Biomedical subjects

P Pouillart

Publications and source records attributed to P Pouillart.

At least 19 recordsLinked to original sources

PubMed1999

Regioselective synthesis and biological profiling of butyric and phenylalkylcarboxylic esters derivated from D-mannose and xylitol: influence of alkyl chain length on acute toxicity.

Regiospecific synthesis of 12 novel n-butyric and phenylalkylcarboxylic monoesters of mannose and xylitol was achieved. The strategy adopted, avoided a tedious intramolecular transesterification step, previously described for the synthesis of analogous compounds and permitted the facile synthesis of a new generation of stable derivatives. The general tolerance of the drugs has been assayed after intravenous administration of a bolus dose into mice. Monobutyric esters showed a low toxicity commensurate with the requirements for future development. A relationship was observed between chain length and toxicity. In contrast, phenylacetic, 3-phenylpropionic and 4-phenylbutyric esters were found to be toxic. Phenylbutyric esters induced marked and specific neuromuscular damage. Preliminary biological investigations of the new series of monobutyric esters showed them to retain the benificial biological properties of butyric acid whilst remaining relatively non toxic. They induced an inhibition of in vitro proliferation of 10 human cases of de novo acute myeloid leukemia (AML) primary cultures and AML established cell lines. AML blasts growth appeared to be blocked and cell differentiation was established. Transcription and expression of maturation markers and finally apoptosis were observed. Moreover, human gamma-chain hemoglobin (HbF) synthesis in erythroleukemia cells was stimulated by monobutyric esters. Mannose and xylitol butyric derivatives would appear to have exciting potential in treatment of beta-Hemoglobinopathies, sickle cell anemia and cancer.

Animals↗

PubMed1998

No significant predictive value of c-erbB-2 or p53 expression regarding sensitivity to primary chemotherapy or radiotherapy in breast cancer.

To document whether c-erbB-2 over-expression or p53 accumulation in tumour cells was predictive of response to chemo- or radiotherapy, we analyzed a population of patients with breast cancer assigned to neo-adjuvant therapy (median follow-up: 54 months). T2/T3-N0N1b-M0 tumours (329 cases) were treated either by FAC chemotherapy or by radiotherapy before surgery, and the clinical response was classified as complete or incomplete. Expression of c-erbB-2 and p53 was retrospectively evaluated by immunohistochemistry. Proliferation rate was assessed by means of MIB-1 antibody and by S-phase fraction. A complete response to chemotherapy was observed in 38/167 patients (23%). Complete response rate was 20% in c-erbB-2-negative tumours, and rose to 31% in tumours with c-erbB-2 over-expression, but this trend was not statistically significant. There was no correlation between p53 staining and response to treatment, whereas chemosensitivity was found correlated with histological grade and S-phase. A complete response to radiotherapy was observed in 64 of the 156 evaluable patients (41%). Complete response rate was 41% in c-erbB-2- or p53-negative tumours, 54% in tumours with c-erb-B-2 over-expression, and 44% in tumours with p53 accumulation. There was no correlation between response to radiotherapy and histological grade or proliferative rate. No prognostic value was found for c-erbB-2 or p53 expression, whereas the 5-year survival rate was 85% for patients presenting a tumour with a low proliferating index (MIB-1 < 10%), and 68% for patients presenting a tumour with a high proliferative index. In multivariate analysis, node status (RR = 2), MIB-1 immunostaining (RR = 2), and tumour size (RR = 1.8) were found to be associated with survival. These results indicate that c-erbB-2 or p53 expression is not significantly associated with tumour response to neo-adjuvant chemo/radiotherapy in our series of breast cancers.

Breast Neoplasms↗

PubMed1998

[Chemotherapy and hormonotherapy of breast cancers].

The interest of adjuvant chemotherapy and hormonotherapy is now established in breast cancer. Their indications are more and more precise, even though progresses are still warranted to better take into account the prognostic factors in treatment strategies. Metastatic breast cancer is essentially incurable. However, a standard therapy given according to the clinical and biological presentation is able to insure acceptable response rate, overall survival and quality of life. For these reasons, innovative strategies may be evaluated under good medical practice conditions and considered as an ethical obligation.

