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Biomedical subjects

R Paridaens

Publications and source records attributed to R Paridaens.

At least 55 records · Page 3Linked to original sources
PubMed1997

Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimide: a phase II multicentre multinational study. Exemestane Study Group.

In a European multicentre phase II study, 80 postmenopausal patients (pts) with advanced breast cancer progressing on aminoglutethimide (AG) at daily doses of > or = 500 mg were enrolled. Seventy-eight received exemestane (200 mg daily orally), including 33 pts resistant to prior AG, 39 pts who had progressed after an initial response to AG, and 6 pts whose response to AG was either unavailable or not evaluable. Three pts were pretreated with AG only, 69 with tamoxifen and AG, and 6 with tamoxifen, AG and other hormone therapies; 55% had also previously received chemotherapy. The predominant site of disease was visceral in 34 cases, bone in 27 and soft tissue in 17. Based on Peer Review assessment, the overall objective response rate (CRs plus PRs) was 26% (12% in pts resistant to AG and 33% in AG-responsive pts). Disease stabilisation > or = 24 weeks was achieved in an additional 13% of patients (15% of those resistant to AG and 13% of those AG-responsive), resulting in an overall success rate of 39% (28-50, 95% confidence interval). The median duration of objective response, overall success and median TTP were 59, 48 and 21 weeks, respectively. Toxicities were usually mild to moderate in severity, with hot flushes (21%), nausea (19%), dizziness (12%), weakness (12%), increased sweating (12%), androgenic symptoms (10%) and peripheral oedema (9%) as the most common side-effects. Only 2 pts (3%) discontinued treatment due to adverse events. These results are very promising considering that exemestane was administered as third- or fourth-line hormonal treatment in most cases and confirm previous observations about the lack of cross-resistance when steroidal aromatase inhibitors are sequenced with the non-steroidal aromatase inhibitor AG.

Aged↗
PubMed1997

EORTC phase II study of daily oral linomide in metastatic renal cell carcinoma patients with good prognostic factors.

Following a previous EORTC GU-Group study, in which linomide showed some activity in poor prognosis patients, this study was initiated to determine the effect of linomide in more favourable patients. 35 patients with metastatic renal cell carcinoma with good prognostic factors, i.e. good performance status, prior nephrectomy, no prior systemic therapy, and no liver, bone or brain metastases, were treated with linomide, a quinoline derivative with immunomodulating properties, at a dose of 10 mg daily, after an initial dose escalation during the first 4 weeks of treatment. In 29 evaluable patients, no responses were observed (95% confidence interval 0-10%). Best overall response was no change in 9 patients, for a median duration of 4 months. Linomide in this schedule was poorly tolerated, with 17% (6 patients) of patients being withdrawn and 23% (8 patients) having dose reductions due to adverse events, mostly influenza-like symptoms of myalgia, arthralgia and fatigue. Several cases of pericarditis and neuropathy were observed. In spite of selection of favourable prognosis patients and an optimal daily dosing schedule, linomide was not an effective treatment in renal cell carcinoma. In view of toxicity and lack of efficacy, there is no rationale in further testing the drug in this disease.

Antineoplastic Agents↗
PubMed1997

Corticosteroids significantly delay the onset of docetaxel-induced fluid retention: final results of a randomized study of the European Organization for Research and Treatment of Cancer Investigational Drug Branch for Breast Cancer.

PURPOSE: To confirm the efficacy of docetaxel in patients with breast cancer previously treated with one chemotherapy regimen for advanced or metastatic disease and to compare the incidence of fluid retention (FR) and skin toxicity when docetaxel is administered with and without prophylactic corticosteroids. PATIENTS AND METHODS: Eighty-three patients, pretreated with one chemotherapy regimen for metastatic breast cancer (MBC) with bidimensionally measurable and progressive disease, were eligible for this randomized trial. Docetaxel with prophylactic oral antihistamine was administered at a dose of 50 mg/m2 as a 1-hour infusion on days 1 and 8 every 21 days and patients were randomized to receive methylprednisolone (40 mg days -1, 0, 1, 7, 8, and 9 of each cycle) (arm A) or no methylprednisolone (arm B). RESULTS: Twenty-eight patients (34%, 95% confidence interval [CI], 23% to 45%) achieved on objective response. The median time to disease progression and median overall survival time were 5 and 13.5 months, respectively. In total, 415 cycles of docetaxel were administered (arm A: N = 219, median = six; arm B: N = 196, median = five). The most common toxicity observed was grade 3 or 4 neutropenia, which occurred in 79% of patients. Clinically significant nonhematologic side effects included skin reactions and asthenia. In an intent-to-treat analysis, patients who received methylprednisolone premedication had a delayed onset of FR (median time to onset of FR: arm A, 84 days; arm B, 62 days; P = .01) and received a higher median cumulative dose of docetaxel before the onset of FR (arm A, 333 mg/m2; arm B, 215 mg/m2; P = .001). There was no statistically significant difference in the incidence of skin toxicity between the two arms. CONCLUSION: Docetaxel, at this dose and schedule, has definite antitumor activity in pretreated MBC patients. Moreover, this is the first randomized trial to show that corticosteroids have a favorable impact on docetaxel-induced FR.

