PubMed Health⌕ Search

Biomedical subjects

C Louvet

Publications and source records attributed to C Louvet.

At least 73 records · Page 4Linked to original sources
PubMed1997

Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer.

Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m2 as a 2-h infusion on day 1; leucovorin 500 mg/m2 as a 2-h infusion, followed by 5-FU 24-h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m2 for two cycles and increased to 2 g/m2 in case of no toxicity > grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity > or = grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3-4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy.

Adenocarcinoma↗
PubMed1997

Antitumor activity of oxaliplatin in combination with 5-fluorouracil and the thymidylate synthase inhibitor AG337 in human colon, breast and ovarian cancers.

Oxaliplatin, classical [5-fluorouracil (5-FU)] and non-classical (AG337) thymidylate synthase inhibitors have shown promising activity in the treatment of cancer. This study investigates the cytotoxic effects of oxaliplatin in combination with 5-FU and AG337 in cultured human colon (HT29, CaCo2), breast (MCF-7, MDA-MB-231) and ovarian (2008) cancer cell lines, and their derived counterparts selected for their resistance to 5-FU (HT29-5-FU), doxorubicin (MCF-7mdr) or cisplatin (2008C13). Therapeutic experiments were conducted in mice bearing colon-HT29 xenografts and in the GR hormone-independent mammary carcinoma model. In vitro, oxaliplatin shows potent cytotoxic activity in colon (IC50 from 2.1 +/- 1.1 to 5.9 +/- 1.7 microM), ovarian (IC50 = 10 +/- 1.6 microM) and breast cancer cells (IC50 from 7.4 +/- 2.7 to 17.9 +/- 7.1 microM). Oxaliplatin was a potent inhibitor of DNA synthesis and bound to cellular DNA. Surprisingly, the overall amount of oxaliplatin DNA binding was significantly inferior to that induced by isocytotoxic concentrations of cisplatin in HT29 (p=0.026). In vitro, synergistic antiproliferative effects were observed when oxaliplatin was added to 5-FU and AG337. Those synergistic effects of combinations were maintained in colon HT29-5-FU cancer cells. In vivo, 5-FU increased significantly the antitumor activity of oxaliplatin in HT29 xenografts (p=0.0036), and similarly 5-FU and AG337 increased the activity of oxaliplatin in the GR tumor model (p=0.0012). These data may encourage further clinical investigation of oxaliplatin in combination with classical and non-classical thymidylate synthase inhibitors in the treatment of human cancers.

Antimetabolites, Antineoplastic↗
PubMed1997

Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study.

PURPOSE: This multicenter study compared the therapeutic ratio of a monthly schedule of low-dose leucovorin (LV) and fluorouracil (5-FU) bolus with a bimonthly schedule of high-dose LV and 5-FU bolus plus continuous infusion in patients with advanced colorectal cancer. PATIENTS AND METHODS: Of the 448 patients randomly assigned to treatment, 433 were assessable. Treatment A was a monthly regimen of intravenous (IV) LV 20 mg/m2 plus bolus 5-FU 425 mg/m2 for 5 days every 4 weeks. Treatment B was a bimonthly regimen of IV LV 200 mg/m2 as a 2-hour infusion followed by bolus 5-FU 400 mg/m2 and 22-hour infusion 5-FU 600 mg/m2 for 2 consecutive days every 2 weeks. Therapy was continued until disease progression. Second-line chemotherapy, which included 5-FU continuous infusion, was allowed in both arms. RESULTS: The response rates in 348 patients with measurable lesions were 14.4% (monthly regimen) and 32.6% (bimonthly regimen) (P = .0004). The median progression-free survival times were 22 weeks (monthly regimen) and 27.6 weeks (bimonthly regimen) (P = .0012). The median survival times were 56.8 weeks (monthly regimen) and 62 weeks (bimonthly regimen) (P = .067). Grade 3-4 toxicities occurred in 23.9% of patients in the monthly arm compared with 11.1% of those in the bimonthly arm (P = .0004). Patients in arm A more frequently experienced severe granulocytopenia (7.3% v 1.9%), diarrhea (7.3% v 2.9%), and mucositis (7.3% v 1.9%) than patients in arm B. CONCLUSION: The bimonthly regimen was more effective and less toxic than the monthly regimen and definitely increased the therapeutic ratio. However, there was no evidence of increased survival.

Adult↗
PubMed1997

[Early debulking surgery after chemotherapy in advanced cancer of the ovary].

