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J Bonneterre

Publications and source records attributed to J Bonneterre.

At least 55 records · Page 3Linked to original sources
PubMed1999

[Aromatase inhibitors].

Aromatase inhibitors used in breast cancer, are drugs that inhibit the transformation of androstenedione and testosterone, respectively in estradiol and estrone. Two classes have been described: steroidal inhibitors which act competitively and irreversibly and non steroidal inhibitors which block the P 450 cytochrome. The first one is aminoglutethimide which has an adrenal effect on 11, 18 and 21 hydroxylase. Rogletimide, less powerful and less specific is a aminoglutethimide analogue. The response rates obtained with formestane is not different. The clinical development has been stopped due to a lack of specificity. Letrozole, vorozole, exemestane and anastrozole are more powerful and more specific. Letrozole and vorozole are at least as efficient and better tolerated than aminoglutéthimide. Anastrozole, letrozole and vorozole are at least as efficient as megestrol acetate and better tolerated in advanced breast cancer patients receiving a second line hormone therapy.

Aminoglutethimide↗
PubMed1998

ERBB2 oncogene in human breast cancer and its clinical significance.

We reveiwed the relationships between ERBB2 amplification and/or overexpression in human breast cancer and the clinicopathological parameters described in the literature (97 studies involving 22,616 patients) in order to draw conclusions regarding its clinical interest. The mean of ERBB2 positivity (26%, ranging from 5 to 55%) is not dependent on the method used to evaluate ERBB2 amplification or overexpression. Despite the discrepancies observed between the different studies, several associations between ERBB2 positivity and the classical clinicopathological parameters were noted. There are clear relationships between ERBB2 positivity and the lack of steroid receptors, the histological subtypes of mammary tumours (ductal invasive and in situ), worse histological and nuclear grades, aneuploidy and high rate of proliferation. In univariate analyses, ERBB2 is strongly associated with poor prognosis. All these data indicate that ERBB2 is a marker of aggressiveness of the tumour. However, ERBB2 does not retain a clinical prognostic significance in multivariate analyses, since it is associated with several strong prognostic parameters. When considering the prognostic value of ERBB2 in relation to treatment, a significantly worse survival of the treated patients is noted in ERBB2 positive patients. This suggest that ERBB2 could be a marker of reduced response to chemotherapy and hormonal treatment. With respect to the tumour response to treatment, the results, provided as yet by pilot studies, remain controversial and further investigations are necessary to evaluate the predictive value of ERBB2. Finally, new therapeutic approaches targeting the cells overexpressing ERBB2 have been developed.

Age of Onset↗
PubMed1998

Plasma insulin-like growth factor in primary breast cancer patients treated with adjuvant chemotherapy.

Insulin-like growth factor 1 (IGF-1) plasma level was assayed in 60 breast cancer patients undergoing six courses of adjuvant chemotherapy. The only observed variation was a slight decrease (10%) in IGF-1 concentrations, assayed before treatment, between the first and the second courses of chemotherapy. During chemotherapy courses, there were no statistically significant variations in IGF-1. These results suggest that chemotherapy, unlike the specific hormonal treatments tamoxifen and somatostatin, certainly does not act via a decrease in plasma IGF-1.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Germline BRCA1 mutations in patients from 84 families with breast and/or ovarian cancers in northern France.

The BRCA1 gene modification is responsible for an autosomal dominant syndrome of inherited early onset breast and/or ovarian cancer. This gene is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about 1 in every 500 women may carry the BRCA1 mutation. The BRCA1 was isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected individuals. Using systematic sequencing, we looked at BRCA1 germline mutations in 84 patients treated at the Centre Oscar Lambret for breast and/or ovarian cancer who belonged to high-risk families. We found 39 mutations: 22 true mutations inducing modifications of the BRCA1 protein (BRCA1+), six mutations with unknown consequences on the BRCA1 protein, and eleven mutations corresponding to polymorphisms that had been described previously. All the BRCA1+ cases had a HPG3 tumour. The median age of discovery and the receptor positivity percentage are lower in hereditary breast cancer than in the standard population of the breast cancers treated in our centre. Conversely, most of the BRCA1+ patients are without node involvement. This shows that BRCA1 mutations are not always related to parameters thought to indicate a bad prognosis.

