterial chemotherapy. Value and indications].

Intraarterial hepatic chemotherapy (IAHC) increases the tumoral exposure of the liver metastases to cytotoxic agents. IAHC may be used in case of non resectable and isolated liver metastases from colorectal origin. It gives a tumor response rate of about 50%. Seven phase III trials and a recent metaanalysis testing IAHC using FUDR demonstrated its superiority over systemic chemotherapy using FUDR or bolus 5FU in terms of response rate and an increase in survival compared to symptomatic treatment. IAHC drawbacks are the biliary toxicity observed with some protocols, the development of extrahepatic metastasis and its cost. The ongoing protocols aim to improve the IAHC efficacy and tolerance and are frequently associated to systemic chemotherapy. The discovery of new active products in colorectal cancer and the optimisations of combinations of 5FU and leucovorin in terms of efficacy stimulate research aimed at developing more active combinations of IAHC and active systemic chemotherapy. The best IAHC indications are presently unresectable hepatic metastases from colorectal cancer without extra-hépatic metastases, with less than 50% liver involvement, with a CEA level under 100 ng/ml.

Antineoplastic Agents↗
PubMed1996

[Value of endorectal ultrasonography in the treatment of rectal tumors].

OBJECTIVES: To determine the diagnostic accuracy of endosonography and to appreciate its influence on the therapeutic strategy. METHODS: Sixty-two patients referred to the gastroenterology unit between April 1990 and February 1995 for a rectal tumor. Thirty-two patients did not receive any preoperative treatment (group A) and 30 were treated by radiotherapy or chemoradiotherapy before surgery (group B). Transrectal ultrasonography was performed with a Bruel and Kjaer device. RESULTS: Diagnostic accuracy for parietal infiltration was 84% for the entire series, 94% for group A and 73% for group B. Diagnostic accuracy of lymph node invasion was 71% for the entire series, 81% and 60% for groups A and B, respectively. It is highly probable that a histopathologic down-staging due to preoperative treatment explained the results in the group B. Using a pragmatic approach which combined the results for parietal infiltration and for lymph node invasion, transrectal ultrasonography would have correctly selected 20 among the 25 patients who could have been treated by local excision. The use of this same pragmatic approach in patients with high risk of local recurrence enabled correct selection of 26 among the 32 exposed patients. CONCLUSION: We conclude that transrectal ultrasonography: 1. is a reliable technique for the pretherapeutic staging of rectal cancer, especially for the assessment of parietal infiltration. Progress is needed for the diagnosis of lymph node invasion; 2. selects well the patients who can be treated by local excision; 3. is a reliable technique for the selection of patients who need preoperative treatment.

Evaluation Studies as Topic↗
PubMed1996

Liver abscess formation after local treatment of liver tumors.

Our goal was to determine a subset of patients at high risk of developing liver abscesses after local treatment of liver tumors (LTLT) and establish guidelines for the conduct of LTLT in the safest conditions in such patients. Five hundred sixty-one LTLT, 489 transhepatic arterial chemoembolizations (TAC, 10 hepatic embolizations, and 62 percutaneous intratumor injections (PIT), were retrospectively reviewed for liver parenchyma necrosis and abscess formation. Four patients developed abscesses, three after TAC and one after PIT. Despite broad-spectrum antibiotherapy, percutaneous drainage, and surgery, two patients died. A left hepatectomy was required in the other two patients for cure. All four patients had a carcinoid or a neuroendocrine pancreatic tumor. Three out of four patients had bilioenteric anastomoses, and the fourth had recently undergone cholecystectomy and papillotomy. A Lipiodol/doxorubicin mixture without any particulate embolization was injected in the three patients who developed abscesses after TAC. LTLT in patients with bilio enteric anastomosis or papillotomy and/or neuroendocrine or carcinoid tumor should be performed with strict precautions during the procedure and for peri-procedural care.

Antineoplastic Agents↗
PubMed1996

Treatment of the carcinoid syndrome with the longacting somatostatin analogue lanreotide: a prospective study in 39 patients.

