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British Journal of Surgery 04/2012; 99(4):558-65. · 4.61 Impact Factor
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M Ychou,
J-L Raoul,
J-Y Douillard,
S Gourgou-Bourgade,
R Bugat,
L Mineur,
F Viret, Y Becouarn,
O Bouché,
E Gamelin,
M Ducreux,
T Conroy,
J-F Seitz,
L Bedenne,
A Kramar
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ABSTRACT: This multicenter adjuvant phase III trial evaluated the addition of irinotecan to LV5FU2 in colon cancer patients at high risk of relapse.
A total of 400 patients with histologically proven primary colon cancer with postoperative N1 detected by occlusion/perforation or N2 were randomised to: A-LV5FU2 [leucovorin 200 mg/m(2), 2-h infusion, 5-fluorouracil (5-FU) 400 mg/m(2) bolus, 600 mg/m(2) 22-h continuous infusion, days 1 and 2] or B-LV5FU2 + IRI (irinotecan 180 mg/m(2) 90-min infusion day 1 + LV5FU2) fortnightly for 12 cycles. Primary end point was disease-free survival (DFS).
Median follow-up was 63 months. Significantly more T4 tumours and 15 or more positive lymph nodes were observed in arm B. 5-FU relative dose intensity (RDI) was >0.80 for 94% and 77% in arms A and B, respectively (P < 0.001). Irinotecan RDI was >0.80 for 70% patients. There were more grades 3 and 4 neutropenia in arm B (4% versus 28%, P < 0.001). The 3-year DFS was 60% [95% confidence interval (CI) 53% to 66%] and 51% (95% CI 44% to 58) in arms A and B, respectively. No difference was observed [hazard ratio (HR) = 1.12, 95% CI 0.85-1.47, P = 0.42] even when adjusted for prognostic factors (adjusted HR = 0.98, 95% CI 0.74-1.31, P = 0.92). The 5-year overall survival (OS) was 67% (95% CI 59% to 73%) and 61% (95% CI 53% to 67%) in arms A and B, respectively.
Adjuvant LV5FU2 + IRI compared with LV5FU2 alone in patients at high risk of relapse showed no improvement in DFS and OS.
Annals of Oncology 01/2009; 20(4):674-80. · 6.43 Impact Factor
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ABSTRACT: Intraoperative use of radiofrequency ablation (IRFA) to treat liver metastases is controversial. The aim of this study was to compare local recurrence rate and survival after IRFA versus resection.
Three groups from 99 patients were consecutively operated on for 307 liver metastases with 2years of follow up: group 1, IRFA alone (n=34); group 2, IRFA plus resection (n=28); group 3, resection alone (n=37). The choice of IRFA or resection was made on the basis of the sizes and topographies of the metastases with the goal of achieving R0 treatment.
Mortality was zero; morbidity was 9%, 11% and 11% in the three groups respectively. Median follow-up after surgery was 30months. Total hepatic recurrences occurred in 59 (60%) patients. Median survival without hepatic recurrence was 17months with no difference between the three groups (P=0.474). Total local recurrence occurred in 4 (12%) patients in group 1, in 2 (8%) patients in group 2, and in 2 (6%) patients in group 3. Survival at 2years was no different in the three groups.
Assessing IRFA indications by size and the topographical characteristics of the liver metastases yields identical local recurrence rates to resection after 2years of follow up.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 03/2008; 34(2):185-90. · 2.56 Impact Factor
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ABSTRACT: Radiofrequency ablation (RFA) has a role in the treatment of unresectable liver metastases either percutaneously or in open surgery. The aim of this study was to determine the feasibility and value using RFA, resection or in combination to cure liver metastases of colorectal or other origin.
Fifty-two consecutive patients were operated on with the intention to treat their liver metastases using both techniques of RFA and resection in the same curative intent. A CT scan was performed 2 months postoperatively and then every 4 months.
Fifty patients with 137 metastases could be treated: 55 lesions were resected and 82 were ablated. Curative treatment of 13 patients could only be achieved by using RFA combined with resection. Morbidity was 16% and local treatment proved insufficient in three cases. Estimated 1-year survival probabilities were, respectively, 0.85 in the colorectal group and 0.80 in the non-colorectal group.
RFA increased resectability of liver metastases and reduced the morbidity. Respective indications of both techniques were complementary and depend on the size and the topography of the lesion to be treated.
European Journal of Surgical Oncology 06/2004; 30(4):399-406. · 2.50 Impact Factor
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J-F Seitz,
J Bennouna,
B Paillot,
E Gamelin,
E François,
T Conroy,
J-L Raoul, Y Becouarn,
F Bertheault-Cvitkovic,
M Ychou,
S Nasca,
A Fandi,
P Barthelemy,
J-Y Douillard
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ABSTRACT: This multicenter, phase II, open-label study evaluated the antitumor efficacy and safety of oxaliplatin and raltitrexed (Tomudex) in non-pretreated advanced colorectal cancer patients.