The main prognostic factor in advanced ovarian cancer is the volume of residual disease after the initial laparotomy. Early debulking surgery after several cycles of chemotherapy, before the emergence of resistant cell lines, could improve the prognosis of patients with bulky residual disease. This study concerns patients with advanced ovarian cancer entered into three prospective trials including IV cisplatin and anthracycline-based chemotherapy, early debulking surgery after three cycles of chemotherapy in case of initial residual disease superior 2 cm and intraperitoneal consolidation chemotherapy. Among 160 patients with stage III or IV, 80 (50%) had at least a residual tumor of more than 2 cm in diameter. Early debulking surgery was effectively performed in 54 patients (67.5%), leaving 39 patients with no residue over 2 cm. Twenty-one patients had no macroscopic residual disease. The median survival of all patients with initial residual disease over 2 cm was 23 months. Patients with no macroscopic residual disease at early debulking surgery had a median survival of 44 months. Early debulking surgery appears useful in advanced ovarian cancer with bulky residual disease. The objective of this operation is to achieve no macroscopic residual lesion.

Antineoplastic Agents↗
PubMed1997

[Chemotherapy of advanced colorectal cancers].

The medical treatment of advanced colon and rectum cancer is undergoing a revolution in the light of clinical studies defining the indications for conventional treatments as well as the development of new drugs. In this review, the authors discuss a number of practical questions raised every day by oncological teams. First-line chemotherapy must be administered to patients able to tolerate this treatment by the time of the diagnosis. The standard regiment of 5-FU and folinic acid (FUFOL) is gradually being superseded by more modern regimens, especially based on continuous 5-FU infusion, such as LV5-FU2. New drugs such as oxaliplatin, CPI-11 or tomudex are now available, and their place is currently under evaluation. These new drugs raise the question of the value of second-line chemotherapy, new commonly administered to patients with a persistently good general condition despite escape from first-line treatment. The various possible combinations of new drugs with 5-FU now confirm that current standards will be modified in the near future; while retaining the objective of improving survival, but also quality of life. The progress observed and expected will probably allow the development of more effective adjuvant treatment protocols.

Antimetabolites, Antineoplastic↗
PubMed1996

[Chemotherapy of colorectal cancers with metastases].

The chemotherapy of metastatic colorectal cancer has demonstrated a symptomatic benefit and a prolongation in survival. The modulation of 5-fluorouracil (5-FU) by leucovorin is the current standard treatment. The best protocols include 5-FU 24 or 48 hour continuous infusion on a weekly or bimonthly schedule. The response rate is about 30%, the median progression-free survival is 6 to 8 months and the median survival 10 to 15 months. The toxicity is moderate. New drugs are available or under evaluation: 5-FU prodrugs, raltitrexed, CPT11, oxaliplatin, trimetrexate. Synergisms with 5-FU allow to consider more effective polychemotherapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Antiproliferative effects of the arotinoid Ro 40-8757 in human gastrointestinal and pancreatic cancer cell lines: combinations with 5-fluorouracil and interferon-alpha.

The arotinoid Ro 40-8757 was previously shown to inhibit the growth of a variety of human cancer cell lines derived from breast, lung and uterus. In view of the high incidence of human digestive cancers, and the slow progress in the development of new therapy, we examined in this paper several combinations between the new arotinoid Ro 40-8757, 5-fluorouracil (5FU) and interferon alpha-2a on the growth of nine human cancer cell lines derived from the gastrointestinal and pancreatic system. Half-maximal inhibition of cell proliferation by Ro 40-8757 was observed at concentrations ranging between 0.18 and 0.57 microM, and increased up to 4.7 microM in retinoid-resistant CAPAN 620 pancreatic cells. All-trans-retinoic acid was 70 times less potent. The sensitivity of HT29-5FU-resistant colonic cells was similar to that observed in the parental cells, suggesting an action independent of pyrimidine metabolism. Ro 40-8757 did not induce any differentiation on HT29 cells, as suggested by ultrastructural analysis. The arotinoid did not interact with receptor signal transduction pathways under the control of serum components, such as growth factors as half-maximal inhibiton of growth was similar in HT29-S-B6 cells cultured in the absence or presence of serum. Cell cycle analysis showed that Ro 40-8757 was not acting at a phase-specific transition in HT29 cells and, accordingly, did not induce overexpression of the protein kinase C (PKC)alpha isoform, or conversion of hyperphosphorylated p105 Rb into hypophosphorylated forms. However, the arotinoid induced significant accumulation of the dephosphorylated, active form of the tumour-suppressor protein. Combinations of Ro 40-8757 with 5FU and interferon alpha 2a resulted in an additive but not synergistic antiproliferative action in HT29 cells. Our data support the interest in Ro 40-8757 as a potent anti-cancer drug, especially in combination therapy with 5FU and interferon, in gastrointestinal and pancreatic cancers, where new active therapeutic modalities are urgently needed.

