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P Beuzeboc

Publications and source records attributed to P Beuzeboc.

At least 55 records · Page 3Linked to original sources
PubMed1996

Meningeal carcinomatosis in patients with breast carcinoma. Clinical features, prognostic factors, and results of a high-dose intrathecal methotrexate regimen.

BACKGROUND: This retrospective study evaluates the results of a regimen of high-dose intrathecal methotrexate and the prognostic factors for the response in patients with meningeal from breast carcinoma. METHODS: From 1979 to 1994, 68 breast carcinoma patients were diagnosed with meningeal carcinomatosis at a mean age of 52 years. All but two had previous metastatic involvement. The proportion of lobular and ductal carcinomas was balanced. Malignant cells were present in cerebrospinal fluid (CSF) samples from 61 patients, whereas the 7 remaining patients had increased CSF protein associated with computerized tomographic scan evidence of meningeal metastases. From 1989, 41 of the patients received a regimen of high-dose intrathecal methotrexate with systemic folinic acid rescue (HD-MTX+FA): intrathecal MTX, 15 mg daily x 5 days, repeated every 2 weeks, and intrathecal hydrocortisone acetate, 125 mg on Day 1, and folinic acid, 10 mg intramuscularly 12 hours after each MTX injection. Systemic treatment and radiation therapy were usually associated. Patients treated before 1988 received intrathecal MTX in conventional doses (15 mg once a week). RESULTS: Clinical objective response, defined as a neurological improvement for at least one month, was achieved in 17 patients (41%) and stabilization in 14 (34%) treated with the HD-MTX+FA regimen. The response rate was significantly higher compared with that of the group treated with the conventional doses (P = 0.03). Median survival was 14 weeks for patients treated with the HD-MTX+FA regimen, compared with 7 weeks for patients who received conventional doses of MTX (P = 0.01). Grade 3 or 4 neutropenia was the main toxicity that occurred in 16 16 patients (39%) treated with the HD-MTX+FA regimen, and in 7 patients (33%) treated with conventional doses of MTX. In a univariate analysis, three parameters were singled out as having a favorable prognostic value for response to therapy; controlled systemic disease at diagnosis (P < 0.05), low initial CSF protein level (P < 0.05), and concomitant systemic chemotherapy during intrathecal therapy (P < 0.02). Multivariate analysis was not performed because the sample size was too small. CONCLUSIONS: Although this study was retrospective, the intrathecal HD-MTX+FA regimen appears to be a more efficient strategy than conventional doses of MTX to induce neurologic improvement and perhaps better survival. It should be recommended in combination with systemic chemotherapy for selected patients with meningeal carcinomatosis from breast carcinoma who are likely to benefit from intensive therapy, i.e., patients with a CSF protein level less than 5 g/L and in whom systemic disease has been controlled.

Adult↗
PubMed1996

Sequential assessment of multidrug resistance phenotype and measurement of S-phase fraction as predictive markers of breast cancer response to neoadjuvant chemotherapy.

BACKGROUND: The authors examined the relevance of S-phase fraction (SPF) and multidrug resistance (MDR) phenotype as predictive tests of breast cancer response in a series of patients treated by conventional doses of neoadjuvant chemotherapy with (FAC) or without (FTC) doxorubicin. METHODS: Fine needle samplings of tumors were used to measure SPF by flow cytometry before treatment (Day 0), and to assess the MDR phenotype using semiquantified reverse transcriptase polymerase chain reaction and immunocytochemistry, before and after (Days 8 and 28) the first cycle of chemotherapy. RESULTS: Measurement of SPF before treatment was significantly associated with clinical response, but sequential assessment of MDR phenotype identified three groups of tumors with distinct outcomes: (1) tumors with a positive and constant expression of MDR1, in which prediction of resistance was restricted to patients treated by FAC; (2) tumors without any detectable expression, in which resistance to FAC or FTC treatments was rarely observed; and (3) tumors with an early (Day 8) acquired or increased MDR1 gene expression, which were always resistant to therapy to both treatment regimens. These results were confirmed at the protein level. CONCLUSIONS: Sequential assessment of MDR phenotype is a relevant tool for monitoring breast cancer response in neoadjuvant chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Infiltrating lobular carcinoma of the breast. Clinicopathologic analysis of 975 cases with reference to data on conservative therapy and metastatic patterns.