BACKGROUND: Somatostatin analogues effectively control flushing and diarrhoea in patients with the carcinoid syndrome. The octapeptide lanreotide is available in slow release form, which could eliminate the necessity of twice a day injections as with octreotide. PATIENTS AND METHODS: 39 patients with carcinoid syndrome were included in a prospective multicentre study. Patients received lanreotide 30 mg intramuscularly every 14 days for six months. The number and intensity of flushing episodes and bowel movements, urinary 5 hydroxy-indolacetic acid (5 HIAA) concentrations, and variations of tumour mass were recorded. RESULTS: After one month of treatment, flushing episodes (median (range)) decreased significantly (3 (0.3-24) episodes per day v 1 (0-15), p = 0.04) and completely resolved in 39% of the patients. A significant decrease was seen in the number of bowel movements and discomfort related to diarrhoea. Urinary 5 HIAA concentrations were unchanged in 57% of the patients and decreased in 18%. After six months of treatment, the actuarial proportions of patients with at least a 50% decrease in the number of flushing episodes and bowel movements were 54% and 56%, respectively. Forty two per cent of the patients who were treated for six months had at least a 50% reduction in 5 HIAA values. No clear signs of regression of tumours were seen in any of the patients. Lanreotide was well tolerated despite transient mild pain or erythema at the injection site in 25% of the patients. Biliary lithiasis appeared in two patients after six months of lanreotide. CONCLUSION: Lanreotide, 30 mg intramuscularly every other week, is an effective and convenient treatment in patients with the carcinoid syndrome.

Biomarkers, Tumor↗
PubMed1996

Quantification of tumor uptake of iodized oils and emulsions of iodized oils: experimental study.

PURPOSE: To optimize use of iodized oil for diagnostic computed tomography (CT) enhanced with iodized oil and for interstitial radiation therapy with iodine-131-labeled iodized oil, the authors quantified the distribution of iodized oil after injection of different formulations of iodized oil into the hepatic artery. MATERIALS AND METHODS: I-125-labeled iodinated ethyl ester of poppyseed oil in two viscosities (iodized oil ultrafluid [viscosity, 0.04 Pa/sec] and iodized oil fluid [viscosity, 0.17 Pa/sec]) was injected (pure forms and three different emulsions of each) into the hepatic artery of rabbits bearing VX2 tumors in the liver. All rabbits received a radiation dose of 4 MBq per kilogram of body weight in 0.1 mL/kg iodized oil. Animals were killed 4 days later, and iodized oil uptake was evaluated in the tumor, nontumorous liver, and lung. RESULTS: There were no statistically significant differences in uptake between pure iodized oil ultrafluid or fluid or between the same type of emulsions made with each type of iodized oil. Lung uptake was significantly higher with pure iodized oil ultrafluid and fluid (19.75 kBq/g +/- 3.25 [standard error of the mean] vs 19.48 kBq/g +/- 6.15, respectively) than with any emulsions (range, 3.72-8.14 kBq/g; mean, 5.68 kBq/g) except the small-droplet oil-in-water emulsion (10.51 kBq/g +/- 1.18). The ratio of tumor to nontumorous liver uptake of iodized oil was significantly higher with large-droplet water-in-oil emulsions made of iodized oil ultrafluid or fluid (10.26 +/- 2.88 and 9.53 +/- 0.64, respectively) than with any other product (range, 4.07-5.38; mean, 4.49). CONCLUSION: Use of large-droplet water-in-oil emulsions limited lung uptake and increased tumor uptake of iodized oil after intraarterial hepatic injection in rabbits bearing VX2 tumors in the liver.

Animals↗
PubMed1996

Surgery for lung metastases from colorectal cancer: analysis of prognostic factors.

