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P Beuzeboc

Publications and source records attributed to P Beuzeboc.

At least 37 records · Page 2Linked to original sources
PubMed2000

[How to finance chemotherapy with new cancer drugs?

Recently developed drugs are ten to one hundred fold more costly than the chemotherapies of the past while the number of eligible patients and the average duration of treatments are ever increasing. The combined effect of these trends makes budgeting a daunting task, in particular for hospitals with budgetary allocation. Balancing budgets became difficult with the arrival of taxanes, but innovative therapies based on biotechnological advances will further increase the financial slide. Hospital running costs can not be infinitely reduced. Therefore, new rules that govern the financing of innovative therapies become mandatory and budgetary allocations based on DRG evaluations will no longer be feasible.

Antineoplastic Agents↗
PubMed1999

Neoadjuvant chemotherapy in young breast cancer patients: correlation between response and relapse?

The aim of this analysis was to assess how the clinical response to chemotherapy corresponded to long-term prognosis in patients of less than 35 years of age. A retrospective analysis was made of response and survival data of 609 premenopausal patients who had been treated by four cycles of neoadjuvant chemotherapy followed by surgery and/or radiotherapy. Patients were stratified into three age groups (group 1, < or = 35 years; group 2, 35-40 years; group 3, > or = 41 years). Objective and complete clinical response rates were significantly higher in the youngest patients (below 35 yrs: P = 0.005 and P = 0.001, respectively) in stark contrast to a particularly poor outcome of this subpopulation. Five-year local recurrence rates were 31% in the youngest patients, compared with 26% and 16% in groups 2 and 3, respectively (P = 0.0007). Group 1 patients also had significantly higher 5-year metastatic relapse rates (41% versus 35% and 28%; P = 0.007) and 5-year survival figures were 70%, 82% and 84% for groups 1, 2 and 3 respectively (P = 0.002). Finally, stratification by age and by response revealed that, whilst the outcome of the youngest patients was highly dependent on their response to primary chemotherapy, complete responders showed disease-free survival rates at 5 years that were lower than these of older patients, whatever their response. Despite a seemingly better control of the primary tumour by chemotherapy, the patients in the youngest age group remained at a high risk for local and metastatic relapse. This apparent paradox may be in part attributable to rapid disease progression of micrometastatic tumour subpopulations that are refractory to chemotherapy.

Adult↗
PubMed1999

Dose-finding study of docetaxel and doxorubicin in first-line treatment of patients with metastatic breast cancer.

PURPOSE: To determine the maximum tolerated dose (MTD), the dose-limiting toxicity (DLT) and the recommended dose of docetaxel in combination with doxorubicin, and to evaluate the activity in patients with advanced breast cancer. PATIENTS AND METHODS: Forty-two women with untreated metastatic breast cancer (79% with visceral metastases; 52% with prior adjuvant anthracycline therapy) were treated with doxorubicin (40-60 mg/m2) i.v. bolus followed one hour later by docetaxel (50-85 mg/m2) one-hour i.v. infusion every three weeks, without G-CSF support. RESULTS: The MTD occurred at the dose level combining 85 mg/m2 of docetaxel and 50 mg/m2 of doxorubicin, with the DLT being neutropenic sepsis. Neutropenia and/or its complications were manageable and no grade 3-4 or severe non-hematological toxicities were observed. Fluid retention was frequent but never severe. With a median cumulative dose of doxorubicin of 392 mg/m2 (240-559 mg/m2) and a median follow-up time of 29 months (9(+)-41), no congestive heart failure was observed. High activity was observed at all dose levels, particularly the last four, with a response rate of 81% (95% confidence interval (95% CI): 62.5-92.5). Median time to progression was 46 weeks (6(+)-62). Two-year survival was 66%, and median survival has not yet been reached. CONCLUSIONS: Docetaxel-doxorubicin is feasible, safe and highly active. The incidence of febrile neutropenia without G-CSF requires careful monitoring but is acceptable in this setting. There does not appear to be an increase in the cardiac toxicity of doxorubicin. The recommended doses is either docetaxel 75 mg/m2 and doxorubicin 50 mg/m2 or docetaxel 60 mg/m2 and doxorubicin 60 mg/m2, administered every three weeks.

Adult↗
PubMed1999

[Herceptin, a monoclonal humanized antibody anti-HER2: a major therapeutic progress in breast cancers overexpressing this oncogene?].

HER2 is overexpressed in about 25% to 30% of breast cancers and associated with poor prognosis, resistance to hormonotherapy and lack of sensitivity to CMF-based adjuvant chemotherapy. Herceptin (trastuzumab), a humanized monoclonal antibody, administered as a single agent, produces objective responses in phase II trials in patients with metastatic breast cancers overexpressing HER2. It has shown a substantial benefit in a phase III trial which compares a standard first line chemotherapy (doxorubicin and cyclophosphamide or taxol alone) to the same chemotherapy with Herceptin in metastatic breast cancer. The Herceptin arm had significantly higher response rate (+ 53%), an improvement in the median duration of response (+ 57%) as well as in time to progression (+ 65%) compared to chemotherapy alone.

Antibiotics, Antineoplastic↗
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

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

High incidence of brain metastases in patients treated with an M-VAC regimen for advanced bladder cancer.

