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Biomedical subjects

P Rougier

Publications and source records attributed to P Rougier.

At least 19 recordsLinked to original sources
PubMed1998

Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. European Organisation for Research and Treatment of Cancer Gastrointestinal Tract Cancer Cooperative Group, the Gruppo Interdisciplinare Valutazione Interventi in Oncologia, and the Japanese Foundation for Cancer Research.

BACKGROUND: There is conflicting evidence on the efficacy of regional adjuvant chemotherapy, via portal-vein infusion (PVI), after resection of colorectal cancer. We undertook a randomised controlled multicentre trial to investigate the efficacy of PVI (500 mg/m2 fluorouracil plus 5000 IU heparin daily for 7 days). METHODS: 1235 of about 1500 potentially eligible patients were randomly assigned surgery plus PVI or surgery alone (control). The patients were followed up for a median of 63 months, with yearly screening for recurrent disease. The primary endpoint was survival; analyses were by intention to treat. FINDINGS: 619 patients in the control group and 616 in the PVI group met eligibility criteria. 164 (26%) control-group patients and 173 (28%) PVI-group patients died. 5-year survival did not differ significantly between the groups (73 vs 72%; 95% Cl for difference -6 to 4). The control and PVI groups were also similar in terms of disease-free survival at 5 years (67 vs 65%) and the number of patients with liver metastases (79 vs 77%). INTERPRETATION: PVI of fluorouracil, at a dose of 500 mg/m2 for 7 days, cannot be recommended as the sole adjuvant treatment for high-risk colorectal cancer after complete surgical excision. However, these results cannot eliminate a small benefit when PVI is used at a higher dosage or in combination with mitomycin.

Aged↗
PubMed1998

Are there indications for intraarterial hepatic chemotherapy or isolated liver perfusion? The case of liver metastases from colorectal cancer.

Intraarterial hepatic chemotherapy (IAHC) has been used for many years to treat liver tumors (primary or secondary) if no extrahepatic extension exists, when no resection is feasible, and when no active systemic chemotherapy is available. Liver metastases from colorectal cancer represent one of the best indications, and many trials have demonstrated that IAHC is an efficient treatment. Some of these trials were randomized and have demonstrated that IAHC significantly increases the response rate using IA FUDR compared to its systemic administration, and increases the overall survival compared to symptomatic treatment or systemic bolus 5FU. Liver toxicity and extrahepatic progression are the two main limiting factors which can be reduced using new protocols and combinations with systemic chemotherapy. New drugs such as THP adriamycin will become available for IAHC in the future. Isolated liver perfusion adds to IAHC an extracorporal extraction and allows the use of higher doses of chemotherapy. Its efficacy has been suggested in small phase II trials; however, its relative complexity and the lack of clear demonstration of its efficacy compared to the most recent and effective systemic chemotherapies used alone or in combination with IAHC prevent the recommendation of its use outside clinical trials. IAHC and isolated liver perfusion are two active locoregional treatments which can be combined with surgical resection and/or systemic chemotherapy and warrant further development, if possible, in randomized trials.

Antineoplastic Agents↗
PubMed1998

Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial. Groupe CHC.

BACKGROUND/AIMS: Lipiodol chemoembolization is a widely used method of treatment in patients with unresectable hepatocellular carcinoma, but its efficacy is still debated. The aim of our study was to assess the efficacy of lipiodol chemoembolization in patients with unresectable hepatocellular carcinoma. METHODS: Seventy-three patients with unresectable hepatocellular carcinoma, but without severe liver disease or portal vein occlusion, were randomly assigned to receive either repeated lipiodol chemoembolization (lipiodol, cisplatin (2 mg/kg), lecithin, and gelatin sponge injected into the hepatic artery) plus tamoxifen (40 mg) or tamoxifen alone. The main end-point was survival. RESULTS: The 37 patients in the lipiodol chemoembolization group received 104 courses (median 3 per patient). By 1 September 1996, 58 patients had died: 30 in the lipiodol chemoembolization group and 28 in the tamoxifen group. There was no difference in survival between the two groups (p=0.77). The relative risk of death in the lipiodol chemoembolization plus tamoxifen group as compared to the tamoxifen group was 0.92 (95% confidence interval 0.55 to 1.56). At 1 year, survival was 51% and 55%, respectively. An objective tumoral response was more frequently observed in the lipiodol chemoembolization group than in the tamoxifen group (24 versus 5.5%, respectively, p=0.046). Lipiodol chemoembolization caused two deaths and induced signs of liver failure in 51% of the patients assigned to this treatment. CONCLUSION: In our randomized study, lipiodol chemoembolization did not improve the survival of patients with unresectable hepatocellular carcinoma treated with tamoxifen.

