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Thierry André

Publications and source records attributed to Thierry André.

At least 19 recordsLinked to original sources
PubMed2006

Current issues in adjuvant treatment of stage II colon cancer.

BACKGROUND: Adjuvant chemotherapy with 5-fluorouracil modulated by folinic acid, combined with oxaliplatin, has now become an accepted standard of care for patients with stage III colon cancer. In contrast, the use of adjuvant therapy for stage II patients remains controversial, and the identification of reliable prognostic factors to aid therapeutic decision making is crucial. METHODS: The authors critically review the results of clinical trials and meta-analyses investigating the value of adjuvant chemotherapy for stage II patients, emphasizing the heterogeneous nature of this population and the difficulty of performing clinical trials with sufficient power to reliably assess treatment efficacy. They also discuss the evidence concerning potential prognostic factors, particularly molecular markers. RESULTS: Available clinical trial data do not support the routine use of adjuvant chemotherapy for all stage II patients but suggest that it should be considered, particularly for certain high-risk patients. Recent guidelines advocate considering factors such as tumor differentiation, tumor perforation, number of lymph nodes examined, and T stage when assessing the likely benefit:risk ratio. Microsatellite instability and allelic imbalance seem to be strong predictors of good and poor prognosis, respectively, and in the near future, therapeutic decision-making models are likely to be further refined by the inclusion of such molecular markers. CONCLUSIONS: There is growing evidence that the prognosis of certain stage II patients with unfavorable prognostic factors can be improved by adjuvant chemotherapy, and increasingly refined tools are now available to define those most likely to benefit. Referral of stage II patients for individual assessment is strongly recommended.

Allelic Imbalance↗
PubMed2006

[Adjuvant treatment of colon cancer MOSAIC study's main results].

Oxaliplatin in combination with 5-fluorouracil/leucovorin (LV5FU) improves the response rate and survival of patients with metastatic colorectal cancer. The objective of the Mosaic study was to evaluate the efficacy of this association in the adjuvant treatment of stage II and III colon cancer. This international study, including 2,246 patients, compared the efficacy of standard treatment with LV5FU2 alone to that of oxaliplatin-LV5FU (Folfox4 regimen) following R0 resection of the primary tumour. Both treatments were administered every two weeks for six months. At 3-year follow-up, the risk of relapse was decreased by 23% in the Folfox4 group (p = 0.002). The protocol was well tolerated, with an identical overall mortality during treatment (0.5%) in both groups. The main specific complication, peripheral sensory neuropathy was reversible in the great majority of cases. A new analysis at 4-year follow-up (median 48.6 months) confirmed the superior efficacy of the Folfox4 regimen compared to the standard treatment, the reduction in relapse risk being 24% (p = 0.0008). On the strength of these results, oxaliplatin was granted a marketing authorization for the indication adjuvant treatment of stage III colon cancer. Based on the data currently available, physicians should consider adjuvant treatment for stage II patients, making each individual decision for treatment on a case-by-case basis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer--a GERCOR study.

PURPOSE: In metastatic colorectal cancer, a combination of leucovorin (LV) and fluorouracil (FU) with oxaliplatin (FOLFOX) 4 is a standard first-line regimen. The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped in patients who are still responding. This study evaluates a new strategy of intermittent oxaliplatin treatment that is based on FOLFOX7, a simplified leucovorin and fluorouracil regimen with high-dose oxaliplatin. PATIENTS AND METHODS: Previously untreated patients were randomly assigned to either FOLFOX4 administered every 2 weeks until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B). RESULTS: Six hundred twenty patients were enrolled, including an exploratory cohort of 95 elderly or poor prognosis patients. Median progression-free survival and survival times were 9.0 and 19.3 months, respectively, in patients allocated to arm A compared with 8.7 and 21.2 months, respectively, in patients allocated to arm B (P = not significant). Response rates were 58.5% with arm A and 59.2% with arm B. National Cancer Institute Common Toxicity Criteria grade 3 or 4 toxicity was observed in 54.4% of the patients in arm A v 48.7% of patients in arm B. From cycle 7, fewer patients experienced grade 3 or 4 toxicity in arm B. Grade 3 sensory neuropathy was observed in 17.9% of the patients in arm A v 13.3% of patients in arm B (P = .12). In arm B, oxaliplatin was reintroduced in only 40.1% of the patients but achieved responses or stabilizations in 69.4% of these patients. CONCLUSION: Oxaliplatin can be safely stopped after six cycles in a FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin reintroduction.

