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Gercor : Abstracts ASCO 2004
Gercor : Abstracts ASCO 2003
Gercor : Abstracts ASCO 2002
 

 


Abstract 525 : Oxaliplatin/5-FU/LV in adjuvant colon cancer: safety results of the international randomized MOSAIC trial.

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Aimery de Gramont, Corrado Boni, Mathilde Navarro, Josep Tabernero, Tamas Hickish, Clare Topham, Andrea Bonetti, Philip Clingan, Neville Davidson, Lamia Mounedji-Boudiaf, Thierry Andre, Hopital Saint-Antoine, Paris, France; Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; Hospital Duran i Reynals, Llobregat, Spain; Hospital Vall d'Hebron, Barcelona, Spain; Royal Bournemouth Hospital, Bournmouth, UK; St Luke's Cancer Center, Royal Surrey County Hospital, Guildford, UK; Ospedale di Legnago, Legnago, Italy; Illawara Cancer Care Center, Wollongong, Australia; North Middlesex Hospital, London, UK; Sanofi-Synthelabo, Paris, France; Hopital Tenon, Paris, France.

MOSAIC trial was built upon the assumption that the increase in progression free survival observed with FOLFOX in first line advanced colorectal cancer (de Gramont, JCO2000) should translate into improvement in Disease Free Survival (DFS) of patients with early stage disease. Patients with completely resected stage II/III colon cancer were stratified according to study center, stage and randomly assigned to receive LV5FU2 (leucovorin 200mg/m2 as a 2-hour infusion, 5-FU 400mg/m2 bolus and 600mg/m2 22-hour continuous infusion, d1-2) or FOLFOX (LV5FU2 + oxaliplatin 85mg/m2 d1) bimonthly for 12 cycles (Cy). 2248 patients (1124 each arm) were randomized between 10/1998 and 1/2001 in 147 centers. All completed treatment. Patients characteristics at baseline were (Control(C) / FOLFOX(F)): Male(%) 52/56, mean age 58.7/59, stage II/III(%) 40/60 in each arm. 12150 cycles were administered in C and 11461 in F. Oxaliplatin and 5FU relative dose intensities were over 80%. Incidence of NCI G3-4 toxicities in C/F are (%pt): vomiting 1/6, diarrhea 6/11, mucositis 2/3, allergy <1/2, thrombocytopenia <1/2, neutropenia %pt (%cy): 4.6 (0.5)/40 (6.6) with <1/1.8 febrile neutropenia. G3 neurotoxicity was observed in 12% of patients with an 18% probability up to a cumulative dose of 1000mg/m2. 58 % of patients improved/recovered within one month after treatment discontinuation. All cause mortality under treatment was: 6(0.5%)/6(0.5%) including 3 deaths per arm in the first 2 months. These results show that FOLFOX is feasible and safe in the adjuvant treatment of colon cancer. Final dosing and safety results including mature data on neurotoxicity reversibility will be presented during the meeting. Follow-up is ongoing to assess oxaliplatin benefit on DFS and survival.

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Abstract 529 : Phase III trial (Gercor C96.1) comparing bimonthly LV5FU2 to monthly 5FU-leucoverin high dose (LV hd) in patients with Dukes B2 and C colon cancer.

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Thierry Andre, Philippe Colin, Christophe Louvet, Erik Gamelin, Olivier Bouche, Emmanuel Achille, Nicolas Colbert, Catherine Boaziz, Pascal Piedbois, Nicole Tubiana-Mathieu, Arnauld Boutan-Laroze, Michel Flesch, Keltoum Berkani, Marc Buyse, Aimery de Gramont, Hopital Tenon, Paris, France; Policlinique de Courlancy, Reims, France; Hopital St-Antoine, Paris, France; Centre Paul Papin, Angers, France; CHU de Reims, Reims, France; Clinique de l'Orangerie, Strasbourg, France; Hopital St-Joseph, Paris, France; Centre Paris Nord, Sarcelles, France; Hopital Henri Mondor, Paris, France; CHU de Limoges, Limoges, France; Centre Hospitalier d'Argenteuil, Argenteuil, France; Hopital Devron, Dijon, France; IDDI, Sartrouville, France; IDDI, Brussels, Belgium.