Adult↗
PubMed1998

The relationship between concentrations of circulating soluble E-selectin and clinical, pathological, and biological features in patients with breast cancer.

Increasing evidence suggests that E-selectin contributes to tumor growth and metastasis. E-selectin may increase tumoral angiogenesis and the adhesion of tumoral cells to endothelial cells at distant sites. The aim of this study was to assess the relationship between concentrations of circulating soluble E-selectin (sE-selectin) and clinical, pathological, and biological features in patients with breast cancer (BC). Concentrations of sE-selectin were analyzed by an ELISA method in sera from 113 patients with metastatic BC, 30 patients with primary inflammatory BC, 105 patients with primary noninflammatory BC, and 42 healthy controls. These concentrations were analyzed in terms of the clinical and pathological features of the tumors as well as in terms of the concentrations of serum inflammatory parameters (erythrocyte sedimentation rate, C reactive protein, interleukin 1 beta, and tumor necrosis factor alpha), the response to chemotherapy or hormone therapy, and the survival duration. Tumoral angiogenesis was also assessed in 68 patients with primary noninflammatory BC who had had primary surgery. The mean concentration of sE-selectin in the metastatic BC group was significantly higher than the mean concentration found in the healthy control group (33.5 versus 21.8 ng/ml; P < 0.01). In metastatic BC, the mean concentration of sE-selectin was significantly higher in patients with liver metastasis than in patients without liver metastasis (55.3 versus 26.0 ng/ml; P < 10(-5). The univariate analysis showed that high concentrations of sE-selectin were associated with reduced overall survival (P < 0.05), but this probably reflected the association between high concentrations of sE-selectin and liver metastasis. In patients with primary noninflammatory BC, a negative correlation was found between sE-selectin concentrations and the tumoral microvessel count (r = -0.47; P = 10(-4). In patients with primary inflammatory or noninflammatory BC, no correlation was found between concentrations of sE-selectin and tumor size, lymph node involvement, response to chemotherapy or hormone therapy, and survival. No correlation was found between the concentrations of sE-selectin and serum inflammatory parameters in any of the patient groups. This study suggests that in patients with metastatic BC, levels of sE-selectin are higher in the presence of liver metastasis. In patients with primary BC, high concentrations seem to be associated with reduced tumoral angiogenesis. Although several studies have previously demonstrated that the expression of cell surface E-selectin enhances the metastatic process, the shedding of sE-selectin in circulation may be considered a mechanism of inhibition of tumor progression.

Adult↗
PubMed1998

Prognostic value of p53 and urokinase-type plasminogen activator in node-negative human breast cancers.

We measured the levels of p53 and urokinase-type plasminogen activator (uPA) in 634 tumor tissues from 634 different node-negative primary breast cancer patients who underwent locoregional surgery in the Center Oscar Lambret between July 1989 and September 1994. p53 and uPA were assayed using commercially available kits in cytosols prepared for estradiol receptor (ER) and progesterone receptor (PgR) assays. The optimum clinical thresholds were chosen for prognostic studies: 4 ng/ml for p53 and 0.5 ng/ml for uPA. p53 was elevated in 13.7% of the tumors, and uPA was elevated in 27.5% of the tumors; they were negatively related (chi 2 test) to ER and PgR and positively related to histoprognostic grading (HPG) and tumor diameter. uPA was negatively correlated to ER and PgR, and p53 and uPA were positively correlated to each other (P = 0.0001; Spearman test). In the prognostic studies, the 316 patients who did not receive adjuvant chemotherapy were included to avoid treatment interference; this number corresponds to all of the patients operated on between 1989 and 1992. The mean duration of follow-up of living patients was 4 years. In overall survival studies, Cox univariate analyses demonstrated a prognostic value of p53 (P = 0.011; risk ratio, 1.59), uPA (P = 0.038; risk ratio, 2.32), PgR, HPG, and tumor diameter. In Cox multivariate analyses, only HPG had a statistically significant prognostic value. In relapse-free survival studies, univariate analyses demonstrated prognostic values of uPA (P = 0.0011) and of age, and both parameters retained their prognostic value in multivariate analyses (uPA: P = 0.0004). This study demonstrates not only that p53 and uPA have prognostic value but also that these two parameters are linked to other classical clinical, histological, or biological prognostic parameters, as well as to each other. Moreover, because uPA is of prognostic value in multivariate relapse-free survival studies, uPA is an important prognostic factor in node-negative breast cancer patients.