OBJECTIVE: We report on central nervous system metastases from urothelial bladder carcinoma in patients treated with M-VAC chemotherapy. METHODS: 50 patients with advanced transitional cell carcinoma of the bladder were treated with the M-VAC regimen at the Hôpital Cochin (Paris, France) between December 1989 and February 1995. Brain relapses were diagnosed by CT scanning. RESULTS: We observed a surprising increase in the number of central nervous system relapses (8/50) in patients treated consecutively at the same institution. The mean time to metastatic recurrence in the brain from the initiation of first chemotherapy was 21 months (range 7-38). Six patients had single and 2 patients had multiple central nervous system metastases. Treatment consisted of radiotherapy alone (n = 5) or both surgery and radiotherapy (n = 3). Median survival time from the appearance of cerebral metastases was 3 months (range 1-10). CONCLUSION: The prolonged duration of remissions which are achieved following M-VAC chemotherapy may explain the greater likelihood of the detection of cerebral involvement.

Aged↗
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

[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

[Urothelial tumors of the bladder].

Bladder cancer is a common malignancy and accounts for 8,000 new cases and 4,000 deaths each year in France. Numerous factors may be responsible for the development of this disease, first of which are smoking and occupational exposure to chemicals. Main data regarding etiology, epidemiology and biology of bladder cancer are detailed. Diagnostic and therapeutic advances as well as actual research directions are presented.

Humans↗
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

IL-6 is a survival prognostic factor in renal cell carcinoma.

It has been reported that a high plasmatic concentration of interleukin-6 (IL-6) is correlated to a lack of response to immunotherapy in several malignancies, suggesting that IL-6 was either a marker of tumour aggressiveness or had only a predictive value of response to immunotherapy. To discriminate between these two possibilities, a retrospective study was performed in a series of 19 patients with metastatic renal cell carcinoma who did not respond to IL-2/IFNalpha/5-FU treatment. Serum levels of IL-6, C-reactive Protein (CRP), soluble IL-2-receptor (sIL-2R), M-CSF and neopterin were assayed before treatment. IL-6 showed a significant correlation with patients median survival time (P < 0.016), suggesting that serum concentration of IL-6 before treatment is a marker of tumour aggressiveness rather than a predictive parameter for an immunological response.

Adult↗
PubMed1997

[A combined radiochemotherapy trial for non-small cell lung cancers: initial results].

PURPOSE: Analysis of the preliminary results of a phase I study investigating the feasibility of concomitant chemotherapy with daily doses of carboplatin (20 to 25 mg/m2/d over 45 or 10 min) and accelerated chest irradiation (60 to 64 Gy over 4 weeks, 2 Gy per fraction, using the concomitant boost technique). MATERIALS AND METHODS: This combination was given alone or following three cycles of induction chemotherapy (cisplatin, 25 mg/m2 per day from d1 to d5; 5-fluorouracil, 600 mg/m2 per day from d1 to d5 and vinorelbine, 25 mg/m2 per day at d1 and d5 with a 4-week interval) in 15 patients with locally advanced unresectable non-small cell lung cancer. All patients received the planned sequence. RESULTS: The dose-limiting toxicity was esophagitis (5 out of 15 grade 4). No toxic deaths were observed. The tumor response rate was high: six out of 15 complete responses and 14 out of 15 tumor regressions greater than 50%. The median survival was not reached after a mean follow-up of 14 months (range, 6-28 months). CONCLUSION: We are now planning a multicenter phase II study using the following combination: 20 mg/m2 of daily carboplatin over 10 min and a 60-Gy irradiation dose over 4 weeks.

Adult↗
PubMed1997

Plasminogen activator inhibitor-1 (PAI-1) is not related to response to neoadjuvant chemotherapy in breast cancer.

There is no information available on the relation between response to chemotherapy and the high-risk phenotype assessed by uPA and/or PAI-1. The clinical situation of neoadjuvant chemotherapy provides a means of rapidly assessing the sensitivity of the primary tumour to cytotoxic drug regimens. The goal of the study was to assess prospectively the predictive value of PAI-1 for response to first-line chemotherapy. PAI-1 concentration was measured on hypertonic cytosolic extracts (0.4 M potassium chloride) by ELISA before chemotherapy on a drill biopsy sample of the tumour in 69 T2 and T3 breast cancer patients (median age 46 years). Oestrogen receptor (ER) (51% ER+), progesterone receptor (PR) (58% PR+), S-phase (median 4.0%) and ploidy were also assessed in the majority of cases. The clinical response to treatment was evaluated after four cycles of FAC or FEC regimen (5-fluorouracil, epidoxorubicin or doxorubicin and cyclophosphamide) (one cycle every 4th week). PAI-1 could be assayed in 29 post-chemotherapy surgical samples. The objective response rate (complete response plus partial response) was 59% (41 out of 69). PAI-1 expressed as gram of tissue (range 19-2370 ng g(-1) tissue) was highly correlated (r = 0.98) to PAI-1 expressed as mg protein (range 0.5-68 ng mg(-1) protein). No correlation between PAI-1 level and response could be observed, with any cut-off. The post- and pre-chemotherapy PAI-1 levels were correlated (r = 0.66). Of all biological parameters, only high S-phase (cut-off 5%) was slightly correlated (chi2 = 3.91, P = 0.05) to response. These data suggest that PAI-1 is not a predictive marker of response to chemotherapy in breast cancer and that its level is not altered by neoadjuvant chemotherapy.

Adult↗