Antineoplastic Agents, Hormonal↗

PubMed1998

Is primary chemotherapy useful for all patients with primary invasive breast cancer?

Chemotherapy dose intensification in breast tumours is being evaluated in many multicentre trials, its indication being based on a clinical response in high-risk patients, thus selecting for tumours with rapid proliferation and low resistance. However, results from randomized trials are still pending. Clinical and pathological responses to therapy are valuable surrogate endpoints following primary chemotherapy. They will make it possible to distinguish at an early stage between patients who still retain an apoptotic response to chemotherapy and those patients whose disease will progress rapidly due to resistance mechanisms. For practical purposes, patients at risk and capable of responding represent the population of choice for primary systemic chemotherapy. Thus, by investigating mechanisms of response and resistance during the first courses of treatment we may target chemotherapy at those patients likely to benefit most from this treatment. A number of immunotherapy and vaccination trials are being conducted in many different centres. There is a lot of anecdotal evidence that cancer vaccines could help patients, but little yet in the way of solid, reproducible clinical data. Best responses to clinical testing would ideally be expected in early-stage disease because there is less tumour bulk and the patient's immune system is still able to respond. Patients with early breast cancer who are at high risk of recurrence and who have failed to respond to primary chemotherapy might be given the option of participating in adjuvant vaccination trials following the completion of local therapy.

Antineoplastic Agents↗

PubMed1998

Malignant giant-cell tumours of bone. Clinico-pathological types and prognosis: a review of 29 cases.

Twenty-nine patients with malignant giant-cell tumours of bone (GCT) were followed-up for between 6 months and 18 years. Seventeen of the tumours were primary and 12 were due to malignant degeneration of initially benign lesions. The clinical features did not differ from those of benign GCT, except for a higher incidence in the distal tibia and sacrum. Anaplastic GCTs were included in the study because their clinical and radiographic features and prognosis were no different from those of the GCT grade III of Jaffe. Eighteen of the tumours were grade III, and 11 were anaplastic. This retrospective study was intended to assess the effects of chemotherapy and surgery for malignant GCT. Three treatment groups were selected, in which treatment was either by surgery alone, surgery plus chemotherapy, or radiotherapy alone.--The prognosis was poor and the 5 year tumour-free survival rate in the series was 50%. The prognosis was the same for primary as for secondarily malignant tumours. There was no statistical difference in survival between malignant grade III and anaplastic malignant tumours. The one-year survival rate for patients treated by chemotherapy and surgery was statistically higher (chi2 test) than for persons treated by surgery alone. However, the five-year survival rate and the actuarial survival curves were not statistically different in the two groups (log rank test).--Chemotherapy appears to be of some value in the treatment of these malignant tumours but a larger series is required to confirm the efficacy of this approach.

Adult↗

PubMed1998

Treatment of liver metastases from uveal melanoma by combined surgery-chemotherapy.

AIMS: To investigate sporadic results demonstrating prolonged survival after surgical resection and/or intraarterial chemotherapy (IACH) for liver metastases from uveal melanoma. METHODS: From December 1992 to March 1997 every patient with liver metastases from uveal melanoma was enrolled in a prospective study including: (1) aggressive surgical approach removing as much liver disease as possible; (2) implantation of an intraaterial catheter; (3) intraarterial chemotherapy for 6 months. 75 patients were enrolled: 38 men, 37 women, mean age 51 years (range: 18-72), mean time from initial diagnosis of uveal melanoma to liver metastases 37 months (ranged: 1-168). RESULTS: Disseminated disease in both lobes was present in all but one patient. Macroscopically curative surgery was possible in 27.5%. Significant tumour reduction was performed in 49.3% and a simple biopsy was possible in 23.2%. Eight patients did not receive chemotherapy and died soon after. IACH included Fotemustine and/or DTIC-Platinum for 4-9 cycles. Overall median survival was 9 months; very similar to non-operated historical controls. In the 61 patients receiving complete treatment surgery plus chemotherapy, median survival improved to 10 months. When curative resection was possible, survival increased to 22 months (P < 0.001). CONCLUSIONS: Aggressive surgical resection, when possible, appears to be the best method of improving survival of liver metastases from uveal melanoma. New drug combinations are also required to improve survival.

