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F Morvan

Publications and source records attributed to F Morvan.

At least 19 recordsLinked to original sources
PubMed1999

[Intensive chemotherapy and autograft of hematopoietic stem cells in the treatment of metastatic cancer: results of the national protocol Pegase 04].

UNLABELLED: We report hereby the results of the french multicentric randomized PEGASE 04 protocol established to evaluate the impact on survival of high-dose chemotherapy over conventional chemotherapy for MBC patients. PATIENTS AND METHODS: Inclusion criteria were: age < or = 60 year, PS < 2, adenocarcinoma initially metastatic or in first relapse, chemosensitive disease. Randomization was done after 4-6 courses of conventionnal chemotherapy between high-dose (Mitoxantrone, 45 mg/m2, Cyclophosphamide: 120 mg/kg, Melphalan: 140 mg/m2), and the pursuit of the same conventionnal chemotherapy. Between 09/92 and 12/96, 61 chemosensitive patients were enrolled: 29 were referred to standard chemotherapy, 32 to intensive therapy. At randomization, 13 pts (21.3%) were in complete response and 48 in partial response. RESULTS: The median progression-free survivals were 20 and 35.3 months in the standard and intensive groups (p=0.06). The relapse rates were respectively 79.3% vs 50.8% at 3 years and 90.8% vs 90.7% at 5 years. The median overall survivals were 20 and 43.4 months, with an overall survival rate of 18.5% vs 29.8% at 5 years (p=0.12). CONCLUSION: The CMA regimen could prolong the progression-free survival of MBC patients, however without any significant impact on overall survival.

Adult↗
PubMed1999

High-dose epirubicin and cyclophosphamide every two weeks as first-line chemotherapy for relapsing metastatic breast cancer patients.

BACKGROUND: Metastatic breast cancer remains incurable with conventional chemotherapy. For any specific chemotherapy, higher dose intensity may be achieved with either increased doses per cycle, or shortened intervals between courses, or both. We demonstrate here the feasibility and encouraging results of a high-dose combination regimen administered every two weeks. PATIENTS AND METHODS: Women with metastatic breast cancer were treated every 14 days for 6 courses with 75 mg/m2 epirubicin and 1200 mg/m2 cyclophosphamide, followed by conventionally-delivered (q 3-4 weeks) chemotherapy. The treatment was to be resumed regardless of the neutrophil count, except in instances of febrile neutropenia. Prophylactic oral antibiotherapy was given, while hematopoietic growth factors and stem cell support were not employed. RESULTS: Eighty-six patients were treated between May 1986 and June 1995. Their median age was 43 years (26-69). Grade 3-4 neutrophil toxicity was observed after 86% of the courses, resulting in febrile neutropenia in 5%-18% of the patients, and the rehospitalization of 5%-10%. The median given/planned dose intensity was 97% (79-106). The objective response rate in 84 evaluable patients was 54% (95% confidence interval (95% CI): 43-65), with a complete response rate of 11%, and a 14% rate of outright progression. Median progression-free survival was 16 months and median overall survival 32 months. Multivariate analysis retained previous adjuvant chemotherapy as a negative survival prognostic factor. CONCLUSIONS: This dose-intensive anthracycline-based regimen is feasible with manageable morbidity despite pronounced myelotoxicity, and yields encouraging survival rates.

Adult↗
PubMed1998

The pro-oligonucleotide approach: solid phase synthesis and preliminary evaluation of model pro-dodecathymidylates.

A modified phosphoramidite method has been designed for the solid-phase synthesis of two dodecathymidine phosphotriesters and two dodecathymidine thionophosphotriesters. In these analogs, each internucleoside link bears an S -acyl-2-thioethyl (Me-SATE or tBu-SATE) group removable upon esterase activation. Efficient synthesis of these lipophilic analogs was achieved thanks to the use of a photolabile linker anchored to the solid support in combination with thymidine-3'- O -phosphoramidites having a SATE group in place of the regular 2-cyanoethyl one. Both dodecathymidine phosphotriester and thionophosphotriester having S -acetyl-2-thioethyl groups were found to be stable in the presence of snake venom and calf spleen phosphodiesterases whereas, upon incubation in CEM cell extracts, they were selectively hydrolyzed to the anionic parent dodecathymidylate and dodecathymidine phosphorothioate, respectively. In addition, Me-SATE-protected dodecathymidine thionophosphotriester was stable in mouse and human sera as well as in human gastric juice. These results depict the potential of SATE-protected oligonucleotides as prodrugs of antisense oligonucleotides.