Adult↗
PubMed1998

Effective treatment of advanced biliary tract carcinoma using 5-fluorouracil continuous infusion with cisplatin.

BACKGROUND: The combination of 5-fluorouracil (5-FU) and cisplatin has shown great activity in many different types of tumour with an in vitro synergistic effect between 5-FU and cisplatin. A phase II study of 5-FU plus cisplatin was performed in 25 previously untreated patients with inoperable locally advanced or metastatic biliary tract carcinoma. PATIENTS AND METHODS: Twenty-five patients, 10 of them men and 15 women with a median age of 58, were entered into the study. The chemotherapy regimen consisted of 5-FU: 1 g/m2/day in continuous intravenous (i.v.) infusion for five consecutive days, and cisplatin: 100 mg/m2/day on day 2 in a one-hour infusion with standard hyperhydration. Twenty-two patients had metastatic tumours and three had locally advanced disease. RESULTS: Of the 25 patients entered into the study, 24 were evaluable for response and 25 for toxicity. Nausea and vomiting was the main toxic side effect in 19 patients. Severe, WHO grade 3-4 thrombocytopenia or neutropenia were observed in three and seven patients, respectively. There were no toxic deaths. Of 25 patients, six had partial remissions (overall response 24%, 95% confidence interval 7%-41%). For three patients, tumour reduction permitted local radiotherapy and one of these patients with initially advanced disease is still alive six years after the beginning of treatment. CONCLUSIONS: This study, one of the largest phase II trials performed in this disease, shows interesting activity of the combination of 5-FU and cisplatin in advanced biliary tract carcinoma.

Adult↗
PubMed1998

Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.

PURPOSE: The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU. DESIGN: Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators. RESULTS: Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)). CONCLUSION: 5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.

Antimetabolites, Antineoplastic↗
PubMed1998

Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial.

PURPOSE: The aim of the study was to evaluate the efficacy of antiandrogen therapy on overall survival and response in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 244 patients with unresectable HCC were included in this multicentric double-blind trial. According to a two-by-two factorial design, patients were randomly assigned to receive one of the following treatments: pure antiandrogen plus placebo (A+P group, 60 patients); luteinizing hormone-releasing hormone (LHRH) agonist plus placebo (LHRH+P group, 62 patients); pure antiandrogen plus LHRH agonist (A+LHRH group, 62 patients); or placebo plus placebo (P+P group, 60 patients). Pure antiandrogen consisted of Anandron (Roussel-Uclaf Laboratory, Romainville, France) administered orally (300 mg daily for 1 month, then 150 mg daily). LHRH consisted of goseriline acetate (3.6 mg) or triptoreline (3.75 mg) administered monthly by subcutaneous injection. Treatment was given until death. Response was evaluated every 8 weeks according to World Health Organization (WHO) criteria. RESULTS: Six patients were considered ineligible. One patient had a complete response (A+P arm) and three had a partial response (two in the LHRH+P arm and one in the A+LHRH arm). An overall log-rank test did not demonstrate any significant difference in survival among the four arms. Taking the factorial design into account, comparison of survival showed no significant difference between Anandron-containing regimens and others, or between LHRH-containing regimens and others. No serious side effects occurred for any regimen. CONCLUSION: This controlled study shows clearly the lack of efficacy of androgen treatment in unresectable HCC.

Androgen Antagonists↗
PubMed1998

Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers.