Adult↗

PubMed1998

Randomized trial comparing protracted infusion of 5-fluorouracil with weekly doxorubicin and cyclophosphamide with a monthly bolus FAC regimen in metastatic breast carcinoma (SPM90).

Infusional 5-fluorouracil in advanced breast cancer has been associated with improved clinical response rates when compared with conventional bolus therapy. As a first line of chemotherapy in proven metastatic breast carcinoma, 258 women were randomly assigned to receive FAC consisting of 5-fluorouracil (F) 600 mg m(-2) intravenously (i.v.) over 1 h on days 1, 2 and 3, doxorubicin (A) 50 mg m(-2) i.v. bolus on day 1 and cyclophosphamide (C), 400 mg m(-2) i.v. bolus on days 1, 2 and 3 or 'FULON' consisting of 5-fluorouracil 250 mg m(-2) day(-1) continuously infused from day 1 to day 22, doxorubicin 15 mg m(-2) i.v. bolus on days 1, 8, 15 and 22 and cyclophosphamide 300 mg m(-2) i.v. bolus on days 1, 8, 15 and 22. Chemotherapy courses were administered 4-weekly for the bolus regimen and 6-weekly for FULON. Pretreatment characteristics were identical between the two groups. Response rates were 54% in the FAC arm and 53% in the FULON arm. Time to progression was 14 months in the FAC arm and 12 months in the FULON arm. Differences were not statistically significant. Median overall survival duration for all patients was 22 months. Haematological toxicity was more severe in the bolus-treated group (P = 0.05), as were nausea and vomiting (P < or = 0.01). We conclude that the two regimens appeared equally effective but have different toxicities.

Adult↗

PubMed1998

Butyrate-stable monosaccharide derivatives induce maturation and apoptosis in human acute myeloid leukaemia cells.

The rapid degradation and subsequent lack of efficacy of n-butyric acid in vivo has been improved by the synthesis of monosaccharide stable pro-drugs of butyric acid. We studied the effects of D1 (O-n-butanoyl-2,3-O-isopropylidene-alpha-D-mannofuranoside), G1 (1-O-n-butanoyl-D,L-xylitol), and F1 (1-O-n-butanoyl 2,3-O-isopropylidene-D,L-xylitol) on the maturation and proliferation of AML cell lines HL 60 and FLG 29.1 and of purified blast cells from 10 cases of de novo acute myeloid leukaemia (AML). AML cell maturation was measured by surface antigen expression, morphology and cytochemistry. Toxicology in mice was also evaluated (DL50 1000 mg/kg). In HL 60 cells G1 and D1 increased the expression of CD15 and CD11a (presenting 62% of promyelo-metamyelocytes), and in 7/10 cases of primary AMLs that of CD11a, CD11b, CD15, and myeloperoxidase. D1, G1 and F1 induced a dose-dependent inhibition of tritiated thymidine uptake. Apoptosis (evaluated by flow cytometry and agarose gel electrophoresis) was induced in AML blasts by D1 and F1 (79% and 94% respectively for HL 60 cells) and, with less effect, by G1 (27%). The persistence of maturative and apoptotic activity in these new pro-drugs of butyric acid, hydrolysed only inside the tumour cell, suggests a possible use in differentiation therapy of myelodysplastic syndromes and AMLs.

Acute Disease↗

PubMed1998

Pleomorphic adenoma.

Explore the source record for details and available documents.

Adenoma, Pleomorphic↗

PubMed1998

Ewing's family of tumors in adults: multivariate analysis of survival and long-term results of multimodality therapy in 182 patients.