Animals↗
PubMed1997

5-Fluorouracil (5-FU) continuous intravenous infusion compared with bolus administration. Final results of a randomised trial in metastatic colorectal cancer.

The aim of this Phase III, balanced randomised trial was to compare continuous intravenous infusion (CVI) of 5-FU with bolus (B) administration for metastatic colorectal cancer (CRC). One hundred and fifty-five non-pretreated patients were randomised to receive CVI 5-FU at a dose of 750 mg/m2/day (d), 7 d every 21 d (n = 77), or bolus 5-FU 500 mg/m2/d x 5 d every 28 d (n = 78). Incremental dose escalation at 50 mg per step was recommended in the absence of toxicity. All the patients had measurable metastatic disease (M), particularly, liver and a good performance status (WHO grade 0-1). Dose intensity was significantly higher in CVI than in the bolus group: 1369 mg/m2/week versus 558 mg/m2/week (P = 0.0001). Grade II-IV stomatitis was more frequent in the CVI group (31% versus 9%; P < 0.0001) as was hand and foot syndrome (14% versus 3%; P < 0.001). Diarrhoea (22% versus 12%) and grade III granulocytopenia (2% versus 6%) were comparable. Responses were more frequent in the CVI (26%) than in the bolus group (13%) (P < 0.04); progression-free survival was higher for the CVI group (P = 0.04), but there was no statistical difference in overall survival (median: 10 months (m) compared to 9 m), and 1 year survival (SD) 42% (6%) versus 40% (6%). In the multivariate analysis, survival was better for patients with a good PS, well-differentiated adenocarcinomas and a primary tumour without serosal extension. In conclusion, with a higher dose intensity, CVI 5-FU improved tumour control, but not overall survival.

Antimetabolites, Antineoplastic↗
PubMed1997

Comparative stability of eight different triple helices formed by differently modified DNA or RNA pyrimidine strands and a DNA hairpin.

The comparative stability of eight different triplexes constituted with 16-mer pyrimidine-modified oligodeoxynucleotides (wild-type ODN, PS-ODN, alpha-ODN, or alpha-PS-ODN) or oligoribonucleotides (wild-type ORN, alpha-ORN, 4'-thio-ORN, or 2'-O-MeORN) and a DNA hairpin, termed H36, was studied in five different buffers by UV melting curve analysis. The composition of buffers varied in pH (5.5 and 6.5), in salt concentration (100 mM and 1 M Na+), and in the presence or absence of divalent cation (0 or 3 mM Mg2+) or spermine (0 or 1 mM). At pH 5.5, the eight triplexes are formed with Tm values ranging from 24.7 degrees C to 50.9 degrees C (delta G298K between -8.1 and -16.8 kcal/mol). At pH 6.5, the triplexes are less stable, and thus 4'-thio-ORN and PS-ODN showed broad transitions that did not allow us to conclude triplex formation. An increase of salt concentration or the presence of spermine stabilizes the triplexes, whereas Mg2+ has a destabilizing effect (excepted for alpha-ORN). In general ORN:H36 and 2'-O-MeORN:H36 triplexes were the most stable. Finally, introduction of alpha-anomeric nucleosides led to an alpha-ORN analog that showed low binding with H36 and to alpha-ODN and alpha-PS-ODN analogs. Triplexes formed with alpha-ODN were slightly less stable than those formed with unmodified ODN. Surprisingly, introduction of phosphorothioate in an alpha analog led only to a low destabilization.

Base Sequence↗
PubMed1997

Concomitant chemoradiotherapy followed, where feasible, by surgery for cancer of the esophagus.