Seventy-one patients received oxaliplatin 130 mg/m(2) and raltitrexed 3 mg/m(2) intravenously on an outpatient basis every 3 weeks. All patients had histologically proven metastatic colorectal adenocarcinoma, performance status <or=2 and good baseline organ function. Most (56%) had only one disease site. All patients were assessed for safety, and 66 of 69 eligible patients were assessed for response.
A total of 404 cycles were administered, with a median of six cycles per patient (range 1-12 cycles). Relative dose intensities were 0.98 and 0.98 for oxaliplatin and raltitrexed, respectively. The most common grade 3-4 toxicities (National Cancer Institute Common Toxicity Criteria) among treated patients were as follows: neutropenia (21 patients, 30%), asthenia (eight, 11%), diarrhea (12, 17%), liver function test abnormalities (24, 34%), nausea (nine, 13%) and vomiting (nine, 13%). Two treatment-related deaths occurred (hematotoxicity in one patient and gastrointestinal toxicity in the other) and two further deaths were possibly related to treatment (hepatic dysfunction in one patient and neuropathy in the other). Thirty-seven objective responses (one complete) were obtained [objective response rate 54%; 95% confidence interval (CI) 42% to 65%] in eligible patients. The median response duration was 8.5 months (95% CI 6.7-12.2 months), while median progression-free and overall survival among eligible patients were 6.2 (95% CI 5.1-6.9 months) and 14.6 months (95% CI 11.0-18.9 months), respectively.
The present study confirms the feasibility of the raltitrexed plus oxaliplatin combination and its activity in non-pretreated advanced colorectal cancer patients.
Annals of Oncology 07/2002; 13(7):1072-9. · 6.43 Impact Factor
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ABSTRACT: After decades of exclusive use of fluorouracil in the treatment of metastatic colorectal cancer, three new drugs, among them oxaliplatin, have recently shown interesting results. Oxaliplatin has an activity when it is given alone but this drug is particularly interesting for combination chemotherapy because it has a favourable toxicity profile without important haematologic or digestive toxicities and because it has a convenient schedule of administration (short infusion every two or three weeks). Phases I and II studies have demonstrated the feasibility of the combination of raltitrexed and oxaliplatin. A recent phase II study has evaluated the efficacy of this new combination in 71 non pre-treated patients. The observed response rate was high: 59.5%. The combination of oxaliplatin and irinotecan has been assessed in three phase I studies (two with a three-weekly schedule and the last one with a biweekly schedule). These studies have determined the doses which could be used in further phase II studies, these doses were close to the doses used in monotherapy. Results of the efficacy of the three-weekly schedule are available only in second line therapy, with 42% of objective response rate in 36 patients. The dose intensity was maintained with the use of hematopoietic growth factors. These new combinations with oxaliplatin give us the opportunity to treat the patient with schedules excluding fluorouracil which has a variable metabolism.
Bulletin du cancer 09/2001; 88 Spec No:S35-9. · 0.67 Impact Factor
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Critical Reviews in Oncology/Hematology 11/1999; 32(2):145-54. · 4.41 Impact Factor
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ABSTRACT: New innovative cytotoxic agents have proven active for treating patients with metastatic cancer who have failed first line 5FU based therapy, with sizeable objective response rates and a much higher rate of stabilization. The benefit of stabilization has not yet been well evaluated. A prospective multicentric study was carried out with 80 patients treated by second line chemotherapy for metastatic colorectal cancer. Tumor assessment and symptomatic status were reported at each cycle with a 4-month follow-up, allowing dynamic patient categorization per health state associated with the treatment. It appears that patients who are stabilized by chemotherapy have a quality of life profile comparable to that of responders, as opposed to patients with progressive disease. More patients experience improvement or stabilization of their quality of life, while they are stabilized versus progressive patients. Average number of days in hospital and hospital costs are cut down by three during stabilization as opposed to progressive disease. These results provide evidence that disease stabilization brings benefit to patients and reduces hospitalization.
Bulletin du cancer 03/1999; 86(2):195-201. · 0.67 Impact Factor
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ABSTRACT: 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.
Seminars in Oncology 05/1998; 25(2 Suppl 5):23-31. · 3.50 Impact Factor
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P Rougier,
R Bugat,
J Y Douillard,
S Culine,
E Suc,
P Brunet, Y Becouarn,
M Ychou,
M Marty,
J M Extra, [......],
J F Seitz,
G Ganem,
M Namer,
T Conroy,
S Negrier,
Y Merrouche,
F Burki,
M Mousseau,
P Herait,
M Mahjoubi
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ABSTRACT: To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients.
Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function.
Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern.
CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.
Journal of Clinical Oncology 02/1997; 15(1):251-60. · 18.37 Impact Factor
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ABSTRACT: A 45 year-old patient presented with an epidermoid carcinoma of the tongue and cranial hypertension. MRI showed dural venous sinus occlusion, without infiltration or compression by a metastatic tumor. Anticoagulation led to recanalization of the occluded sinuses, as shown by the follow-up MRI, three months later. The pathophysiology of these rare paraneoplastic cerebral venous thrombosis is discussed.
