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T Palangie

Publications and source records attributed to T Palangie.

At least 19 recordsLinked to original sources

ERBB2 overexpression in breast carcinomas: no positive correlation with complete pathological response to preoperative high-dose anthracycline-based chemotherapy.

The predictive value of ERBB2 amplification/expression to doxorubicin use is controversial. Preoperative chemotherapy, followed by the pathological assessment of tumour response to treatment provide optimal conditions for the evaluation of the predictive value of biological parameters. We report here data on the predictive value of ERBB2 in a series of 54 cases of breast cancer treated by preoperative high-dose anthracycline-based chemotherapy. Our series consisted of 26 women presenting an inflammatory breast cancer (IBC) and of 28 women with poor prognosis primary cancer (PPPC). Patients received a total of four cycles with doxorubicin (75 mg/m(2) for IBC or 70 mg/m(2) for PPPC) and cyclophosphamide (6 g/m(2) for IBC or 1400 mg/m(2) for PPPC), every 21 days. ERBB2 expression was determined by immunohistochemistry (clone CB11) performed on a tumour biopsy taken before chemotherapy. All patients underwent surgery as a second step of treatment, and the tumour response was assessed on pathological specimens. A complete pathological response was observed in 24 of the 54 cases (44%) (95% confidence interval (CI), 31-57). Pathological complete response was positively correlated with high histological grade (P=0. 02) and with the absence of oestrogen (P=0.003) or progesterone (P=0. 02) receptor expression. ERBB2 overexpression was found in 18 of the 54 cases (33%). A complete pathological response was observed in 33% of these cases (6/18). This figure was not significantly different from the 50% rate of complete response observed for tumours with no detectable ERBB2 expression (18/36). In this small series, ERBB2 overexpression was not a significant predictive marker of the pathological response to high-dose doxorubicin-based chemotherapy.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

Randomized trial comparing two different modalities of administration of the same cytotoxic drugs in metastatic breast cancer.

This protocol compare the efficacy of continuous infusion fluorouracil (5-FU) with weekly doxorubicin (DOX) and cyclophosphamide (CPM) to a "classical" monthly regimen of the same drugs, as a first line of treatment in metastatic breast carcinoma. The first arm of this protocol consisted of FAC: 5-FU 600 mg/m2 i.v. over 1 hour, day(d) 1, 2, 3, DOX 50 mg/m2 i.v. bolus, d1, and CPM, 400 mg/m2 i.v. bolus, d 1, 2, 3. The second arm consisted of FULON: 5-FU 250 mg/m2 per day continuously infused from d1 to d22, CPM 300 mg/m2 i.v. bolus, d1, 8, 15, 22, and DOX 15 mg/m2 i.v. bolus, day 1, 8, 15, 22. Between January 1990 and June 1993, 258 women with proven metastatic breast carcinoma were randomly assigned either to receive FAC or FULON chemotherapy regimen. Chemotherapy courses were administrated every 4 weeks for FAC regimen and every 6 weeks for FULON. Response rate (54 versus 53%), response duration (14 versus 12 months) and overall survival duration (23 versus 21 months) were not significantly different in the two regimens (FAC versus FULON). Preorative prognostic value of liver metastasis or high LDH level was slightly attenuated in patients treated by FULON. Efficacy of infusional 5-FU in metastatic breast cancer could have been lowered by weekly infusion of doxorubicin in the FULON regimen compared to monthly infusion. According to the modalities of delivery of the drugs, the two regimens seem equally effective.

Adult↗

Prognostic factors in inflammatory breast cancer and therapeutic implications.