Adult↗
PubMed2006

Targeted agents for adjuvant therapy of colon cancer.

Adjuvant therapy for colorectal cancer consists primarily of combinations of 5-fluorouracil/leucovorin (5-FU/LV) (with infusional or bolus 5-FU) with oxaliplatin or oral capecitabine. The angiogenesis inhibitor bevacizumab and the epidermal growth factor receptor inhibitor cetuximab have shown activity when combined with 5-FU/LV-based regimens as first-line treatment of advanced disease and are currently being evaluated as part of adjuvant therapy in colon cancer. Bevacizumab is being evaluated in combination with FOLFOX4 (5-FU/LV/oxaliplatin), FOLFOX6, or XELOX (capecitabine/oxaliplatin) in the National Surgical Adjuvant Breast and Bowel Project C08 trial, the AVANT (AVastin adjuvANT) trial, and the Intergroup Rectal Adjuvant trial. Cetuximab is being evaluated in combination with FOLFOX4 and FOLFOX6 in the North Central Cancer Treatment Group (NCCTG) N0147 trial and the Pan European Trials in Adjuvant Colon Cancer (PETTAC) 8 trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Phase II trial alternating FOLFOX-6 and FOLFIRI regimens in second-line therapy of patients with metastatic colorectal cancer (FIREFOX study).

We assessed a schedule alternating 4 FOLFOX and 4 FOLFIRI cycles in 39 patients with 5-FU resistant metastatic colorectal cancer. Patients alternatively received 4 FOLFOX-6 cycles (oxaliplatin 100 mg/m(2), leucovorin 200 mg/m(2) d1 followed by bolus 400 mg/m(2) 5-FU and by a 46-hour 2,400 mg/m(2) 5-FU infusion, every 2 weeks), and 4 FOLFIRI cycles (oxaliplatin replaced by irinotecan 180 mg/m(2) d1) until progression or limiting toxicity. Eigteen patients achieved an objective response (46.1 percent). Median progression-free and overall survivals were 8.8 and 18.7 months, respectively. Only 2 patients (5.1 percent) had Grade 3 oxaliplatin-related sensory-neuropathy. This schedule had so promising efficacy and safety.

Adenocarcinoma↗
PubMed2006

Epirubicin-docetaxel in advanced gastric cancer: two phase II studies as second and first line treatment.

METHODS: We evaluated the Epitax combination (epirubicin 60 mg/m2 and docetaxel 75 mg/m2, every 3 weeks) in advanced gastric cancer (AGC) as second-line treatment after fluorouracil and platinum in 50 patients, then as first-line treatment in 36 patients. We report here the results of these two phase II studies. RESULTS: In the second-line treatment, the response rate (RR) was 15.5%. Grade 3-4 neutropenia was observed in 68% (febrile neutropenia in 40%, one treatment-related death). Median time to progression (TTP) and overall survival (OS) were 2.4 and 5.0 months, respectively. In the first-line treatment, the RR was 19.4%. With prophylactic granulocyte colony-stimulating factor, grade 3-4 neutropenia was reported in 38.9%. Then 22 patients received a second-line and 11 patients a third-line treatment. Median TTP and OS were 4.5 and 12 months, respectively. CONCLUSION: Epitax showed moderate activity in AGC. RR in both trials suggests a non-cross resistance with fluorouracil/platinum combination. The 12-month OS in the first-line treatment could be partly explained by early evaluation and active non-cross resistant second-line therapy.