PURPOSE: To evaluate the objective tumor response rate and safety profile of oxaliplatin when administered to patients with previously untreated metastatic colorectal adenocarcinoma. PATIENTS AND METHODS: A total of 39 patients were entered onto this phase II trial. One patient was excluded for having had a second cancer, so the study was based on 38 patients. Patients were treated with oxaliplatin 130 mg/m2 as a 2-hour infusion on day 1, every 21 days. Patients were assessed for response every three courses. All clinical and radiologic data were reviewed by an external panel of experts, with their assessment being considered definitive. RESULTS: Nine partial responses (PRs) were observed (response rate, 24.3%; 95% confidence interval, 11.8% to 41.2%). The median duration of response was 216+ days. Fifteen patients (40.5%) had stable disease and 13 (35.2%) had progressive disease. The median progression-free survival time for all patients was 126+ days (range, 21 to 447+). The main toxicity was peripheral sensory neuropathy. Grade 3 neurotoxicity (National Cancer Institute common toxicity criteria [NCI-CTC]) was reported in 13%. Hematologic and gastrointestinal toxicities were mild. The incidence of grade 3 neutropenia was 5.2%, while that of grade 3 or 4 thrombopenia was 7.9%. Vomiting (grade 3 or 4) occurred in 7.9% of patients and grade 3 diarrhea in 2.6%. CONCLUSION: This phase II study provides clear evidence of the safety and efficacy of oxaliplatin monotherapy at this dose and schedule in patients with previously untreated metastatic colorectal carcinoma.

Adenocarcinoma↗
PubMed1998

Clinical efficacy of oxaliplatin monotherapy: phase II trials in advanced colorectal cancer.

For the past 40 years, the mainstay of chemotherapy against colorectal cancer has been 5-fluorouracil (5-FU), often administered in recent years with folinic acid modulation. Traditional platinum derivatives have generally been ineffective in colorectal cancer therapy; however, the third-generation 1,2-diaminocyclohexane-platinum derivative oxaliplatin has shown good antitumor activity and a lack of cross-reactivity with cisplatin. Oddly, oxaliplatin was first developed as a combination therapy with 5-FU plus folinic acid administered as a chronomodulated infusion over 5 days. In subsequent phase II clinical trials, the activity of single-agent oxaliplatin was assessed in 63 previously untreated patients and 139 patients with metastatic disease refractory to 5-FU. In first-line therapy, the median overall survival was approximately 13 to 14 months, whereas in previously treated patients no longer responding to 5-FU, it was 8 to 10 months. The 18% objective response rate obtained with first-line therapy confirms that the activity of single-agent oxaliplatin is comparable to other anticancer therapies considered active against colorectal cancer. The 10% response rate obtained in second-line therapy in patients refractory to 5-FU provides a means for palliative care and suggests the possibility for a potentially active combination regimen with 5-FU.

Antineoplastic Agents↗
PubMed1998

[Importance of a multidisciplinary approach to metastatic cancer of the rectum].

Management of rectal cancers with synchronous metastasis is difficult. We evaluated in 23 patients a combination of pelvic radiotherapy at the dose of 45 Gy in 5 weeks and 25 fractions with chemotherapy by 5-fluorouracil (350 mg/m2/day) and folinic acid (20 mg/m2/day) for 5 days at the time of the first and the fifth week of the irradiation. Surgery was indicated firstly in cases of stricture or secondarily for resection of the primary location and, when possible, of the metastasis. General state of health of the patients improved in 35%, symptomatology in 86% and comfort in 72% of the cases. Response rates for the primary tumor were 41% of partial response and 50% of stable disease. For the metastatic lesions, they were 9% and 59% respectively. Sixty-one per cent of patients were secondarily operated with resection of the primary tumor in 12 cases and of hepatic metastases in 2 cases. The median survival and the median survival without progression were respectively 13 and 9 months. Radiochemotherapy combination as the first treatment was beneficial in 4/5 of the patients presenting a rectal cancer with synchronous metastasis and allowed us to select those that would secondarily benefit from a surgical resection.

Adult↗
PubMed1997

Accelerated fractionation in esophageal cancers: a multivariate analysis on 88 patients.