Adult↗
PubMed1998

[Granisetron (per os) compared with ondansetron (per os) in the prevention of nausea and vomiting induced by mildly emetogenic chemotherapies. Groupe de Recherches en Cancerologie du Nord].

It is a randomised cross-over multicenter study comparing the efficacy and the tolerance of granisetron (Gra) 1 mg and ondansetron (Ond) 8 mg, oral, given during two consecutive cycles to 188 naive patients scheduled to receive a moderately emetogenic chemotherapy. The antiemetic treatment is given one day per course, 1 hour before chemotherapy and the second administration from 8 to 12 hours after the beginning, during each of the two cycles; alternatively according to the randomisation. Five criteria are assessed; nausea (ordinal and visual analogic scales), emeric episodes (vomiting orland retching), complete response (minor or no nausea, no emetic episode and no rescue treatment), patient preference and tolerance. The intent to treat analysis showed no significant difference at cycle 1 between Gra and Ond; at cycle 2, there is no significant difference in the number of emetic episodes; for the prevention of nausea, the ordinal scale shows a significant difference (p = 0.028 in favour of Gra at day 1 (D1) but not from D2 to D5. Gra induced more complete response than Ond at D1 (p = 0.028), but not from D2 to D5. The cross-over study did not show any period or order effect, whereas a treatment effect on Ond was significant in favour of Gra (p = 0.01). There is no significant patients preference in favour of Gra or Ond. In conclusion, Gra was more efficient in preventing nausea and obtaining complete response on the first day of treatment, significantly at the second cycle. Both Gra and Ond had a good antiemetic activity for moderately emetogenic chemotherapy with complete response rates always over 50% on day 1; delayed emesis remain less weli controlled.

Adult↗
PubMed1998

The development of a French version of a questionnaire on the quality of life in cancerology (Functional Living Index-Cancer: FLIC).

The quality of life has become an indispensable element in the evaluation of treatments, especially as clinical trials are generally conducted in more than one country. In cancerology, numerous questionnaires have been developed and validated, but most of them are in English. This article presents the stages of translation and validation of the French version of the FLIC (Functional Living Index-Cancer). It applies to a sample of 200 patients, 47% of whom have breast cancer. The acceptability of this questionnaire is good (92.2%). The main psychometric criteria were verified. The Cronbach alpha coefficient, equal to 0.90, shows good reliability. A factor analysis was conducted to examine construct validity; it revealed a 5-factor solution accounting for 62% of the variance. These 5 factors are associated with specific domains; physical, psychological and social functioning, current well-being and disease symptoms. The global scores of the FLIC correlate significantly with those of the different scales of the EORTC QLQ-C30. Moreover, clinical relevance is ensured by its correlation with certain clinical variables (WHO index, location of tumour). The French version of the FLIC can be used to measure the quality of life of patients afflicted with cancer, but further studies are necessary to confirm its reliability.

Adult↗
PubMed1998

[Adjuvant treatment of cancer of the breast: cost assessment of the protocol used].

In this study a cost analysis of therapeutics used in the adjuvant treatment of breast cancer has been performed. Four strategies were considered: chemotherapy (FEC, 6 courses), hormone therapy (tamoxifen, 20 mg/day during 3 years), the association of chemotherapy and hormone therapy, or standard follow-up with neither chemotherapy nor hormone therapy. The costs of these strategies were analysed according to the payer's perspective (social security system). In order to complete the economic data, specific investigations were performed at the Centre Oscar-Lambret (COL), a Cancer Center located in Lille (France). The study shows a high cost for chemotherapy (63,767 FF at 5 years) and a high cost for the association (68,891 FF), in comparison to the cost of hormone therapy alone (45,540 FF) or to the follow-up without adjuvant therapy (38,416 FF). These costs could be confronted to the efficacy data of these different strategies and to the cost of avoided relapses. Cost-effectiveness and cost-benefit ratios of these adjuvant strategies could then be assessed.

Breast Neoplasms↗
PubMed1997

Effectiveness of cold cap in the prevention of docetaxel-induced alopecia.