BACKGROUND: The clinicopathologic features of infiltrating lobular carcinoma (ILC), which represents 5% to 15% of all breast cancers, are still controversial. In particular, the high frequency of multicentric lesions has led to questioning of the effectiveness of conservative treatment for this type of cancer. By studying a large number of cases, we aimed to compare the clinicopathological features of ILC with those of nonlobular infiltrating carcinoma (NLIC) and to assess the advisability of conservative therapy in the management of ILC. METHODS: The population analyzed included 726 cases of ILC, 249 cases of mixed ILC/invasive ductal carcinoma (ILC/IDC), and 10,061 cases of NLIC. The age of patients, TNM status, estrogen- and progesterone-receptor status (ER, PR), and histologic grades of the 3 groups were compared. The follow-up was carried out on a subgroup of 5846 cases. RESULTS: At diagnosis, ILC tumors were found to be larger on average and were detected in patients older than those with NLIC, but the degree of lymph node involvement was lower in patients with ILC than in NLIC. In ILC, tumors are more frequently grade I and ER-positive than in NLIC. Multicentric lesions were not significantly more frequent in ILC than in NLIC. The overall survival, locoregional control, disease free interval, and metastatic spread rates were not different among the three groups neither by univariate nor multivariate analysis, but the pattern of metastatic dissemination was different. In 480 cases of ILC considered for conservation therapy, the local recurrence and overall survival rates were similar to those observed for IDC. CONCLUSIONS: Our analysis specifies the clinicopathological features of ILC and confirms that conservation therapy may be an appropriate treatment for this type of cancer.

Breast Neoplasms↗
PubMed1996

Treatment of advanced or recurrent endometrial carcinoma with combination of etoposide, cisplatin, and 5-fluorouracil: a phase II study.

Forty-nine consecutive patients with metastatic or recurrent endometrial carcinoma were treated with a monthly combination chemotherapy consisting of VP 16-213 80 mg/m2 i.v. Days 1-3, 5-fluorouracil (5-FU) 600 mg/m2 i.v. Days 1-3, and cisplatin 35 mg/m2 i.v. Days 1-3. The objective response rate was 41% (95% CI, 27-54%) with 14.3% complete responses. The median survival duration was 14 months. The median response duration was 12 months. The estimated median survival for responders was 20 months. Three patients are still free of disease 5 years after treatment. The major toxic effects were myelosuppression (less than 25% of grade III and IV leucopenia, and 14% grade III and IV thrombocytopenia). Grade III peripheral neuropathy was observed in five patients. Cisplatin administration had to be stopped due to renal toxicity in six patients. No treatment-related deaths occurred. The combination of etoposide, 5 fluorouracil, and cisplatin is an effective regimen with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.

Adenocarcinoma↗
PubMed1996

Phase II trial of decapeptyl (D-TRP-6), a potent luteinizing hormone-releasing hormone analogue in untreated advanced breast cancer.

Decapeptyl (D-TRP-6), a potent luteinizing hormone-releasing hormone analogue, was administered to 27 premenopausal women with advanced breast cancer; patients were known to have hormone receptor-positive tumors. An overall response rate of 70% was achieved (complete response = 18%, partial response = 52%), with a median time to progression for the whole patient population of 12 months. Toxicity of the schedule was restricted to hot flushes, and the use of a 4-week initial covering period of tamoxifen prevented any flare-up of disease activity from occurring.

Adult↗
PubMed1996

Protracted continuous infusion of 5-fluorouracil in combination with doxorubicin, vincristine, and oral cyclophosphamide in advanced breast cancer.

Several studies suggest that protracted continuous infusion constitutes an important way to optimize the dose and the efficacy of 5-fluorouracil (5-FU) in metastatic cancer. Eighty-three women aged 27-76 (median age 55) with metastatic breast cancer were treated every 4 weeks with a continuous ambulatory venous infusion of 5-FU 350 mg/m2/day and oral cyclophosphamide 100 mg/m2/day over 15 days. The continuous therapy was associated with a weekly administration of vincristine (0.8 mg/m2) and doxorubicin (15 mg/m2) on day 1, day 8, and day 15. Cycles were repeated every 28 days. Thirty-four patients were treated in first-line metastatic chemotherapy and 49 in second-line. Toxicities included: mucositis (grade > or = 2) 23%, diarrhea (grade > or = 2) 7%, a hand-foot syndrome (grade > or = 2) 9%, alopecia (grade 3) 21%, neurological (grade > or = 2) 4%, grade 3 and 4 leukopenia 29%, and grade 3 and 4 thrombopenia 8%. Heart toxicity was only 3%. Catheter infection was observed in 1 case and 7 patients experienced thrombosis. The overall objective response rate (OR) was 48% and the complete response rate was 23%. The median duration of response was 10 months. The median survival was 16 months. Activity was better in naive than pretreated women (respectively, 55% and 42% of OR, p = 0.21). Analysis of responses according to the metastatic sites shows the pronounced efficacy on soft tissue diseases (skin recurrences 42%, lymph nodes 52%), and also in visceral metastases (hepatic 36%, lung 34%).