Antineoplastic Agents↗
PubMed1996

Dual modulation of 5-fluorouracil with folinic acid and hydroxyurea in metastatic colorectal cancer.

Leucovorin and 5-fluorouracil (5-FU) can be further modulated with hydroxyurea. Sixty-eight patients with advanced colorectal cancer received every 2 weeks hydroxyurea per os 1.5 g to 2 g days -1, 1, and 2; leucovorin 200 mg/m2 iv over 2 hours started at least 1 hour after hydroxyurea and per os 100 mg/m2 12 hours later, on days 1 and 2; 5-FU, bolus 400 mg/m2 during leucovorin infusion and 24 hours continuous infusion 600 mg/m2, repeated on days 1 and 2. Two complete responses (7%), 8 partial responses (30%), 12 no change (44%), and 5 progressions (19%) were observed among 31 nonpreviously treated patients. Four partial response (11%), 15 no change (43%), and 16 progressions (46%) were observed among 37 pretreated patients. Nineteen were treated after progression on the same regimen without oral leucovorin and hydroxyurea, 1 achieved PR and 10 showed no change. Among them, 6 experienced response or stabilization of longer duration than with previous treatment. Twelve-month survival was 61% in non-pretreated and 43% in pretreated patients as of the start of chemotherapy. Toxicity was mild with nausea in 46%, diarrhea in 37%, and mucositis in 36%. The first-line response rate is in the range of leucovorin and 5-FU alone. Some pretreated patients benefited from this regimen.

Adenocarcinoma↗
PubMed1996

The French experience with infusional 5-fluorouracil in advanced colorectal cancer.

The French contribution to the development of 5-fluorouracil (5-FU) infusion in advanced colorectal cancer includes five randomized trials and specific researches on the 48-hour bimonthly regimen, chronotherapy, and individual dose adaptation. The bimonthly 48-hour LV5-FU bolus and infusion is the standard treatment outside the research protocols and the control arm of the ongoing trials.

Antidotes↗
PubMed1995

[Extravasation of paclitaxel (Taxol)].

Paclitaxel is a new antimitotic derived from yew-tree, used for the treatment of ovarian and breast cancers. The local toxicity of paclitaxel is still poorly known. We report one of the first observations of accidental subcutaneous extravastion of paclitaxel. Local epidermic necrosis was observed and evolution was good with local treatment only. Treatments of such extravasation are discussed.

Aged↗
PubMed1995

[Disseminated intravascular coagulation associated with prostatic cancer].

Disseminated intravascular coagulation (DIC) associated with prostate adenocarcinoma is a bad prognostic sign. Most of the cases are limited to biological abnormalities. Some, however, come to medical attention due to thromboembolic or hemorrhagic complications. We report 4 such cases and review the pertinent literature. The characteristic features are low platelets and coagulation factors in an elderly man. In two out of the four cases, bleeding due to the DIC revealed the cancer. All patients received hormonotherapy and heparin. The worst fate (case 3) was a subacute one with no effect of the drugs and death in a short time. The other cases went into a five- to seven months remission before uncontrollable bleeding led to death. No favorable effect of the chemotherapy was observed. Thus, new treatments are sought for this rare but ominous complication of prostate cancer.

Aged↗
PubMed1995

Cytogenetic study in multiple myeloma at diagnosis: comparison of two techniques.

Cytogenetic studies in multiple myeloma (MM) have been disappointing due to the low mitotic index of plasma cells. Recently the detection of clonal chromosomal abnormalities at diagnosis seemed to be improved by addition of cytokines (IL-6 and GM-CSF) in the culture medium. We performed two parallel total bone marrow cells culture types in 33 stage I, II and III multiple myeloma patients at diagnosis: 3 d without any cytokine, and 4-7 days stimulated with IL-6 and GM-CSF. No clonal chromosomal abnormality was detected in the 12 stage I and II patients either in 3 d or in 4-7 d culture. In stage II patients, abnormalities were observed in 18/21 (85.7%) and in 8/18 (44.4%) in the 3 d culture and the 4-7 d stimulated cultures respectively. Our results suggest that in stage III multiple myeloma at diagnosis, 3 d culture without cytokine may be the better technique to detect clonal chromosomal abnormalities, and, before using cytokines as a reference condition, this 3 d unstimulated culture should be considered.