PURPOSE: Accelerated fractionation was used to shorten overall treatment time to increase locoregional control and cause-specific survival. METHODS AND MATERIALS: Eighty-eight patients with cancer of the esophagus ineligible for surgery were entered in the study between 1986 and 1993. Neoadjuvant chemotherapy was given to 64% of patients. Accelerated radiotherapy using the concomitant boost technique delivered a median dose of 65 Gy in a median overall treatment time of 32 days. RESULTS: The 3-year actuarial local control rate in patients with T1, T2, and T3 tumors was 71%, 42%, and 33%, respectively. The 3-year cause-specific survival rates were 40%, 22%, and 6%, respectively. Sixteen percent of patients experienced Grade 3 esophagitis. Late toxicity included esophageal stenosis and pulmonary fibrosis in 8% and 9% of the patients, respectively. Multivariate analysis demonstrated that T stage and overall treatment time were prognostic factors for cause-specific survival. T stage and neoadjuvant chemotherapy were independent prognostic factors for locoregional control. CONCLUSION: These findings suggest that accelerated fractionation given in an overall treatment time of <35 days might be beneficial for early-stage cancer of the esophagus. Neoadjuvant chemotherapy is not recommended, as it was a significant adverse prognostic factor in the multivariate analysis for local control. Accelerated fractionation can be carried out with moderate acute and late toxicity.

Adenocarcinoma↗
PubMed1997

[Judgement criteria in treatments of advanced colorectal cancers and methods of evaluation].

Because of their bad prognosis, the effectiveness assessment of advanced cancer therapy is particularly important. A strict measurement of the treatment's benefit is necessary in order to consider its true interest objectively. The assessment of the tumor response allow an appreciation of the immediate effectiveness of the treatment on the lesions. An objective response doesn't mean that there is a survival improvement, which remains the primary aim of all treatments. Statistical methods are used so as to estimate overall survival or relapse-free arrival. Evaluating the quality of life is now essential in advanced cancer management. This is a complex, subjective and multi-dimensional concept and its evaluation requires some specific and validated instruments.

Clinical Trials as Topic↗
PubMed1997

Economic implications of hepatic arterial infusion chemotherapy in treatment of nonresectable colorectal liver metastases. Meta-Analysis Group in Cancer.

BACKGROUND: Approximately 20% of patients with colorectal cancer die of metastases confined to the liver. A meta-analysis recently performed by our group confirmed that in these patients hepatic arterial infusion of 5-fluoro-2'-deoxyuridine, compared with intravenous chemotherapy with fluoropyrimidines or supportive care (including symptom palliation when necessary), improved tumor response. PURPOSE: Because of the high cost of hepatic arterial infusion, we undertook a cost-effectiveness analysis that related the cost of such therapy to its medical efficacy. METHODS: The patient population was drawn from the seven randomized clinical trials included in the meta-analysis and included individual data on 654 patients. Of these seven trials, five compared hepatic arterial infusion and intravenous chemotherapy and two compared hepatic arterial infusion and a control group in which some patients could be left untreated. Patients assigned to receive hepatic arterial infusion made up the hepatic arterial infusion group; the other patients constituted the control group. The measures of efficacy were survival and tumor response. Health-care costs (in 1995 U.S. dollars) were computed over the duration of patient follow-up and were derived from actual costs in two centers, one at Henri Mondor Hospital (Paris, France) and the other at Stanford University Medical Center (Palo Alto, CA). The total cost of treatment included the initial procedure, chemotherapy cycles, and main complications. RESULTS: The mean gain in life expectancy in the hepatic arterial infusion group compared with the control group was 3.2 months (standard error = 1.0 month). For patients treated by hepatic arterial infusion in Paris, the hepatic arterial infusion pump, initial hospitalization, and the entire process (including follow-up and complications) cost, on average, $8400, $15172, and $29562, respectively; in Palo Alto, these costs were $4700, $13784, and $25 208, respectively. For patients in the control groups in Paris and Palo Alto, the total treatment costs were, on average, $9926 and $5928. The additional costs of hepatic arterial infusion over control treatment were $19636 in Paris and $19280 in Palo Alto. The cost-effectiveness (i.e., the additional cost divided by the additional benefit) with respect to survival of the patients in the hepatic arterial infusion group compared with the patients in the control group was $73635 per life-year in Paris and $72300 per life-year in Palo Alto. CONCLUSIONS AND IMPLICATIONS: The cost-effectiveness of localized chemotherapy for colorectal liver metastases is within the range of accepted treatments for serious medical conditions, although it might be considered borderline by policy-makers in some countries. Prospective clinical trials should be conducted to more definitively answer this question.