PURPOSE: To conduct a multicenter phase II study of a concomitant combination of chemotherapy and radiotherapy followed by surgery, where feasible, in patients with nonmetastatic esophageal tumor, stratified on operability at diagnosis. METHODS: Each cycle consisted of fluorouracil (5FU) 800 mg/m2/d by continuous intravenous (IV) infusion on days 1 to 5, cisplatin (CDDP) 50 mg/m2/d IV bolus on days 1 and 8, hydroxyurea (HU) 1.5 or 2 g/d orally on days 8 to 12 and concomitant radiotherapy 20 Gy in 10 fractions over 12 days. All patients were to receive two cycles on days 1 and 22. If feasible, surgery was performed 3 to 6 weeks after cycle two completion. Otherwise, a third cycle was administered. RESULTS: Eighty-eight patients were included between September 1990 and September 1993. Of the 47 operable patients, 41 (87%) underwent surgery and 38 (81%) had a complete resection. No residual primary tumor was found in the surgical specimen in 17 cases (36%), and only microscopic foci in 13 (28%). Two-year overall and disease-free survival probabilities were 51% (95% confidence interval [CI]; 37 to 65) and 43% (95% CI, 28 to 57), respectively. Among the 41 inoperable patients, 12 (29%) became operable. Seven (17%) had complete resection, two incomplete resection, and three exploratory surgery. Two-year overall and disease-free survival probabilities were 29% (95% CI, 15 to 43) and 27% (95% CI, 13 to 40), respectively. Five deaths occurred during chemoradiotherapy, six postoperatively and four in patients with evidence of cancer. Five late complications (one myelopathy) were observed. CONCLUSION: Despite a high histologic response rate in initially operable patients, overall survival was similar to that observed in other preoperative chemoradiation series because of substantial toxicity.

Aged↗
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↗
PubMed1996

Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group.

PURPOSE: To determine whether a combination chemotherapy regimen that contains epirubicin (fluorouracil, epirubicin, and cyclophosphamide [FEC]) is superior to the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in premenopausal women with axillary node-positive operable breast cancer. PATIENTS AND METHODS: The International Collaborative Cancer Group (ICCG) conducted a large randomized trial in which two alternative schedules were used according to participating center: CMF1 versus FEC1 and CMF2 versus FEC2. RESULTS: Seven hundred fifty-nine patients were entered onto the trial. At a median follow-up time of 4.5 years, no significant benefit for the anthracycline-containing regimen was observed in terms of relapse-free (P = .61) or overall survival (P = .13). FEC1 and CMF1 appear to be of similar efficacy, but there is a suggestion that FEC2 may be superior to CMF2, since patients who received FEC2 had improved overall (P = .02) and relapse-free survival (P = .03) rates. Nausea and vomiting and alopecia were more common in the epirubicin-containing regimen (P = .001). CONCLUSION: We conclude that the FEC2 regimen, in which epirubicin replaced the methotrexate in CMF, is the preferable adjuvant chemotherapy regimen for premenopausal patients with operable axillary node-positive breast cancer.

Adult↗
PubMed1996

Efficacy and tolerance of vinorelbine and fluorouracil combination as first-line chemotherapy of advanced breast cancer: results of a phase II study using a sequential group method.

PURPOSE: To assess the antitumor efficacy and safety profile of the combination of Fluorouracil (5FU) and vinorelbine given as first-line therapy to patients with advanced breast cancer. PATIENTS AND METHODS: As defined in the seven consecutive steps of a phase II group sequential design, 63 patients received 5FU 750 mg/m2/d for 5 consecutive days as a continuous infusion and vinorelbine 30 mg/ m2 on days 1 and 5 as a short intravenous (I/V) infusion every 3 weeks. RESULTS: Forty-one of 63 patients achieved an objective response, which allowed us to discontinue the study and reject a response rate less than 50% with a statistical power of 90%. The unbiased estimate of the response rate was 61.6%. Response rate did not differ significantly according to the following: (1) type of prior adjuvant therapy (none, n = 23; without anthracycline, n = 6; with anthracyline, n = 34); (2) site of metastatic disease; and (3) number of metastatic sites. The median time to progression was 8.4 months. The median response duration was 12.3 months, and the median duration of complete response (CR), from the first assessment of CR, was 7.3 months. The median overall survival time was 23 months (28.1 months for patients with a CR). The main toxicities (grades 3 and 4) were neutropenia (90% of patients), infection (12.7%), mucositis (37%), and constipation (9.5%). Nevertheless, treatment could be given on an outpatient basis to the majority of patients, and the median relative dose-intensity was 86%. CONCLUSION: This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.