Adult↗
PubMed2006

[Adjuvant treatment of colorectal cancer].

Colorectal cancer is a real national healthy problem because of high frequency and high rate of mortality. Folfox4 is the new standard treatment since publication of Mosaic' results. Irinotecan associated with 5 fluorouracil (5FU) and leucovorin (LV) failed to demonstrate superiority over LV modulated 5FU. Oral fluoropyrimidines (capecitabine or UFT + LV) are an effective alternative to intravenous 5FU and LV. In stage II colon cancer, treatment strategies are more debated. Some data suggest that chemotherapy is not mandatory for stage II tumors low risk (T3N0 without risk factors). For stage II tumors with high risk factors (T4 or bowel obstruction, perforation, poorly differenciated tumor or, < 10 examined lymphs nodes), Folfox4 and fluoropyrimidine (oral and LV5FU2) should be candidate as adjuvant treatment. Now studies evaluate the role of bevacizumab (Avant, NSABP C08) and cetuximab (Petacc 8 and NCCTG-N0147) in combination with Folfox4 in stage III tumors.

Age Factors↗
PubMed2005

Allergic-type reactions to oxaliplatin: retrospective analysis of 42 patients.

Oxaliplatin is a platinum salt that is particularly effective in treating gastrointestinal tumours. Its increased use has resulted in emergence of allergic reactions, including anaphylactic shock. Allergic reactions to oxaliplatin documented over the last 5 years have been analysed using predefined criteria. The 42 analysed patients had cancer and received a FOLFOX regimen in first line or beyond. Two types of allergy were observed: a type I immediate allergic reaction in 39 patients in whom the most frequent signs were respiratory (50%) and cutaneous (40%); anaphylactic shock that occurred in three patients; type II allergy (immunological thrombopenia) was observed in three patients. All the toxicities were reversible on symptomatic treatment. No predictive factor was evidenced. Anaphylactic shock, is rare but serious, and must be considered in the event of any severe blood pressure decrease. For the non-life-threatening reactions, prolonging infusion duration, "Stop and Go" regimen seem to be effective means of preventing recurrence.

Adult↗
PubMed2005

Intensive systemic chemotherapy combined with surgery for metastatic colorectal cancer: results of a phase II study.

PURPOSE: To evaluate the efficacy and tolerability of the metastatic irinotecan plus oxaliplatin (MIROX) strategy (adjuvant FOLFOX-7 followed by FOLFIRI), in patients with resectable metastatic colorectal cancer. PATIENTS AND METHODS: Forty-seven patients with resectable metastases of colorectal cancer were prospectively enrolled onto this study. Treatment consisted of six cycles of leucovorin 400 mg/m(2), oxaliplatin 130 mg/m(2) in a 120-minute infusion, and fluorouracil (FU) 2,400 mg/m(2) in a 46-hour infusion, every 2 weeks (FOLFOX-7), followed by six cycles of leucovorin 400 mg/m(2), irinotecan 180 mg/m(2) in a 90-minute infusion, bolus FU 400 mg/m(2), and FU 2,400 mg/m(2) as a 46-hour infusion, every 2 weeks (FOLFIRI). Surgery was performed before chemotherapy in 25 patients and after six cycles of FOLFOX-7 in 22 patients (six cycles of FOLFIRI were administered after surgery). RESULTS: All but one of the patients underwent curative surgery. Two patients refused postoperative chemotherapy. Tolerability was generally good. The main toxicities were grade 3 to 4 neutropenia (13%) and thrombocytopenia (11%); no febrile neutropenia or bleeding occurred, and there were no deaths caused by toxicity. Two pathologically confirmed complete responses and 15 partial responses were obtained with FOLFOX-7 in the 22 patients who received this regimen before surgery (overall response rate, 77%; 95% CI, 68 to 86). The median disease-free survival time was 21 months; the median overall survival has not yet been reached. The 2-year overall and disease-free survival rates were 89% and 47%, respectively. CONCLUSION: The MIROX strategy is feasible and well tolerated by patients with resectable metastatic colorectal cancer. Progression-free and overall survival rates are promising, with a median of 38 months of follow-up. This strategy currently is being compared with the leucovorin and FU regimen in a phase III trial.