Revue Neurologique 02/1993; 149(4):297-9. · 0.49 Impact Factor
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ABSTRACT: From april 1978 to december 1988, 24 patients were treated were by radiotherapy at the Bergonié Foundation cases were for ethmoidal cancer cases. Twenty two for initial treatment and two refermed for local recurrence. The mean age was 51.4 years and the sex ratio was 5.2 (21 men/4 women). Histologically there were 15 adenocarcinomas, 3 squamous carcinomas, 4 undifferentiated carcinomas and 2 esthesioneuroblastomas. According to the classification of the University of Florida, they were retrospectively classified as stage I = 9 pts, stage II = 5 and stage III = 10. Twenty one patients had postoperative radiotherapy and 3 had exclusive radiotherapy. The average dose was 55.3 Gy. Local control was obtained in 12 pts. Seven patients have recurred locally (within an average period of 12 months) and 5 patients showed progression of disease after treatment. The overall actuarial survival and the disease free survival at 5 years were respectively 50% and 53%. The actuarial survival by stage at 2 years and 5 years was: stage I (88% and 61%), stage II (100% and 50%), stage III (0%). The prognosis of ethmoidal cancer is strictly correlated to local control. For this reason, radiotherapy (with or without surgery) remains important in the treatment of this disease.
Annales de radiologie 02/1991; 34(4):221-5.
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ABSTRACT: Fifteen patients (median age 62, with a mean Karnofsky performance status of 70%) presenting with advanced colorectal carcinoma were included in the study. The treatment combination consisted of 5-fluorouracil (800 mg/m2 in a 30 min infusion, days 1 and 8), teniposide (80 mg/m2 in i.v. push, day 1), and mitomycin-C (10 mg/m2 in i.v. push, day 1); therapy was resumed every 29 days. A partial objective response (for 4 months) was noted in one patient who had received no prior chemotherapy; the overall median survival of the 15 patients was 5 months. Toxicity was acceptable, with leukopenia (1 case), mucositis (1 case) and diarrhea (1 case), leading to drug dose reduction. Chemotherapy was stopped once owing to severe hematologic toxicity. With the doses and schedule used, the drug combination appears to have minimal activity in advanced colorectal cancer.
Tumori 03/1988; 74(1):75-7. · 0.86 Impact Factor
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ABSTRACT: Fifteen patients, median age 64 years, presenting with advanced gastrointestinal adenocarcinomas, were included in this study. The treatment combination consisted of folinic acid (200 mg/m2, IV bolus injection) followed by 5-fluorouracil (5-FU; 400 mg/m2, 30-min infusion) for 5 consecutive days and mitomycin C (10 mg/m2, IV bolus injection) on day 1, the therapy being resumed every 21 days. An objective response was noted in 7 of 15 patients (47%): 1 complete and 6 partial responses, including 4 of 5 patients who had received no prior chemotherapy and 3 of 10 patients who previously failed to respond to 5-FU. Objective responses were encountered in 4 of 7 stomach cancers, 2 of 3 pancreas tumors, and in only 1 of 5 colorectal carcinomas. Furthermore, 9 of 11 patients were completely relieved of their abdominal pain. The median duration of remission was 5 months. The median survival time of patients who responded to treatment was 7 months. Toxicity was acceptable, with mainly leukopenia and/or thrombocytopenia (5 patients) and oral mucositis (3 patients), leading to dose reduction. The combination of 5-FU+ folinic acid + mitomycin C appears to be a potentially effective regimen in the treatment of advanced gastrointestinal tumors, even in patients previously treated with 5-FU.
Oncology 02/1988; 45(4):269-72. · 2.27 Impact Factor
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Annales de Chirurgie 02/1988; 42(1):22-7. · 0.35 Impact Factor
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ABSTRACT: Twenty-five adult patients, 15 men and 10 women, with a median age of 49, and presenting with metastatic or locally advanced soft tissue sarcomas, have been treated with chemotherapy protocol combining cisplatinum, 100 mg/m2, vindesine, 4 mg/m2, and either adriamycin, 50 mg/m2 (APEL) (16 patients), or epirubicin, 100 mg/m2 (EPEL) (9 patients). The overall toxicity was high, with hematologic, digestive and renal side effects, leading to stop the treatment in 5/25 patients, and to reduce drugs dosage by greater than or equal to 25% in nearly half of the patients. A tumor response (tumor regression of greater than or equal to 50%) was observed in 9/25 patients (36%), including one histologically confirmed complete regression. Among 16 patients presenting with pain, a complete relief was obtained in 7. Thus, APEL/EPEL produced a response rate which compared with that obtained with CYVADIC regimen, but the toxicity of these regimens was higher leading us to stop these protocols. Others associations should be developed. In that regards, epirubicin may be considered as doses as high as 100 mg/m2, was tolerated as 50 mg/m2 of adriamycin, and produced a response in 5 over 9 patients treated.
Bulletin du cancer 02/1987; 74(2):109-16. · 0.67 Impact Factor
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La Presse Médicale 11/1986; 15(33):1684. · 0.67 Impact Factor