Adult↗
PubMed1996

[Pregnancy after breast cancer].

In what ways can a premenopausal woman be pregnant after a breast carcinoma's treatment? A survey organized in 1985 by the French Gynecologic Association gave us the opinion of 316 gynecologists: 50% of them disagreed with this pregnancy because of an accrued risk of relapse. 68 observations were collected including 41 of full term pregnancies; the survival curves were, in each group, similar to those of the controls at the same stage. The interruption doesn't improve the prognosis. This confirms the whole of the published series: a subsequent pregnancy doesn't seem to affect the prognosis of a breast carcinoma; it is important to take the contraception into account so that this pregnancy shall be really desired.

Adult↗
PubMed1995

4'-Thio-RNA: synthesis of mixed base 4'-thio-oligoribonucleotides, nuclease resistance, and base pairing properties with complementary single and double strand.

4'-Thio-beta-D-oligoribonucleotides (12 mer and 16 mer) containing a mixed base sequence were synthesized via the phosphoramidite solid support approach. These RNA analogs showed very good nuclease resistance as compared with wild-type RNA. Furthermore, 4'-thio-beta-D-oligoribonucleotides were shown to hybridize with a complementary DNA or RNA strand to form a duplex or with a DNA hairpin to form a triple helix. 4'-Thio-RNA binds more tightly to its complementary RNA strand than to its complementary DNA strand. A 4'-thio-RNA:RNA duplex is as stable as a 2'-O-methyl-RNA:RNA duplex. 4'-Thio-RNA, however, forms a 4'-thio-RNA:DNA:DNA triplex with a stability similar to the corresponding triplex with all wild-type DNA.

Amides↗
PubMed1995

[Classification of cancers for clinical use].

The clinical classification of cancers has become necessary along the past decades to optimize treatments according pronostic and to allow scientific exchanges among the medical oncology community. The TNM staging system, with the derivates classifications, and the use of pronostic models, is now universal and applied to almost all human neoplasms. Therefore, the classification of cancers is now become an evoluting instrument of long-term evaluation of neoplastic diseases as well as medical oncology practice.

Humans↗
PubMed1995

Phase II randomized study of paclitaxel versus mitomycin in advanced breast cancer.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has been shown to be an effective agent in the treatment of metastatic breast carcinoma. This multicenter randomized study compared paclitaxel 175 mg/m2 given as a 3-hour infusion every 3 weeks with mitomycin 12 mg/m2 given as an intravenous infusion every 6 weeks. Eighty-one patients have been randomized, and preliminary results of a planned analysis of the first 36 evaluable patients per arm are reported. Pretreatment characteristics were well balanced between the two groups. All patients previously have received chemotherapy for metastatic disease, and half had both adjuvant therapy and chemotherapy for metastatic disease. All but one patient previously had received anthracyclines. Of the first 81 randomized patients, 72 were evaluable for response and toxicity (four never treated, five concomitant hormonotherapy). Partial responses were seen in 17% of patients in the paclitaxel arm and 6% in the mitomycin arm (P = .14). Crossover to paclitaxel therapy following progression on mitomycin achieved an objective response rate of 24% (five of 21 patients). Responses to paclitaxel therapy lasted for a median duration of 9.1 months (range, 6.2 to 12+ months). Median time to progression was significantly longer in the paclitaxel arm (3.5 months v 1.6 months; P = .026). The quality-of-life-adjusted analysis confirmed the advantage of paclitaxel therapy, even when the delay of disease progression was adjusted for important adverse events. Adverse events, most importantly neutropenia and neuropathy, were more frequently observed in the paclitaxel arm. However, patients remained on paclitaxel therapy for many more courses than did those treated in the mitomycin arm. In conclusion, paclitaxel 175 mg/m2 given as a 3-hour intravenous infusion has been demonstrated to be an active agent in the treatment of chemotherapy-refractory advanced breast cancer, even after therapy with mitomycin has failed.

Adult↗
PubMed1995

[Inflammatory cancer of the breast: review and experience at Saint-Louis hospital].