Adult↗
PubMed2005

First-line therapy for advanced colorectal cancer.

First-line therapy for advanced colorectal cancer is rapidly moving from modulation and infusional administration of fluoropyrimidines in the past decades to more complex and more active regimens, with new chemotherapy drugs, oxaliplatin and irinotecan, and modulated targeted drugs inhibiting angiogenesis or the epidermal growth factor receptor (EGFR). The choice of first-line therapy is becoming more complex and is part of a global strategy also integrating individual prognostic factors, salvage surgery, and second-line therapy. Furthermore, we fear that limited financial resources will also influence the management of this disease.

Antineoplastic Agents↗
PubMed2005

Cetuximab-induced acne.

BACKGROUND: Cetuximab is a member of a new family of antineoplastic agents that inhibit epidermal growth factor receptor (EGFR). These molecules may induce acneiform eruptions. In this study, we aimed at evaluating (a) the characteristics of acne and (b) whether these acneiform eruptions could be improved by classical anti-acne treatments. METHODS: All patients treated with cetuximab in a single institution from October 2003 to May 2004 were prospectively evaluated. The presence of acne, its severity, need for a treatment and response to this treatment were recorded. RESULTS: 13 patients were included: 11 (85%) developed acneiform eruptions after a mean interval of 10 days. It was severe in 4/13 (31%). Comedones were never found and acne involved nonclassical sites in 3/11. Antibiotic treatment was given to 4 and local treatment to 2 patients: it was always efficient. CONCLUSION: Cetuximab-induced acne is frequent, differs from classical acne and may be treated effectively with classical modalities.

Acne Vulgaris↗
PubMed2005

Increased anticancer activity of the thymidylate synthase inhibitor BGC9331 combined with the topoisomerase I inhibitor SN-38 in human colorectal and breast cancer cells: induction of apoptosis and ROCK cleavage through caspase-3-dependent and -independent mechanisms.

The folate analogue BGC9331 is a new thymidylate synthase (TS) inhibitor showing a broad spectrum of cyto-toxic activity against several human solid tumors, including colorectal cancer. In this study, we investigated the anticancer activity of BGC9331 either alone or combined with 5-fluorouracil (5-FU), MTA (multi-target antifolate), oxali-platin and SN-38, the active metabolite of the topoisomerase I inhibitor CPT-11. The antiproliferative activity of each drug and BGC9331-based combinations was investigated in the HT-29 human colorectal cancer cell line and its HT-29/5-FU counterparts selected for resistance to 5-FU. BGC9331 combined with MTA or SN-38 induced synergistic responses in HT-29 cells. Treatment of HT-29 cells with either BGC9331 or SN-38 increased caspase-3 activity and the percentage of apoptotic cells from 3 to 13%. Both drugs also augmented the proteolytic cleavage of the Rho-kinase ROCK-1 that was attenuated by the caspase-3 pathway inhibitor z-DEVD-fmk. BGC9331 combined with SN-38 further increased the percentage of apoptotic cells to 25%, and inhibited cell cycle progression and cell proliferation by 65%. This was accompanied by proteolytic activation of ROCK-1, through both caspase-3-dependent and -independent mechanisms, as shown in caspase-3-deficient MCF-7 breast cancer cells. These encouraging results warrant further preclinical investigations and clinical trials on the use of BGC9331 combined with SN-38/CPT-11 in treatment of patients with advanced colorectal or gastric cancers.

Antineoplastic Agents↗
PubMed2004

Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.