Docetaxel is a new taxoid antineoplastic agent with clinical efficacy especially in breast cancer. One of the most distressing side-effects induced by docetaxel is alopecia. We studied the prevention of alopecia by using a cold cap in 98 patients receiving 100 mg/m2 docetaxel by 1 h i.v. infusion every 3 weeks. One patient was lost to follow-up. 83 patients (86%) were evaluated as a success to the cold cap, as they presented WHO grade alopecia < or = 2 and no need to wear a wig. 14 patients (14%) had to wear a wig; among them; 7 patients withdrew before the evaluation at three cycles. The cold cap is a very effective technique with minimal side-effects for docetaxel-treated patients.

Adult↗
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

Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy.

PURPOSE: To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients. PATIENTS AND METHODS: Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function. RESULTS: Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern. CONCLUSION: CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.

Adult↗
PubMed1997

Phase I studies of combined paclitaxel/epirubicin and paclitaxel/epirubicin/cyclophosphamide in patients with metastatic offast cancer: the French experience.

In an attempt to develop new, active, and convenient outpatient combination-chemotherapy regimens for patients with metastatic breast cancer, we performed two phase I studies combining paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus anthracycline for the first-line treatment of metastatic disease, without the use of hematopoietic growth factors. Study I was designed to test the tolerability and antitumor activity of a 3-hour infusion of paclitaxel in combination with an epirubicin intravenous bolus. Study 2 explored a three-drug chemotherapy regimen: a 3-hour paclitaxel infusion with epirubicin and cyclophosphamide. Courses were repeated every 3 weeks. If any dose-limiting events occurred in two or more of six patients in the first course of a given dose level, that dose level was defined as the maximum tolerated dose. Dose-limiting criteria included the following: neutrophils less than 0.25 x 10(9)/L lasting for > or = 5 days, any febrile neutropenia, World Health Organization grade 4 thrombocytopenia, World Health Organization grade > or = 3 nonhematologic toxicity or grade > or = 3 mucositis for more than 5 days, and absence of hematologic recovery at day 35. In both studies, paclitaxel doses were escalated in subsequent groups of three to six patients. For study I, the initial dose level consisted of paclitaxel (110 mg/m2)/epirubicin (50 mg/m2). To date 40 patients have entered the study at eight dose levels. Of the 181 cycles evaluated, grade 3 or 4 neutropenic episodes were observed in 63% of courses, with only five episodes of febrile neutropenia. Grade 2 or 3 neurotoxicity was observed in 43% of patients. Two patients experienced clinical heart failure. The dose-limiting toxicity has not been reached so far. At dose level 7 (paclitaxel [250 mg/m2]/epirubicin [50 mg/m2]), only one patient of six experienced febrile neutropenia. We are currently testing paclitaxel (200 mg/m2)/epirubicin (75 mg/m2). Preliminary evaluation of response documents two complete and 16 partial responses in 37 evaluable patients (48% overall response rate). In study 2, the initial dose level consisted of paclitaxel (150 mg/m2)/epirubicin (50 mg/m2)/cyclophosphamide (500 mg/m2). To date, three dose levels have been investigated in 16 evaluable patients (82 cycles). Grade 3 or 4 neutropenic episodes were observed in 80% of courses, and five episodes were associated with neutropenic fever. Grade 2 neurotoxicity was observed in 28% of patients. The dose-limiting toxicity has not been reached, and we are currently investigating dose level 4 (paclitaxel 225 mg/m2). These trials confirm the tolerability of combined paclitaxel/epirubicin and paclitaxel/epirubicin/cyclophosphamide. The antitumor activity is encouraging.

Adult↗
PubMed1997

[Germ-line mutation of BRCA1 in patients with breast and/or ovarian cancer in high risk families in Northern France].

The BRCA1 gene modification is responsible for an autosomal dominant syndrome of inherited early onset breast and/or ovarian cancer. This gene is estimated to account for almost half of inherited breast cancers and three quarters of inherited breast/ovarian cancers. This suggests that about 1 out of 500 women may carry BRCA1 mutation. The BRCA1 gene was isolated by positional cloning in 1994. More than 100 different mutations have been found in the germline of affected individuals. We looked by systematic sequencing at BRCA1 germline mutations in 36 patients treated at the Centre Oscar-Lambret for breast and/or ovarian cancer and that belonged to high risk families. We have found 24 mutations: 9 true mutations inducing modifications of the BRCA1 protein (BRCA1+), 5 mutations with unknown consequences on the BRCA1 protein and 10 mutations corresponding to polymorphisms that had been previously described. All the BRCA1+ cases had a HPG3 tumor. The median age of discovery and the receptor positivity percentage are lower in hereditary breast cancer than in the standard population of the breast cancers treated in our center. Consequently, BRCA1 mutations are associated to parameters thought to be of bad prognosis.