PURPOSE: To assess the outcome and the prognosis of adults with a neoplasm related to the Ewing's sarcoma family of tumors. PATIENTS AND METHODS: The outcomes of 182 consecutive patients older than 15 years with Ewing's sarcoma or related neoplasms managed from 1982 to 1992 were reviewed, without any selection according to primary tumor site or disease extension. RESULTS: Of 182 patients, 53 had evidence of metastases at presentation (29%). Tumor size was greater than 10 cm in 70 patients (41%). With a median follow-up duration of 66 months, the 5-year overall survival (OS) rate was 41%. In patients with localized disease, 5-year OS rate was 54% and 5-year progression-free survival (PFS) rate, 43%. Late relapses after 5 years accounted for 9% of relapses. Metastasis at presentation (P = .00001), pelvic primary lesion (P = .0025), and tumor size greater than 10 cm (P = .004) were independent prognostic factors for survival. Five-year OS was 67% in patients with nonpelvic tumors < or = 10 cm, 52% in those with pelvic tumors less than 10 cm or extrapelvic tumors > or = 10 cm, 16% in those with pelvic tumors greater than 10 cm, and 9% in those with metastasis (P = .00001). CONCLUSION: Based on our experience and a review of the literature, we concluded that the natural history and the prognosis of the Ewing's family of tumors in adults are not different from that found in children. A greater tumor bulk in adults may explain the less favorable prognosis previously reported by others. Outcome could be adequately monitored by a simple prognostic index.

Adolescent↗

PubMed1998

Human papillomavirus genotype as a major determinant of the course of cervical cancer.

PURPOSE: To determine whether the prognosis of invasive cancers of the uterine cervix is related to the type of human papillomavirus (HPV) associated with the tumor. PATIENTS AND METHODS: Two hundred ninety-seven patients with invasive cervical cancer were prospectively registered from 1986 to 1994. HPV typing was performed on DNA extracted from frozen tumor specimens by means of Southern blot hybridization (SBH) and polymerase chain reaction (PCR) techniques. The median follow-up was 38 months. RESULTS: HPV sequences were detected in 246 patients (83%): 150 patients had HPV16, 31 patients had HPV18, and 14 patients had one of the intermediate-oncogenic-risk HPV types (HPV31, 33, 35, 52, 58). In 51 patients, HPV type remained undetermined, and in 51 patients, no viral sequences were found. No significant associations were observed between virologic data and tumor stage or node status. The 5-year disease-free survival (DFS) rate was 100% for patients with intermediate-risk HPV-associated tumors, 58% for patients with HPV16-positive tumors, and 38% for patients with HPV18-positive tumors (P = .02). In multivariate analysis, patients with HPV18-associated tumors had a relative risk (RR) of death 2.4 times greater (95% confidence interval [CI], 1.29-4.59) than that for patients with HPV16, and 4.4 times greater (95% CI, 3.48-5.32) than that for patients with a tumor associated with a viral type different from HPV16/18. CONCLUSION: The prognosis for invasive cancers of the uterine cervix is dependent on the oncogenic potential of the associated HPV type. HPV typing may provide a prognostic indicator for individual patients and is of potential use in defining specific therapies against HPV-harboring tumor cells.

Adult↗

PubMed1998

[Chemotherapy of metastatic cancer of the bladder. Apropos of 50 patients treated with M-VAC].

The most effective chemotherapy of metastatic bladder cancer in M-VAC (methotrexate, vinblastine, cisplatin), as it was shown M-VAC by phase III trials. The complete remission rate is 15-20%. The toxicity is severe, and M-VAC cannot be delivered to fragile patients. Survival is improved. This increase in survival results in an increased incidence in brain metastases. The Cochin Hospital experience with 50 patients treated with M-VAC for a metastatic bladder cancer is presented.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Surgery of lung metastases of breast cancer: analysis of 40 cases

Between 1987 and 1995, 52 breast cancer patients had a surgical resection of lung secondaries. In 40 patients, the diagnosis of metastatic breast cancer could be confirmed following pathological examination. Five-year survival rates of these 40 patients was 54 8 % and 5-year disease free survival was 30 8%. The median survival (70 months) of these patients was better than that of 57 patients with isolated lung metastases who had been treated conservately (chemo- or/and hormonotherapy) during the same time interval. Twenty-six patients benefitted from a radical excision and had a longer disease free interval (42 versus 27 months, p = 0.03) than patients who had had a wedge resection. Overall survival was not significantly different (71 versus 41 months, p = 0.07). We feel that isolated lung nodules may best be treated by radical (segment or lobe) excision, in particular since preoperative differential diagnosis with primary lung cancer may be difficult. In the presence of multiple nodules, first line medical treatment by chemo- or hormonotherapy should be advocated, allowing to reduce the tumor load and to optimize survival in association with surgery.