223 inflammatory breast cancer patients were diagnosed at the Institut Curie between 1977 and 1987. Patients received chemotherapy and radiation treatment according to three consecutive randomised trials. Five- and 10- year survival rates were 41 and 32%, respectively. Disease-free interval rates were 25.5% at 5 years and 19% at 10 years. Parameters significantly linked with a pejorative prognosis in a multivariate analysis were: diffuse erythema, lymph node involvement, chest wall adherence, and age above 50 years. When therapeutic response parameters were included in the multivariate analysis, the five most important prognostic factors in order of significance were complete tumour regression after completion of induction treatment (at 8 months), complete regression of inflammatory symptoms after 3 months of neoadjuvant chemotherapy, limited erythema at presentation and, less significantly, complete regression of inflammatory symptoms at 8 months and tumour regression at 3 months. In conclusion, patients who achieved a rapid and complete remission had a better prognosis than patients who had an incomplete response to chemotherapy. High-dose chemotherapy and reversal or prevention of drug resistance will be evaluated in future trials. Detailed information on the biology of this disease should allow the design of new strategies aiming to improve patient management.

Adenocarcinoma↗

[Continuous infusion of doxorubicin for 10 days as third-line chemotherapy in metastasized breast tumors. Initial observations].

The authors undertook a study to test the feasibility and efficacy of doxorubicin (Dox) administered as continuous infusion (c.i.) in the treatment of advanced breast cancer patients. All patients were previously treated as first line chemiotherapy with bolus-administered Dox; then they received a second line treatment without Dox. Patients were eligible if they had advanced measurable breast cancer, resistant to first and second line chemotherapy regimens, and if previous Dox treatment had been performed more than one year before, and after ECG and cardiac echographic controls were performed. A dose of 4.5 mg/m2/day of Dox was planned for 10 consecutive days in c.i. through a central venous catheter, repeated at 28 day intervals, for a maximum of 10 cycles. Among the 71 patients, 56 received 3 or more treatment courses; 10 patients refused further therapy after the first cycle. Objective responses were achieved in 25 patients (35%), 3 complete and 22 partial remissions. Stabilization was obtained in 11 patients (16%). The median time to progression was 9.3 months. Obviously, haematological toxicity was the major problem; in the 71 patients, 376 courses were administered (mean number of courses per patient: 5.3): grade 4 neutropenia (WHO system) occurred in 2 patients, and grade 3 in 9 patients; while one patient died of gastric haemorrhage. Severe cardiac toxicity occurred in only one patient who died 24 hours after the beginning of therapy, with ECG lateral ischemia. Grade 4 stomatitis was observed in only one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

[Treatment of cancers of the ovary. Phase II trial of increase of the dose of cisplatin].

Between March 1985 and December 1987, 34 women who had advanced adenocarcinoma of the ovary with macroscopic residual disease entered in a phase II trial of chemotherapy. Treatment consisted of a 3-month induction with monthly ifosfamide combined with 5-fluorouracil and high-dose cisplatin, and a maintenance treatment with ifosfamide, 5-fluorouracil, cisplatin and hexamethylmelamine in monthly cycles. At the end of the treatment patients with complete remission were evaluated by surgery. Neurotoxicity was a limiting factor, and treatment had to be prematurely withdrawn in 10 patients. The above treatment was found to be effective with a 94 percent objective response rate, a 54-month median survival and a 51-month median relapse-free survival. Because of the neurotoxicity, a shorter therapy and the use of neuroprotective agents may be envisaged.

Adenocarcinoma↗

[Malignant epidermoid degeneration of dermoid cysts of the ovary. Apropos of 2 cases].

Malignant transformation of benign ovarian cystic teratomas has been reported in 0.5 to 2% of cases. Many different types of cancer can develop, including squamous cell carcinoma, which is by far the most frequent (75%). The mean age of diagnosis is over 50 years. Minimal surgical techniques have been increasingly popular and laparoscopic removal of benign ovarian cysts has become common practice. Malignant transformation is rare but needs to be recognized in order to avoid dissemination of malignant cells during surgery. Direct invasion of the adjacent pelvic structures and small intestine represents the most common mode of spread. Survival is not improved by post-operative radiotherapy or adjuvant chemotherapy in patients with extracapsular disease. We report two cases, one of which presented with spontaneous ovarian abscess and paraneoplastic hypercalcemia.

Adult↗