PURPOSE: To identify prognostic factors of improved survival after resection of isolated pulmonary metastases (PM) from colorectal cancer. PATIENTS AND METHODS: A retrospective analysis of the records of all patients with PM from colorectal cancer who underwent thoracic surgery with curative intent before December 1992 at a single surgical center was performed. Univariate (log-rank) and multivariate (Cox's model) analyses of survival were used to identify significant prognostic factors. RESULTS: Eighty-six patients with PM from colon (n = 49) or rectal (n = 37) cancer underwent 102 thoracic operations, which included 21 bilateral and 10 incomplete resections. The 5- and 10-year probabilities of survival (Kaplan-Meier) after the first thoracic operation were 24% (95% confidence interval [CI], 15% to 35%) and 20% (95% CI, 13% to 31%), respectively. Sex, age, site of the primary tumor (colon or rectum), disease-free interval (DFI), and previous resection of hepatic metastases were found not to be statistically significant prognostic factors. Complete resection, a limited number ( < two) of PM, and a normal prethoracotomy serum carcinoembryonic antigen (CEA) level were predictors of a longer survival duration by univariate analysis, but only complete resection (P = .024) and preoperative CEA level (P = .001) were identified as independent prognostic factors by multivariate analysis. The estimated 5-year survival rate of patients with a normal prethoracotomy CEA level was 60%, as compared with 4% in cases with elevated ( > 5 ng/mL) CEA level. CONCLUSION: Besides resectability, the prethoracotomy serum CEA level appears the most reliable predictor of survival in patients with isolated PM from colorectal cancer.

Adenocarcinoma↗
PubMed1996

[Major hepatectomy after intra-arterial chemotherapy for initially unresectable liver tumors. Frequency, technical problems, results and indications].

BACKGROUND: Major hepatectomy after prolonged intra-arterial hepatic chemotherapy (IAHC) is extremely rare, because IAHC usually fails to reduce the tumor volume sufficiently or obtain a long duration of response, or both, and because it impairs hepatic function. The present report was done to study the frequency, feasibility and the results of hepatectomy following IAHC. STUDY DESIGN: This retrospective study consisted of 14 patients treated with at least six courses of IAHC (mean of 17.6, median of 13, range of six to 48 courses) for hepatic tumors: colorectal metastases (n = 9), apudoma metastases (n = 4), and hepatoblastoma (n = 1). Systemic chemotherapy was associated in eight cases during (n = 5), or after (n = 3) IAHC. Initially, multiple hepatic tumors were unresectable in ten cases. They eventually became resecable, but were associated with extensive extrahepatic sites of involvement in four cases. All patients underwent curative major hepatectomy after a careful and specific morphologic and functional hepatic assessment. Right portal vein embolization was performed preoperatively upon three patients, resulting in 38, 44 and 77 percent hypertrophy of the left lobe before hepatectomy. Hepatectomy was also performed upon three patients with hepatic arterial thrombosis induced by IAHC, after a careful workup of the neoarteriovascularization of the liver. RESULTS: These 14 cases only represented 5.8 percent of the 239 patients in whom a catheter was inserted for IAHC, and 4.2 percent of the 335 patients who had hepatectomy for carcinoma. Postoperatively, there was no mortality and no clinical hepatic insufficiency. However, ten complications occurred in eight patients (three of them resulted in reoperation). Histologic examination revealed substantial modifications of the hepatic parenchyma because of IAHC. Results concerning survival were very encouraging: five of the nine patients with metastases of the colon and rectum are free of disease, with a mean follow-up period of 36 months after the beginning of IAHC. CONCLUSIONS: The decision to perform a major hepatectomy after prolonged IAHC is difficult and must be based on an output morphologic assessment with computed tomographic portography and a careful evaluation of functional liver impairment because of IAHC (the therapeutic strategy proposed by Makuuchi for hepatectomy in patients with cirrhosis, based on indocyanine green clearance and volume to resect, is very useful for this purpose). Hepatectomy is technically difficult to perform following IAHC because of a flabby parenchyma and unusually high pressure in the small central hepatic veins. This draw-back is circumvented by using techniques: such as preoperative hypertrophy of the future remaining liver, a transparenchymatous approach of vasculobiliary structures, and intermittent clamping of the hepatic pedicle or vascular isolation of the liver. Postoperative complications occurred more frequently than after major, hepatectomy in other clinical settings (p < 0.05). However, as this therapeutic approach greatly increases survival, it should not be neglected by clinicians, although indications for its use are very rare.

Adult↗