Journal Article↗

PubMed1998

[Surgical excision of pulmonary metastasis of cancer of the breast: apropos of 40 patients].

Between 1987 and 1995, 52 breast cancer patients had a surgical resection of lung secondaries. In 40 patients, the diagnosis of metastatic breast cancer could be confirmed following pathological examination. Five-year survival rates of these 40 patients was 54 +/- 8% and 5-year disease free survival was 30 +/- 8%. The median survival (70 months) of these patients was better than that of 57 patients with isolated lung metastases who had been treated conservatively (chemo- or/and hormonotherapy) during the same time interval. Twenty-six patients benefitted from a radical excision and had a longer disease free interval (42 versus 27 months, p = 0.03) than patients who had had a wedge resection. Overall survival was not significantly different (71 versus 41 months, p = 0.07). We feel that isolated lung nodules may best be treated by radical (segment or lobe) excision, in particular since preoperative differential diagnosis with primary lung cancer may be difficult. In the presence of multiple nodules, first line medical treatment by chemo- or hormonotherapy should be advocated, allowing to reduce the tumor load and to optimize survival in association with surgery.

Adult↗

PubMed1998

[Complications from the hinged GUEPAR prosthesis after resection of knee tumor. 102 cases].

PURPOSE: The purpose of this study was to present the complications which occurred in knee replacement with the GUEPAR prosthesis, after bone tumor resection. We tried to point out complications in relation to prosthetic design and surgical technique. MATERIAL AND METHOD: Between 1972 and 1993, 90 patients had a knee resection, for 80 malignant and 10 benign tumors. There were 51 males and 49 females, aged 12 to 75 years (mean age 35). Fifty-six distal femur resections and 34 proximal tibial resections were performed. Length of resection averaged 16 cm (9 to 30). The reconstruction was always achieved with a cemented, custom-made GUEPAR prosthesis. Including revisions, there was a total of 102 prostheses in 90 patients. A patellar resurfacing was performed in 64 cases. An allograft reconstruction was associated in 39 knees. In all tibial resections and in two extra-articular femoral resections, the extensor mechanism had to be reconstructed. Several reconstruction techniques were associated, in which 19 medial gastrocnemius transfers. The prosthesis design was slightly modified with time. Ten patients received radiotherapy, and 55 had chemotherapy. RESULTS: Results and complications were retrospectively assessed, with an average follow-up of 4.3 years (1 to 22). Six patients were lost for follow-up, 62 patients were alive, with no evolutive disease, 13 had an evolutive disease and 10 were deceased from disease. Nineteen patients had distant metastasis and 17 had local recurrences. Apart from intraoperative complications, late mechanical complications included: 13 aseptic loosening, 2 femoral shaft fractures, 18 knee contractures, 5 femoral stem fractures and, 18 intra-articular instabilities related to wear of the hinge-axis. In the 39 allograft-composite prostheses, only 15 had a favorable evolution. There were 15 extensor mechanism failures and 13 knees had persistent infection. There was a total of 94 reoperations in the 90 patients. In 28 cases, the initially implanted prosthesis was removed. There were also 18 revisions, 7 amputations and 3 arthrodeses. Survivorship analysis showed a 60 per cent probability for the initial prosthesis not to be revised at 10 year-follow-up, apart from oncologic complications. DISCUSSION: Results with allograft-composite reconstruction were not better than with massive prosthesis. When needed, soft tissue coverage and patellar tendon augmentation would better be performed with gastrocnemius plasty. Polyethylene and steel bushes were not solution for hinge axis wear.