Antimetabolites, Antineoplastic↗
PubMed1997

Abdominoperineal resection combined with pre- and postoperative radiation therapy in the treatment of low-lying rectal carcinoma.

PURPOSE: A series of patients with rectal carcinoma irradiated by a sandwich technique combined with surgery is retrospectively analyzed. METHODS AND MATERIALS: From 1978 to 1991, 155 patients with low or mid rectal carcinoma received abdominoperineal resection combined with a preoperative irradiation regimen of 35 Gy delivered in 14 fractions of 2.5 Gy each over a period of 3.5 weeks. The dose was increased to 45 Gy in the case of tumor fixation. According to histopathological findings, this irradiation was complemented in 87 cases by a postoperative dose of 25 Gy delivered in 10 fractions, for a total dose of 60 Gy delivered in the posterior pelvis. RESULTS: Five-year survival was 66.8% for the entire population. The 5-year actuarial local control rate was 77.6%. Carcinologic results and toxicity were analyzed according to the pathological findings and the modalities of radiation therapy. CONCLUSIONS: The postoperative boost after a preoperative moderate dose of irradiation seems to have no utility. Thus, this sandwich technique is not recommended.

Adult↗
PubMed1997

Correlation between antiretroviral resistance mutations, biological parameters, and clinical evolution in zidovudine-treated patients infected with human immunodeficiency virus type 1.

To evaluate the correlation between zidovudine (ZDV) resistance mutations of human immunodeficiency virus type 1 (HIV-1), biological parameters, and clinical evolution, 111 HIV-1-infected patients treated with ZDV were studied. Specific mutations at codons 70, 215, and 41 in the HIV-1 reverse transcriptase coding region conferring resistance to ZDV were detected using a selective polymerase chain reaction. The appearance of ZDV resistance mutations was significantly correlated with baseline clinical stage, CD4+ cell count, and viral load, but not with duration of ZDV therapy or p24 antigen level. In univariate analysis, results showed a prognostic role of mutations at codons 215 and 41 for clinical progression to the acquired immune deficiency syndrome (AIDS) or death. In multivariate analysis after controlling for viral load, CD4+ cell count, and clinical stage, the presence of the mutation at codon 215 (but not at codon 41) remained an independent predictor of subsequent clinical evolution.

Adult↗
PubMed1997

Simultaneous high-dose external irradiation and daily cisplatin in unresectable, non-metastatic adenocarcinoma of the pancreas: a phase I-II study.

BACKGROUND AND PURPOSE: Clinical trials have demonstrated that high dose radiation therapy and daily cisplatin (CDDP) could increase local control and survival in carcinoma from various sites. The present phase I-II study has combined high dose radiation therapy and daily CDDP at escalating dosages. METHODS: From August 1994 to December 1995, 23 patients with non-resectable carcinoma of the pancreas were enrolled in a phase I-II multicentric, pilot study to test the toxicity and the effectiveness of high dose radiotherapy and daily cisplatin (CDDP) at escalating dosages. A dose of 6 mg/sqm/day of CDDP was selected for the phase II step since no grade IV toxicity occurred in any patient in the phase I step. RESULTS: Toxicity was considered fairly acceptable. At the time of analysis, the 23 patients who entered the study had clear evidence of evolutive disease either locally or distantly in the liver. It is suggested that high dose radiotherapy (60 Gy continuously) and daily CDDP have little effect on local control of the tumor and survival, and only a moderate effect on pain. CONCLUSIONS: In unresectable, apparently non-metastatic cancers of the pancreas, there is an urgent need for new agents or new combinations of agents to be tested.

Adenocarcinoma↗
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↗