Inflammatory breast cancer represents about 1 to 6% of all breast cancers. It has a sudden onset and affects women of the same age as other breast cancers. Its particular feature is the almost constant development of metastases. The 5-year survival after surgery or surgery and radiotherapy varies between 0 and 28% with a median survival of 18 months. The use of anthracycline-based chemotherapy has doubled the median survival, but has not achieved cure. Clinical research is directed towards therapeutic intensification with or without autologous bone marrow transplantation. The authors report their experience at Hôpital Saint-Louis.

Adolescent↗
PubMed1994

Sequence-specific interaction of alpha-beta-anomeric double-stranded DNA with the p50 subunit of NF kappa B: application to the decoy approach.

The potential use of alpha-beta-anomeric duplex oligonucleotides to inhibit transcription factor activity by the decoy approach is investigated in this report. Indeed, several alpha-beta-anomeric heteroduplexes display a sequence-specific interaction with the p50 subunit of the transcription factor NF kappa B. Used in a decoy approach, these duplexes interact strongly enough with this transcription factor to modulate the expression of a reporter gene, under the control of NF kappa B. However, all the alpha-beta-anomeric heteroduplexes do not interact with the p50 subunit; the sequence of the chirally natural beta-anomeric strand may explain the different recognition properties of the protein. The analysis of the appropriate beta-anomeric sequences is consistent with a preferential interaction of the p50 subunit with one strand of double-stranded DNA.

Base Sequence↗
PubMed1993

Rapid determination of the affinity of 28- and 14-mer phosphorothioate oligonucleotides for HIV-1 reverse transcriptase by fluorescence spectroscopy.

Intrinsic fluorescence of human immunodeficiency virus type 1 reverse transcriptase (E.C. 2.7.7.49) and displacement experiments of a fluorescent template.primer probe were used to study the interaction of the enzyme with several types of 28- and 14-mer normal or phosphorothioate oligodeoxycytidinylates and their duplexes with poly(rI). The two methods gave convergent results and allowed in each case fast determinations of ligand affinities for the enzyme. The dissociation constants (Kd) obtained from intrinsic fluorescence changes were slightly lower than those determined from the less direct competitive displacement experiments. In all cases, the enzyme displayed better recognition of the hybrid than of the unannealed oligonucleotide. The Kd values of phosphorothioate oligomers and their hybrids were lower than those of the corresponding normal oligomers and hybrids, but the difference was not as significant as in the case of the Ki constants for (dC)28 and S(dC)28 (Majumdar et al. (1989) Biochemistry 28, 1340). The affinities of the annealed phosphorothioate oligodeoxycytidinylates for the enzyme were found to be larger than for any other compounds in this series (Kd of poly(rI).S(dC)28: 0.28 nM at 25 degrees C). Changing the beta stereochemistry of the oligomer bases to alpha did not alter the affinity of the oligodeoxycytidinylate and its hybrids for the enzyme.

Base Sequence↗
PubMed1993

Triple helix formation by alpha-oligodeoxynucleotides: a vibrational spectroscopy and molecular modeling study.

The structures of triple helices alpha dT6.beta dAn.beta dTn, alpha dT12.beta dAn.beta dTn, alpha dC12+.beta dGn.beta dCn, and alpha dC12+.beta rGn.beta rCn have been studied by Fourier transform infrared spectroscopy, Raman spectroscopy, and molecular mechanics calculations. The sugar conformations in these triplexes have been determined by vibrational spectroscopy. Our results show the existence of only S-type sugars in the alpha dT12.beta dAn.beta dTn triple helix. Both S- and N-type sugar infrared and Raman markers have been detected in the spectra of alpha dC12+.beta dGn.beta dCn. Molecular mechanics refinements taking into account vibrational spectroscopy data constraints allow us to propose third strand hydrogen-bonding schemes and third strand polarities in triple helix models. For alpha dT12.beta dA12.beta dT12 the third strand forms reverse Hoogsteen hydrogen bonds with the beta dA12 strand and therefore is parallel to the purine strand. In contrast, for alpha dC12+.beta dG12.beta dC12 calculations show that only a model in which the third strand is Hoogsteen base paired and antiparallel to the purine strand of the Watson-Crick duplex is compatible with spectroscopic data.

Hydrogen Bonding↗