Actuarial Analysis↗

PubMed1997

Phase II trial of doxorubicin, 5-fluorouracil, etoposide, and cisplatin in advanced or recurrent endometrial carcinoma.

We have previously reported an overall response rate of 41% and a median survival duration of 14 months in a series of 49 patients with metastatic or recurrent endometrial carcinoma treated by a combination of etoposide, 5-fluorouracil, and cisplatin. In order to increase response rate and survival duration, doxorubicin was added to this combination. From August 1992 to January 1996, 20 consecutive patients were treated with a monthly combination chemotherapy consisting of doxorubicin 30 mg/m2 i.v. Day 1, 5-fluorouracil 600 mg/m2 i.v. Days 1 to 3, etoposide 80 mg/m2 i.v. Days 1 to 3, and cisplatin 35 mg/m2 i.v. Days 1 to 3 (AFEP). All patients were evaluable for response and toxicity. Median age was 62 years (range 45-72). Two to eight cycles were delivered (median 5). Two of 20 patients had complete response and 7 of 20 had partial response. The objective response rate was 45% (CI 95%: 23-68%). The median survival duration was 17 months. The median progression-free survival was 8 months. Major toxic effect was myelosuppression: 75% of grade 3 and 4 leukopenia and 20% of grade 3 and 4 thrombocytopenia. Seven patients (35%) developed infection and 4 (20%) were hospitalized once or more for toxicity. These results indicate that AFEP is an effective combination therapy in metastatic endometrial carcinoma but its toxicity is unacceptable.

Adenocarcinoma↗

PubMed1997

S-phase fractions of breast cancer predict overall and post-relapse survival.

We studied the correlation of S-phase fraction (SPF) with clinical outcome in 127 pre- or perimenopausal patients with breast cancers treated by neoadjuvant chemotherapy from October 1986 to June 1990. When the patients were analysed using the median value of the SPF as a threshold, there was a small but non-significant difference in favour of low SPF tumours for metastasis-free survival. SPF was the only parameter predicting overall survival in multivariate analysis (P < 0.002) which included T, N, histopathological grade and steroid hormone receptors. The results of metastasis-free survival contrasted with previous analyses with shorter follow-up, so we tested the time-dependent influence of SPF on prognosis. It was thus shown that SPF significantly predicts metastasis-free survival only during the first 30 months, whereas the relative risk of cancer-related death according to SPF remains significant for 56 months. In order to find an explanation for the difference in predictivity between metastasis-free survival and overall survival, we studied the post-relapse survival. Significantly shorter survival (median 12 months) was associated with tumours presenting pre-treatment high SPF values, compared to the low SPF group for which 60% of the patients were still alive after 30 months of metastasis phase (P = 0.002). Our current results, in a homogeneous series with a median follow-up of over 5 years, emphasise the importance of proliferation-related parameters for breast cancer management.

Adult↗

PubMed1997

Docetaxel in combination with doxorubicin or vinorelbine.

The rationale for the development of a new drug combination is to combine optimal doses of drugs with single-agent activity that are not cross-resistant or have similar toxicities. Docetaxel, with its unique mechanism of action and its high response rates in metastatic breast cancer, provides both opportunities and challenges for the development of combination chemotherapy. Anthracyclines are widely accepted as the agents of choice for first-line treatment of metastatic breast cancer and they have been studied in combination with taxoids. Preliminary results with a combination of docetaxel and doxorubicin indicate an overall response rate of 74%, with the dose-limiting toxicities being neutropenia and infection. Vinorelbine also has single-agent activity against metastatic breast cancer and preclinical studies have demonstrated synergism when vinorelbine and docetaxel are combined. The dose-limiting toxicities of the vinorelbine-docetaxel combination are febrile neutropenia and mucositis. The overall response rate to treatment with this combination is 67%. We therefore conclude that docetaxel can be combined with doxorubicin or vinorelbine to provide high response rates and acceptable toxicity.

Antineoplastic Combined Chemotherapy Protocols↗