Adult↗
PubMed1997

Maximal androgen blockade versus total androgen suppression.

As long as advanced prostate cancer remains androgen-dependent, it can be treated by castration in combination with anti-androgens. When despite maximal androgen blockade (MAB), progression occurs, the anti-androgen withdrawal can result in partial remission. Otherwise corticosteroids can be used in low doses in order to suppress the androgens originating from the adrenal gland: total androgen suppression (TAS). The minimal side effects and the low cost price of this treatment are important advantages, given the fact that only few efficient cytostatic agents are actually available for hormone-escaped prostate cancer. About 30% of the patients with advanced prostate cancer that became androgen independent will show a secondary remission under low doses hydrocortisone or prednisone.

Adenocarcinoma↗
PubMed1997

Exemestane experience in breast cancer treatment.

Exemestane is a very potent, orally active, selective and long-lasting steroidal irreversible inhibitor of aromatase. It is 150 times more potent than aminoglutethimide (AG) in inhibiting human placental aromatase (Ki of 4.3 and 671 nM, respectively). The compound is presently under phase III evaluation in Europe and the U.S.A. for the treatment of postmenopausal advanced breast cancer (ABC). Clinical pharmacology studies have been carried out with single doses ranging from 0.5 to 800 mg and repeated doses of up to 600 mg a day, in 132 postmenopausal healthy volunteers and in 185 postmenopausal women with ABC. Results obtained using a very specific and sensitive analytical method (high performance liquid chromatography-radioimmunoassay; HPLC-RIA) indicated that exemestane is extremely effective in inhibiting plasma estrogens levels. Estrogen inhibition is clearly evident at 5 mg a day and maximal suppression for E2, E1 and E1S (>85%, >90% and >90%, respectively) is obtained at 10-25 mg a day. Data from non-controlled phase II studies involving more than 400 patients indicated a clear anti-tumour activity in postmenopausal ABC patients failing multiple hormonal treatments. In 62 patients progressing on AG (> or = 500 mg a day) exemestane treatment resulted in an objective response rate of approximately 24%; disease stabilization > or = 24 weeks was observed in an additional 24% of cases. With regard to safety, although daily doses up to 600 mg were administered, the maximal tolerated dose was not achieved; reported symptoms were mainly related to the pharmacological action of the compound and were usually mild to moderate in severity, resulting in the discontinuation of therapy in less than 3% of cases. In conclusion, the available results suggest that exemestane treatment is associated with minimal toxicity, and may be of significant benefit for ABC women who have exhausted conventional therapy.

Androstadienes↗
PubMed1996

Characterisation of complete responders to combination chemotherapy for advanced breast cancer: a retrospective EORTC Breast Group study.

This retrospective study was undertaken to characterise the natural history of women achieving complete response (CR) following standard dose combination chemotherapy for metastatic breast cancer (MBC), and to analyse the significance of various patient, disease and treatment characteristics in determining survival and time to disease progression. 75 patients achieving a CR following standard dose combination chemotherapy or combined chemoendocrine therapy for MBC have been studied. At a median follow-up of 6 years, 28% of patients are still alive, with 18 of 21 patients showing no evidence of disease. 15 (20%) patients, with median follow-up of 61 months from start of chemotherapy, have never experienced relapse. Median overall survival is 32.5 months. Multivariate analysis for survival identified inclusion of anthracyclines and WHO performance status as significant predictors of good long-term outcome. Concomitant hormonotherapy almost reached statistical significance in our multivariate analysis. Neither dominant site of disease nor disease-free interval were significant determinants of complete remission. With conventional dose combination chemotherapy, approximately 20% of women with MBC who have achieved a clinical CR have been shown to be expected to remain alive and free of disease at 5 years. Inclusion of an anthracycline appears to be an important determinant of durability of CR and patient survival.