Administration, Oral↗
PubMed1996

[Severe 5-fluorouracil toxicity in a woman treated for breast cancer with concurrent osteogenesis imperfecta and dehydrogenase deficiency].

Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme involved in the catabolism of 5 fluorouracil (5 FU). The clinical importance of DPD has recently been demonstrated wit the identification of rare cases presenting a severe toxicity to 5 FU related to proven DPD deficiency. We report a new case in a patient with concurrent congenital osteogenesis imperfecta. We were surprised to find another similar association reported by Lyss. It is tempting to speculate that DPD activity may be abnormally regulated in osteogenesis imperfecta patients.

Anemia, Aplastic↗
PubMed1996

Ifosfamide seven-day infusion for recurrent and cisplatin refractory ovarian cancer.

BACKGROUND: The prognosis of advanced ovarian cancer is very poor, with about 15% of patients surviving at five years. Since most of these patients will relapse and/or progress while on therapy, effective salvage treatments are needed. A phase II trial was designed to evaluate the feasibility, toxicity, and response of a seven-day ambulatory continuous infusion of ifosfamide in patients with recurrent or chemoresistant advanced ovarian cancer. PATIENTS AND METHODS: Nineteen patients with progressive ovarian cancer following a cisplatin-based induction chemotherapy were treated with continuous infusion ifosfamide with mesna at 1 g/m2/d and 400 mg/m2/d, respectively, for seven days every 28 days. RESULTS: The overall response rate was 37%. Responses were observed both in patients who relapsed after induction chemotherapy (4/6) and in those who were resistant to cisplatin (3/13). Toxicity was mild and tolerable in these heavily pretreated patients. CONCLUSION: Ifosfamide, when administered as a protracted continuous infusion is an active drug in ovarian cancer and can be safely administered in an out-patient setting. Toxicity is minor even in heavily pretreated patients. Responses are observed in cisplatin refractory ovarian cancer.

Adult↗
PubMed1996

First-line protracted venous infusion fluorouracil with CisDDP or carboplatin in advanced colorectal cancer.

A total of 55 patients with measurable colorectal metastatic carcinoma were studied to evaluate the impact on toxicity, response, and survival of protracted venous infusion (PVI) 5-FU 200 mg/m2 per day with Cis-DDP 80 mg/m2 or carboplatin 300 mg/m2 every 3 weeks, 1-hour infusion. Patients received continuous uninterrupted therapy until there were signs or symptoms of toxicity. Both 5-FU and cisplatin were withheld when patients experienced grade II stomatitis and diarrhea, severe nausea or vomiting not controlled by standard antiemetic therapy, and clinically significant hand-foot syndrome. The toxicity was neurological (20% grade 2 and 3) hematological (13% grade 2) and dermatological (11% grade 2). The overall response (CR+PR) was 24% with a median survival of 13 months. The results of our study show that there is no improvement in response rate, response duration or survival compared with historical trials. However, this study does confirm the valuable palliative role of the protracted 5-FU infusion treatment. Colorectal carcinoma is one of the most common neoplasms in Western societies, being second only to lung cancer as a cause of death from malignancy. The management of nonmetastatic primary disease in surgical, with adjuvant chemotherapy for those at high risk of relapse. However, for those with metastatic disease at diagnosis or recurrent disease after resection, cytotoxic chemotherapy is the treatment of choice and fluorouracil (5-FU) is the most active cytotoxic agent in this disease, with a response rate of approximately 20%. Efforts to improve the response rate have focused on the use of agents to modulate 5 FU. The Southwestern Oncology Group (SWOG) study reported by Leichman et al. (1) and a study from the United Kingdom by Hill et al. (2) compared conventional FU to modulated FU and found no improvement in response rate or survival. In the SWOG study, two different schedules of bolus FU and LV were compared with bolus FU alone and to continuous infusion FU administered alone or modulated by LV or PALA. In this study, the results obtained with bolus FU were superior to most of the studies in the literature: The response rate was 26%, and the median survival was 14 months. The high- and low-dose LV and FU groups showed response rates and survival similar to bolus FU alone. However, in 12 previously reported randomized studies comparing FU and LV or FU alone, nine reported that the combination of FU and LV produced significant increases in response rates and two reported significant increase in survival (3, 4). Many of these trials used the dose schedules reported in the SWOG trial. Protracted venous infusion (PVI) 5-FU has been shown to have superior efficacy with less toxicity in colorectal cancer when compared to bolus 5-FU and synergy between cisplatin and 5-FU has been demonstrated in vitro. Consequently, we have investigated the efficacy of the combination of bolus cis or carboplatin and PVI 5 FU in 55 patients with advanced colorectal cancer using survival, response rate, symptomatic response, and toxicity as study endpoints.