LV5FU2 was less toxic and more efficient (response rate and PFS) than 5FU-LV low dose in advanced colo-rectal cancer [J Clin Oncol 15:808-15, 1997]. Between 7/96 and 11/99, 905 patients with Dukes B2 (43%) and C (57%) colon cancer were enrolled. A double randomization (2x2 factorial design) was used to allocate patients to either 24 or 36 weeks of either monthly 5FU-LV hd (d,L-LV 200 mg/m2 or L-LV 100 mg/m2 15 min iv infusion followed by 5FU 400 mg/m2 15 min iv infusion, d1-5 q4 wk) or LV5FU2 (d,L-LV 200 mg/m2 or L-LV 100 mg/m2 2-hour infusion followed by iv bolus infusion 5FU 400 mg/m2 and 22 hours continuous infusion 600 mg/m2, d1 and d2 q2 wk). Form L-LV was administered to 60% of patients and d,L-LV to 40% of patients. Important prognostic characteristics were well balanced between the randomized groups. The proportion of any grade III-IV toxicity was 27% for 5FU-LV hd and 11% for LV5FU2 on a per patient basis (p less than 0.001) and 19% for 5FU-LV hd and 8% for LV5FU2 on a per cycle basis (p less than 0.0001). The median follow-up time was 35 months in both groups. There were no statistically significant differences between 5FU-LV hd and LV5FU2 in terms of disease free survival (119 vs 121 events, hazard ratio=1.05, p=0.7) nor between 24 or 36 weeks of therapy (120 vs 120 events, hazard ratio=0.98, p=0.85). Preliminary survival comparisons will be presented at the meeting. We conclude that bi-monthly LV5FU2 is less toxic, and as effective as, 5FU-LV hd. Because of this low toxicity, LV5FU2 is currently evaluated in the adjuvant setting in combination with oxaliplatin or CPT11.

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Abstract 658 : Leucovorin, 5-fluorouracil infusion and irinotecan (FOLFIRI-3) in pretreated patients with metastatic colorectal cancer.

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Frederique Maindrault, Christophe Louvet, Christophe Tournigand, Honorine Gervais, May Mabro, Pascal Artru, Marie-Line Garcia, Thierry Andre, Elisabeth Carola, Aimery de Gramont, Hopital St-Antoine, Paris, France; Hopital Tenon, Paris, France; Hopital de Senlis, Senlis, France.

FOLFIRI-1 with irinotecan 180mg/sqm on day 1 has shown a good efficacy in first-line therapy but little activity in patients with advanced colorectal cancer resistant to leucovorin (LV), fluorouracil (5FU) and oxaliplatin: partial response 4%, stable disease 35%, median progression-free survival 2,5 months (Tournigand, ASCO 2001 #494). Synergy between 5FU and irinotecan has been found either with irinotecan given before or given after 5FU. FOLFIRI-3 regimen was designed to use both. FOLFIRI-3 consisted of LV 400 mg/sqm as a 2-h infusion on Day 1 followed by 46-h continuous infusion of 5-FU 2,000 mg/sqm, and CPT-11 100 mg/sqm as a 60-min infusion on Day 1, repeated on day 3, every 2 weeks. Twenty-two patients(11M/11F, median age 61 years) who previously received LV-5FU-oxaliplatin (FOLFOX) were included. Twenty patients were evaluated as of November 2001: partial response 4 patients (20%), stable disease 11 patients (55%), 5 progression (25%). From the start of FOLFIRI-3, median progression-free survival was 6.7 months. Only 7 patients (35%) had Grade 3/4 NCI-CTC toxicities: neutropenia 30% (febrile 5%), diarrhea 15%, mucositis 5%, mucositis 5%. 55% of the patients had grade 2 alopecia. FOLFIRI-3 is a promising regimen in pretreated patients with 75% of ORR plus SD, translated into prolonged progression-free survival. This regimen is now further evaluated in a multicenter study conducted by the Gercor.

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Abstract 672 : FOLFOX7 / FOLFIRI (MIROX) regimen as (neo)adjuvant chemotherapy for patients with resectable metastatic colorectal cancer : preliminary results

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Pascal Artru, Julien Taieb, Christophe Tournigand, Christophe Louvet, Samira Hafraoui, Francois Paye, Frederique Maindrault, Rolland Parc, Brice Gayet, Jean-Luc Molitor, Aimery de Gramont, Hopital St-Antoine, Paris, France; Inst Mutualiste Montsouris, Paris, France.

Between sept. 99 and sept. 01, 48 patients (pts) with resectable metastatic colorectal adenocarcinoma were prospectively included in this study. MIROX regimen consisted in six cycles of FOLFOX 7 (FA 400 mg/sqm, Oxaliplatin 130 mg/sqm in 2h infusion and 5-FU 46h-infusion 2400 mg/sqm every two weeks), followed by six cycles of FOLFIRI (same 5FU/LV regimen with CPT11 180 mg/sqm in 90 min infusion). Surgery was performed before chemotherapy (26 pts) or after the 6 cycles of FOLFOX7 (22 pts), 6 cycles of FOLFIRI being administered thereafter. Characteristics of the pts and the tumors were M/F : 30/18; mean age: 57 yrs, range 35-77; primary tumor colon/rectum : 34/14; resected metastatic sites : liver (n=38 pts), lung (5), peritoneum (5), and other (5); synchronous metastases : 29, metachronous : 19 (median time from primary tumor : 19 months). Grade 3-4 NCI-CTC toxicities per patient for FOLFOX7 / FOLFIRI were neutropenia 21% / 28.6%, thrombocytopenia 34.2% / 0%, nausea-vomiting 7.9% / 0%; diarrhea 13.2% / 0%; grade 2 alopecia 0% /39.3%; grade 2 (specific scale) neuropathy 52.6% / 0% (no grade 3 neuropathy). No toxic death occurred. For pts treated with FOLFOX7 before surgery, objective response rate (WHO criteria) was 80% (13% complete response); all but one underwent surgery; two pts refused post-operative chemotherapy. With a median follow-up of one year, all pts are still alive. Relapse occurred in 12 pts, with a median time from the surgery of 10.5 months; relapses were in the same site that was resected for 5 pts, or in another site for 7. The MIROX regimen is feasible and well tolerated in pts with resectable metastatic colorectal cancer. A longer follow-up is needed to assess the efficacy. This regimen will soon enter in a phase III study conducted by the Gercor. Updated data will be presented during the meeting.