Adult↗
PubMed1996

Phase II clinical trials with rhizoxin in breast cancer and melanoma. The EORTC Early Clinical Trials Group.

Rhizoxin is a new anti-tumour agent isolated from the pathogenic fungus Rhizopus chinensis. It has shown broad activity against murine tumour models and is also active against vinca alkaloid-resistant cells. The purpose of our studies was to determine the clinical activity of this compound in patients with advanced breast cancer and melanoma. Based on the results of a phase I study, 2.0 mg m-2 was administered as intravenous infusion over 5 min every 21 days. Nineteen patients were entered into the breast cancer phase II trial and received a total of 50 courses (median 2, range 1-6). Of these, dose reductions were performed in three courses because of leucopenia or stomatitis (1.5 mg m-2, one course; 1.45 mg m-2, two courses). Twenty-six patients were entered into the melanoma trial and received a total of 70 courses (median 2, range 1-12). No dose reductions were required. All patients were eligible for toxicity. Haematological toxicity included neutropenia CTC grade 3 (29/120 courses, 24.2%) and grade 4 (11/20 courses, 9.2%). Only drug-related CTC grade 1 thrombocytopenia was observed. Non-haematological toxicity included alopecia in all patients after two courses of treatment as well as CTC grade 3/4 stomatitis and asthenia. In the breast cancer study, one patient achieved a more than 50% tumour reduction after six cycles but was progressing after 6 weeks. Another patient showed a partial remission after the first course but was taken off the study because of CTC grade 3 skin toxicity. One patient was not evaluable for response (early death). No objective remissions were observed in 15 evaluable patients. In melanoma, no objective remissions were observed. We conclude that rhizoxin can be safely administered at 2.0 mg m-2 every 3 weeks. However, it has little activity in patients with advanced breast cancer and melanoma.

Adult↗
PubMed1996

Case study of quality assurance in the administration of chemotherapy.

The purpose of the study was to monitor the quality of chemotherapy administration within the department of oncology, of the university hospitals in Leuven (Belgium), by focusing on prescription and documented administration of chemotherapy. First, the actors and phases of the process were identified. Then selected patient records of three different types of chemotherapy were retrospectively analysed for 453 chemotherapy administrations. Study results indicated an important need to standardize the nursing and medical guidelines concerning chemotherapy administration. A formal task force was established to work on a multidisciplinary basis. The goals were to improve the routine process by identifying practical problems at any level and to standardize procedures by replacing all poorly defined "habits" by well-structured guidelines.

Antineoplastic Agents↗
PubMed1996

An ongoing European organization for research and treatment of cancer crossover trial comparing single-agent paclitaxel and doxorubicin as first- and second-line treatment of advanced breast cancer.

The activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in advanced breast cancer patients who have failed doxorubicin treatment is well established, but the optimal sequence between these two important agents remains to be determined. The European Organization for Research and Treatment of Cancer therefore designed a prospective randomized clinical trial in which patients not exposed to anthracyclines in the adjuvant setting received either first-line paclitaxel, given as a 3-hour infusion at a dose of 200 mg/m2 followed at the time of disease progression by second-line doxorubicin, given as a bolus injection at a dose of 75 mg/m2 or the reverse sequence. The target accrual is 330 patients. Interim results on 207 evaluable patients of 289 randomized are presented.

Adenocarcinoma↗
PubMed1995

Therapy-related acute myeloid leukemia with t(8;16)(p11;p13) following anthracycline-based therapy for nonmetastatic osteosarcoma.

A case of therapy-related AML with t(8;16)(p11;p13) 14 months following the end of anthracycline-containing chemotherapy for a nonmetastatic osteosarcoma of the left tibia is presented. The patient was successfully treated with intensive remission-induction chemotherapy. Subsequently, he underwent an uncomplicated allogeneic bone marrow transplantation from his HLA-identical brother and is at present alive and disease-free 10 months after diagnosis of the secondary AML.

Acute Disease↗
PubMed1995

An EORTC pilot study of filgrastim (recombinant human granulocyte colony stimulating factor) as support to a high dose-intensive epiadriamycin-cyclophosphamide regimen in chemotherapy-naive patients with locally advanced or metastatic breast cancer.