Adult↗
PubMed1997

[Medico-economical assessment in cancerology].

In recent studies, the economic criteria has begun to be integrated to the appraisal in cancerology. The question asked by the economist can be framed as follows: what incremental cost should the collectivity or the health insurance system consent, in order to improve the care of cancer patients? This involves first that the cost of the strategies, foreseen or already implemented, can be appraised, then, that indicators can be defined to capture health improvement, and finally, that this health improvement can be quantified. In this article, we present the process of integrated appraisal (cost/result approach). We specifically analyze costs in cancerology, their source and their evolution. We demonstrate the meaning of the integration of economic costs and medical results. We emphasize on the fact that part of the costs, especially those supported by the patient and his close relations, are most of the time excluded from the analysis. Two main points should be carefully analyzed, when proceeding to an appraisal in cancerology: the measurement of the patient's QoL, which represents an expression of the results of the strategy of care; the financing modalities, for the same type of care, if we consider the specificity of the structures involved and the organization of the care. We conclude by mentioning how difficult this task is and under which conditions it should be developed.

Cost of Illness↗
PubMed1997

[A medico-economic evaluation of second line chemotherapy in metastatic breast cancer: comparison between docetaxel, paclitaxel, and vinorelbine].

Despite health public problems arised by metastatic breast cancer, specific studies remain rare, and especially when concerning second line chemotherapy. Today, these studies seem essential to allow the clinician, facing the choice between different treatments, to make the best decision. Two recent treatments, docetaxel and paclitaxel, administered every 3 weeks, were compared to the referenced treatment: vinorelbine administered every week. The study aims at evaluating these 3 therapeutic options on second line treatment of metastatic breast cancer. For each of these 3 strategies, our end points were: (1) the duration of progression free survival; (2) the quality adjusted on progression free survival; (3) the cost including the intrinsic cost of chemotherapy as well as the cost of treatment-related and disease-related complications, due to toxicity. Savings obtained with the treatment by delaying relapse were subtracted from expenditure. We used a Markov model to describe the patient's evolution after the administration of the compared treatments. The evaluation concerns the period from the beginning of second line chemotherapy to death. Only direct medical costs were taken into account. Non medical costs and indirect costs were excluded. For each clinical state, resources utilisation was estimated by a retrospective multicentric analysis of 153 medical records of metastatic breast cancer, treated on second line. Resources valuation of hospital costs were based on a national survey on the cost of medical services per DRGs. Quality of life was estimated by a group of nurses in oncology, using the feeling thermometer and standard gamble technics. Incremental cost utility ratios were calculated. Docetaxel reduces the time spent in progression, decreases the number of complications due to progressive disease and thereby provides better quality of life. It provides a benefit of 57 disease- and discomfort-free days, compared to vinorelbine and 22 days compared to paclitaxel. Docetaxel may be thought of as a self-financing strategy as a result of savings in hospital admissions, providing net saving of French Francs (FF) 6,800 in 1993 prices, compared with expenditure associated with vinorelbine treatment and FF 700 compared with the equivalent figures for paclitaxel. A sensitivity analysis confirms the robustness of those results.

Aged↗
PubMed1997

[Progestational agents and bone metastasis in breast cancer].

Hormonotherapy in metastatic breast cancer is actually performed using 3 therapeutic classes: antiestrogen as tamoxifen (TAM), progestins, megestrol acetate (MA) and medroxyprogesterone acetate (MPA), aromatase-inhibitors as aminoglutethimide (AG). We investigated therapeutic efficacy of progestins compared to other hormonotherapies in case of breast cancer with bone metastasis. In a literature review, we found ten randomized trials comparing: MPA versus AG, MPA versus MA, MPA versus TAM, MA versus AG versus TAM. The results show an advantage on the response rate using MPA; the usual dose was 900-2,000 mg daily. MPA mode of action can explain these results since they combine gestagenic, androgenics and glucocorticoid effects.

Aminoglutethimide↗