Aged↗
PubMed1995

[Locoregional recurrences of breast cancer].

AIM OF THE STUDY: To determine the characteristics of 51 cases of isolated local regional breast cancer recurrence. METHODS: Retrospective study from 1980 to 1992, survival calculated according to Kaplan-Meier and log-rank test. RESULTS: Twenty-five patients had had a conservative treatment of her primary tumour, 26 had been treated by modified radical mastectomy. Local regional recurrence rate was 9%: 44% of recurrences after lumpectomy and 43% of recurrences after mastectomy occurred within 2 years after the initial treatment. Site of local regional recurrence was chest wall only (16 cases), breast only (15 cases) or axillary or supraclavicular node with or without chest wall or breast involvement (20 cases). The actuarial 5-year survival rate after recurrence is 54%. It depends on the time to recurrence (40% if time to recurrence was less than 2 years, 68% if more than 2 years, p < 0.10), on initial node involvement (36% for N+, 71% for N-, p < 0.15) and on the site of recurrence (chest wall: 43%; breast: 48%; regional node: 12%, p < 0.10). CONCLUSION: Like in the literature, severe recurrences are early recurrences, lymph node recurrences and recurrences following a primary tumour with involved axillary nodes.

Actuarial Analysis↗
PubMed1994

The arotinoid Ro 40-8757 has antiproliferative effects in drug-resistant human colon and breast cancer cell lines in vitro.

We have examined the antiproliferative effects of the arotinoid Ro 40-8757 in 3 drug-resistant human adenocarcinoma cell lines: the colonic cells HT29-5FU and CaCo2, and the mammary cells MCF-7mdr1. Whereas all-trans retinoic acid had no effect at the concentration of 10(-6) M, Ro 40-8757 was found to exert a high antiproliferative action with similar inhibitory potency (IC50) in drug-resistant and parental cell lines (range, 0.06 x 10(-6) to 0.57 x 10(-6) M). We conclude that: (1) thymidylate synthase is not involved in the mechanism of action of Ro 40-8757; (2) the mdr1 gene product does not recognize this retinoic derivative, and (3) Ro 40-8757, alone or in combinations with other cytotoxic drugs, can be very useful in patients with progressive disease after conventional chemotherapy.

Adenocarcinoma↗
PubMed1994

[Detection of ovarian adenocarcinoma in the occasion of cerebrovascular complication associated with consumption coagulopathy].

A 58 year-old woman was hospitalized for an hemorrhagic stroke, associated with a consumption's coagulopathy, related to a stage Ic ovarian carcinoma. After surgery and chemotherapy, hemostasic disorders disappeared. The same disorders occurred at tumoral relapse. Relationships between thrombotic or haemorrhagic manifestations and neoplasms are discussed, with emphasis on singularity of such phenomenon in ovarian carcinoma.

Adenocarcinoma↗
PubMed1993

Folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide in metastatic breast cancer.

60 patients with metastatic breast cancer were entered in a phase II study using folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide. 47 had measurable visceral metastases and 13 had exclusively bone metastases. 36 had received previous adjuvant or metastatic treatment (33/36 with anthracycline-based regimens). Overall response rate in visceral metastatic patients was 57.1% [95% confidence interval (CI) 35.4-78.8%]; 45.5% and 70% in previously and non-previously treated patients, respectively; duration of response was 9 and 13 months, respectively. 10 out 13 patients with exclusive bone metastases improved for a median time of 18 months. Median survival was 22 months for the 60 patients; 18 and 31 months for previously and non-previously treated patients, respectively. Cyclophosphamide was scheduled only in the absence of nadir grade 4 neutropenia. However, this toxicity occurred in the first 7 patients. For this reason, we chose to avoid cyclophosphamide in patients over 60 years, or with a performance status of 1-2, or who had received previous chemotherapy. Overall, cyclophosphamide was stopped due to nadir grade 4 neutropenia in 17/24 patients for whom this drug was planned. When mitoxantrone, 5-fluorouracil and folinic acid were used at the doses scheduled, the addition of cyclophosphamide appeared feasible in only about 25% of the patients. Furthermore, survival was identical for patients receiving or not receiving cyclophosphamide. Therefore, cyclophosphamide does not contribute substantially to this regimen. This study confirms the value of folinic acid, 5-fluorouracil and mitoxantrone in metastatic breast cancer.

Adult↗