BACKGROUND: The standard adjuvant treatment of colon cancer is fluorouracil plus leucovorin (FL). Oxaliplatin improves the efficacy of this combination in patients with metastatic colorectal cancer. We evaluated the efficacy of treatment with FL plus oxaliplatin in the postoperative adjuvant setting. METHODS: We randomly assigned 2246 patients who had undergone curative resection for stage II or III colon cancer to receive FL alone or with oxaliplatin for six months. The primary end point was disease-free survival. RESULTS: A total of 1123 patients were randomly assigned to each group. After a median follow-up of 37.9 months, 237 patients in the group given FL plus oxaliplatin had had a cancer-related event, as compared with 293 patients in the FL group (21.1 percent vs. 26.1 percent; hazard ratio for recurrence, 0.77; P=0.002). The rate of disease-free survival at three years was 78.2 percent (95 percent confidence interval, 75.6 to 80.7) in the group given FL plus oxaliplatin and 72.9 percent (95 percent confidence interval, 70.2 to 75.7) in the FL group (P=0.002 by the stratified log-rank test). In the group given FL plus oxaliplatin, the incidence of febrile neutropenia was 1.8 percent, the incidence of gastrointestinal adverse effects was low, and the incidence of grade 3 sensory neuropathy was 12.4 percent during treatment, decreasing to 1.1 percent at one year of follow-up. Six patients in each group died during treatment (death rate, 0.5 percent). CONCLUSIONS: Adding oxaliplatin to a regimen of fluorouracil and leucovorin improves the adjuvant treatment of colon cancer.

Adult↗
PubMed2004

[Colon cancer: what is new in 2004?].

Two thousand and three was a particularly dense year for publications and communications on therapy for colon cancer summarizing the real advance performed in this field. The last ten years allowed a rapid evolution for colon chemotherapy with a switch from 5-FU modulated by leucovorin to poly-chemotherapy (fluoropyrimidines with oxaliplatin or irinotecan) integrated into therapeutic strategies, where surgery had a place more and more important in metastatic patients. In correlation with these advances, median survival of patient with metastatic colorectal cancer is between 17 and 22 months. Targeted therapeutics with monoclonal antibody such as EGF inhibitors (cetuximab) or VEGF inhibitors (bevacizumab) had for the first time demonstrated efficacy with encouraging results in randomised trials. In adjuvant situation, LV5FU2 is less toxic than monthly FUFOL and no statistically significant difference could be detected in disease-free or overall survival between the two schedules. Oxaliplatin combined with 5 fluorouracil and leucovorin (FOLFOX4) is the first combination to demonstrate significant superiority over 5 fluorouracil and leucovorin in adjuvant treatment of colorectal cancer. Fluorouracil-based adjuvant chemotherapy benefited to patients with stage II or III colon cancer with microsatellite-stable tumours or tumour exhibiting low-frequency microsatellite instability but may be not those with tumours exhibiting high-frequency microsatellite instability (MSI). These data need to be confirmed by prospective studies before changing our therapeutic references. The number of lymph nodes analyzed for colon cancer staging is itself a prognostic variable on outcome. Laparoscopic surgery of colon cancer is demonstrated as a feasible and safe procedure. Shrinkage of tumours after administration of preoperative chemotherapy and availability of ablative techniques (radiofrequency and cryotherapy) now allow to treat with curative intent metastases initially considered as non-resectable.

Antineoplastic Agents↗
PubMed2004

[Anticancer drugs use evaluation: limits of the approved labeling].

A practice survey was performed in Tenon hospital on 396 consecutive patients treated for solid tumors during 4 weeks in november 2002. 33% of anticancer drugs were off label used. The wording heterogeneity of the different anticancer drugs approved labeling and the lack of anticancer drugs in a number of cancers can explain those results. On one hand, randomised comparative clinical trial, considered as the best level of evidence to obtain a label used, is not always possible in cancerology, especially for rare tumors. One the other hand, pharmaceutical firm are not obliged to asked a label used for an anticancer drugs in spite of high level of evidence. So, label used can not be the own references for anticancer drugs prescribing, therapeutic advanced can be realised and disseminated before their taking into account in the label used.

Antineoplastic Agents↗