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Abstract 688 : Reintroduction of irinotecan in pretreated patients with metastatic colorectal cancer

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Honorine Gervais, Pascal Artru, Christophe Louvet, Christophe Tournigand, Frederique Maindrault, Marie-Line Garcia, Aimery de Gramont, Hopital St-Antoine, Paris, France.

Based on the promising preliminary results of the FOLFIRI-3 regimen in patients resistant to the FOLFOX regimen, we evaluated this new regimen in patients previously treated with irinotecan in combination either with 5FU (FOLFIRI-1 regimen) or with ZD9331, and also with FOLFOX. FOLFIRI-3 consisted of LV 400 mg/sqm as a 2-h infusion on Day 1 followed by 46-h continuous infusion of 5-FU 2,000 mg/sqm, and CPT-11 100 mg/sqm as a 60-min infusion on Day 1, repeated on day 3, every 2 weeks. 19 patients (12M/7F, median age 60 years) who previously received irinotecan-based regimen and FOLFOX regimen and had documented disease progression were included. 16 patients were evaluated as of November 2001: partial response 3 patients (19%), stable disease 9 patients (56%), 4 progression (25%). 6 out of 7 patients who did not demonstrated progression during the first administration of irinotecan achieved PR or stable disease. 6 out of 9 patients who had progression on the first irinotecan-based therapy had PR (1pt) or stable disease. The patient who had PR had failed on the FOLFIRI-1 regimen. From the start of FOLFIRI-3, median progression-free survival was 4.1 months. 8 patients (50%) had Grade 3/4 NCI-CTC toxicities: neutropenia 19%, diarrhea 6%, mucositis 6%, nausea 6%. 62% of the patients had grade 2 alopecia. Reintroduction of irinotecan in the FOLFIRI-3 regimen can achieve disease control, even in some patients resistant to FOLFIRI-1 regimen.

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Abstract 883 : Consolidation intraperitoneal chemotherapy (IP) in advanced ovarian cancer (AOC) with pathological complete response (pCR) or with microscopical residual disease. A Gercor study.

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Christophe Tournigand, Christophe Louvet, Jean-Luc Molitor, Nidal Dehni, Alain Sezeur, Alain Pigne, Loic Marpeau, Jean Cady, Veronique Lejeune, Marie-Line Garcia, Aimery de Gramont, Hopital Saint-Antoine, Paris, France; Hopital des Diaconnesses, Paris, France; Clinique Geoffroy St-Hilaire, Paris, France; Hopital Charles Nicolle, Rouen, France.

IP in AOC demonstrated significant activity in patients with small-volume residual disease (RD), as part of the initial chemotherapy or after failure of IV CT. However, long term evaluation is seldom reported. We report our results with consolidation IP CT in 68 patients who achieved a complete pathological response after IV CT. Survival was compared to that of a group of 21 contemporaneous pts treated with IP, who had microscopical RD before IP. All the pts had an AOC (stage III-IV, under 70 yr.) who entered in four prospective trials (1984-1997) including IV CT based on cisplatin (6 cycles) and anthracyclines, early debulking surgery after three cycles of CT in case of initial RD over 2 cm, second-look laparotomy (SLL) and intraperitoneal consolidation CT (Proc ASCO; 10:639, 1991; Proc ASCO; 12:888, 1993; Eur J Cancer; 28:53, 1992). Among 219 pts, 68 with biopsy negative second-look laparotomy received every 4 weeks 3 consolidation cycles of IP CT via a totally implantable port. 21 pts out of 219 had microscopic residual disease at SLL and were treated with 6 cycles of IP. IP chemotherapy consisted in mitoxantrone 25 mg/sqm D 1, VP16 120 mg/sqm D 1 and cisplatin 100 mg/sqm (if no previous neuropathy). Characteristics of pCR and microscopic patients were respectively : mean age 56 vs 54 years, stage III 93% vs 95%, initial RD over 2cm 27% vs 31%, initial RD=0 19% vs 14%, performance status (PS) 0 46% vs 48%, PS1 40% vs 43%. With a median follow-up of the study of 8.25 years, median overall survival was 69 months in the pCR group vs 49 months in the microscopic group (p=0.06). Progression-free survival was 34 months in the pCR group and 16 months in the microscopic group (p=0.0026). Relapse involved peritoneum in 31% and 67% of the pts. Consolidation IP chemotherapy in patients with pCR resulted in an increase PFS and a lower rate of peritoneal relapse compared to a group of patients with microscopical RD at initiation of IP.

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