BACKGROUND: In an attempt to increase chemotherapy dose intensity by step-wise reduction of the time interval between treatment cycles, filgrastim was administered to breast cancer patients receiving a three-month combination chemotherapy with epirubicin (E) and cyclophosphamide (C). PATIENTS AND METHODS: Chemotherapy-naïve patients with locally advanced or metastatic breast cancer received fixed doses of E (120 mg/m2) and C 9830 mg/m2) by 15-min i.v. infusion on day 1 of each cycle and filgrastim at a dose of 4 micrograms/kg once daily by SC injection starting 24 hours after chemotherapy. Cohorts of patients were treated in successive schedules, each schedule corresponding to a specified time interval between chemotherapy cycles. The toxicity observed in each schedule was evaluated before patients were accrued to the next schedule, which corresponded to a shorter time interval between chemotherapy cycles. RESULTS: The maximum tolerated schedule was E (120 mg/m2) plus C 9830 mg/m2) given every 14 days with filgrastim support from day 2 until day 13. On this schedule, 5 of 12 patients experienced dose-intensity-limiting toxicities (DLT) during the 3-month study period. Non-hematological DLT occurred in 2/12 patients (mucositis, skin toxicity) while /312 experienced febrile neutropenia requiring i.v. antibiotics. All patients achieved recovery of ANC to >1.5 x 10(9)/l by the time of scheduled retreatment. The combination of filgrastim with this regimen did not seem to add major toxicities. The efficacy was high, with 87% of patients achieving an objective response and a median response duration of 18 months (range: 4-52 months). CONCLUSIONS: Filgrastim permits at 33% increase in 'EC' dose intensification over that of the conventional every-3-week administration. Randomized studies should now be initiated to evaluate the merit, if any, of 'accelerated' chemotherapy in advanced breast cancer.

Adult↗
PubMed1995

Interim results on a randomized trial of mitomycin C in combination with orchidectomy for newly diagnosed metastatic prostate cancer.

The interim results of a randomized trial comparing orchidectomy alone versus orchidectomy and mitomycin C in 178 newly diagnosed metastatic prostate cancer patients are presented. Of 148 evaluable patients 75 were treated with orchidectomy alone and 73 received adjuvant intravenous mitomycin C. Mean time to progression was 15 months in the orchidectomy group versus 14 months in the mitomycin C group. Interim analysis did not demonstrate a favorable effect of the combination with this chemotherapeutic agent compared to orchidectomy alone (P = .45).

Aged↗
PubMed1994

Docetaxel (Taxotere) in advanced malignant melanoma: a phase II study of the EORTC Early Clinical Trials Group.

The antitumour activity of docetaxel was investigated in patients with advanced malignant melanoma. Docetaxel, 100 mg/m2, intravenous, over 60 min, was administered every 3 weeks. Response evaluation was performed after two cycles. No prophylactic treatment with steroids or antihistamines was given. 38 patients were included, 36 were eligible and evaluable for toxicity and 30 patients were evaluable for response. The main haematological toxicity was neutropenia [17 patients with common toxicity criteria (CTC) grade 4 and 11 CTC grade 3] with nadir after 5-8 days and rapid recovery. The most frequent non-haematological toxicity was generalised alopecia (83% of the patients). Asthenia, malaise and fatigue were also seen in 58%. Skin toxicity was also frequent. Hypersensitivity reactions (erythematous rash, urticaria, blood pressure changes and tachycardia), seen in 42% of the patients, were mild to moderate. Oedema was registered in one fifth of the patients and developed after four or more treatment cycles. The overall response rate in the evaluable patients was 17% (five partial responders). We conclude that docetaxel has activity in advanced malignant melanoma.

Adult↗
PubMed1994

Docetaxel (Taxotere) in advanced renal cell cancer. A phase II trial of the EORTC Early Clinical Trials Group.

Docetaxel (Taxotere), an analogue of paclitaxel, was tested in a phase II study in advanced renal cell carcinoma. Consenting patients with measurable lesions, adequate organ functions and no prior chemotherapy received 100 mg/m2 of docetaxel as a 1-h infusion every 3 weeks. No premedication to avoid hypersensitivity reactions or nausea and emesis was given. 32 eligible patients received 100 treatment cycles. Short-lasting neutropenia was the dose-limiting toxicity. Acute hypersensitivity reactions (HSR), oedema and skin changes were other important side-effects. HSRs regressed spontaneously or were treated with antihistamines with or without corticosteroids. One partial remission was documented. At the dose and schedule used, docetaxel has only low activity against renal cell carcinoma.

Adult↗