Adult↗
PubMed1995

Breast tumour response to primary chemotherapy predicts local and distant control as well as survival.

The purpose of the present paper was to evaluate correlations between clinical response to chemotherapy and outcome in a subgroup analysis of premenopausal patients with tumours considered too large for breast conserving surgery, treated with primary chemotherapy (n = 200) from a previously published trial (Scholl S.M., Fourquet A., Asselain B, et al. Eur J Cancer 1994, 30A, 645-652). Objective response rates amounted to 65% following four courses. In a multivariate Cox regression analysis, comparing seven parameters, the following variables were associated with poor survival: clinically involved nodes [N1b:RR: 2.7 (95% CI 1.3-5.3)], the failure to respond to chemotherapy [D:RR: 2.62 (95% CI 1.3-5)] and a raised S phase fraction [SPF > 5%: RR: 2.4 (95% CI 1.2-5)]. Parameters associated with increased metastatic recurrence rates, by order of entry in the model, were: young age [< 35: RR: 2.46 (95% CI 1.2-5)], large clinical tumour size [T3: RR: 2.02 (95% CI 1.2-3.4)], poor histological grade (SBR III: RR: 1.93 (95% CI 1.1-3.3)] and the failure to respond to chemotherapy [D: RR: 1.91 (95% CI 1-3.4)]. The assessment of both tumour cell proliferation rates as well as possibly drug resistance markers (although not available in the present study) should be helpful in selecting patients likely to benefit from intensified chemotherapy regimens. The most accurate predictor of response in the present study appeared to be the response to chemotherapy treatment itself.

Adult↗
PubMed1995

Continuous infusion cisplatin and 5-fluorouracil with bolus vinorelbine in the treatment of advanced nonsmall cell carcinoma of the lung.

Thirty-three patients, with histologically proven advanced nonsmall cell lung cancer (NSCLC) were treated at Institut Curie with a three-drug combination chemotherapy. The regimen consisted of cisplatin 25 mg/m2 per day continuous infusion (CI) and 5-fluorouracil (5-FU) CI 600 mg/m2 on 5 consecutive days with 30 minutes infusion navelbine 25 mg/m2 on days 1 and 5 only. Cycles were repeated every 28 days. Response was evaluated after three cycles. One patient died of an ischemic cerebrovascular stroke after the third cycle. Thirty-two pts were evaluable. Partial response was achieved in 11/20 patients with stage III disease (55%) and in 7/12 patients with stage IV disease (58%). WHO grade 4 toxicities were leucopenia 31%, thrombocytopenia 4%, and mucositis 4%. The tolerance was acceptable. Median survival was 19 months for stage III and 9.5 months for stage IV. We conclude that the combination of 5-FU, navelbine, and cisplatin is an effective chemotherapy regimen for patients with advanced stage NSCLC.

Adult↗
PubMed1995

Combined chemoradiation for locally advanced nonsmall cell lung cancer.

We report the results of a phase I study investigating the feasibility of concomitant daily doses of Carboplatin (20 to 25 mg/m2/d over 45 or 10 minutes) and accelerated chest irradiation (60 to 64 Gy over 4 weeks, 2 Gy per fraction, using the concomitant boost technique), alone or following three cycles of induction chemotherapy (cisplatin: 25 mg/m2 per day, d1 to d5, 5-Fluorouracil (5-Fu): 600 mg/m2 per day, d1 to d5, and Vinorelbine: 25 mg/m2 per day, d1 and d5, at 4-week intervals) in 15 patients with locally advanced unresectable nonsmall cell lung cancer. All patients received the planned sequence. The dose-limiting toxicity was esophagitis (5/15 WHO grade 4). No toxic deaths were observed. The tumor response rate was high: 6/15 complete responses and 8/15 greater than 50% tumor regressions. The median survival has not been reached after a mean follow-up of 14 months (range: 6, 28). We are now planning a multicenter phase II study, using the following doses: 20 mg/m2 of daily Carboplatin over 10 minutes and 60 Gy of radiotherapy over 4 weeks.

Adult↗