[Hepatic metastases of breast cancer. Analysis of the parameters which influence the response to chemotherapy]. / Métastases hépatiques de cancer du sein. Analyse des paramètres qui influencent la réponse à la chimiothérapie.

In a serie of 759 patients treated for metastasized cancer of the breast, presence of an hepatic focus was observed in 29 percent of cases. Isolated hepatic metastases were found in 4 percent of cases while in 25 percent they were associated with other tissues. At the time of initial clinical staging, the difference between the hepatic metastases group and the other group stems from the much greater frequency of severity indices in the former group indicating a general and biological transformation of the metastatic tumor(s). At therapeutic staging, the slight effectiveness of medical therapies can be accounted for by the slight tolerance among patients with a secondary hepatic tumor(s). Lastly, it is interesting to note that progesterone receptor presence does not modify the prognosis in hepatic metastases cases.

[Metastatic breast cancer: controlled trial of chemotherapy with and without hormones]. / Cancer métastasé du sein: essai contrôlé de chimiothérapies avec et sans hormones.

Two hundred and twenty-three patients with disseminated breast cancer entered in a randomized trial: Group I: 130 patients were given a monthly 5 day- course of a cytotoxic chemotherapy protocol including Adriamycine, Vincristine, Cyclophosphamide, 5 Fluoro-uracile (A.V.L.F.); Group II: 93 patients were given alternatively the same program and a non cross resistant program including: VM 26, Mitomycine C, Methotrexate (V.M.M.). The patients of these groups were randomized into three subgroups: Subgroup O: chemotherapy alone; Subgroup N: chemotherapy + Tamoxifen (20 mg/m2/day); Subgroup NN: chemotherapy + Tamoxifen + Norethisterone (40 mg/m2/day). Objective response rates to cytotoxic chemotherapy were respectively of 65 per cent and 68 per cent in groups I and II of chemotherapy. Further more mean-duration of response and survival were not different. Objective response rates were comparable in the three subgroups of chemo-hormonotherapy. However, the survival was significantly better in the subgroup N (with Tamoxifen) when compared with the subgroup O (without hormonotherapy), and marginally better (p = 0,09) when compared with the NN subgroup (with Tamoxifen + Norethisterone).

The value of a radioimmunological monitoring in cancer patients treated with interferon alpha.

Using a radioimmunoassay for human leukocyte interferon (IFN alpha), pharmacokinetic studies were carried out in twelve cancer patients given sequential intramuscular injections of Hu IFN alpha 2. Even though individual monitoring of serum IFN titers emphasized, for a given dose, marked quantitative variations of the observed maximum concentrations, their mean values were found to be dose-dependent (358 +/- 167 U/ml at 30.10(6) U and 1044 +/- 599 U/ml at 100.10(6) U doses). Comparison with bioassay results showed that IFN activities measured in sera were of the same order of magnitude as those calculated from radioimmunoassay standard curves. Data obtained from this series on observed peak time, half-life value and serum concentrations were consistent with those reported by the other groups using recombinant leukocyte interferon in clinical trial. Therefore, radioimmunoassay is an useful method for routinely assaying IFN alpha used either as antitumour or antivirus agent because of its high sensitivity (4 U/ml) and its simplicity.

[Phase-1 study of the tolerance for increasing doses of recombinant human alpha 2 interferon in patients with advanced cancer]. / Essai phase l' de tolérance à des doses croissantes d'interféron recombinant human alpha 2 chez des patients porteurs de cancers avancés.

Thirteen patients with malignant tumors were entered into a phase I trial with recombinant DNA human alpha 2 interferon (IFN alpha 2). The patients were given I.M. escalating doses of IFN alpha 2 ranging from 1-10(6) to 200-10(6) IU with a 72 hours washout between injections. In the majority of the patients, subjective symptoms were noted: fever, headache, chills, nausea, myalgias. Asthenia, anorexia, drowsiness appeared after the highest doses and disappeared without any sequellae. Leucopenia and thrombopenia were seen in 11 out of 13 patients. Hepatocellular toxicity was observed in 9 cases. Cardiac and vascular functions were not impaired by IFN alpha 2. The pharmacokinetic studies showed a maximum serum concentration between 4 and 6 hours after injection and the peak value was directly proportional to the dose. No neutralizing INF alpha 2 serum factor was detected during the treatment. The peak value for serum beta 2 microglobulin occurred 48 hours after and the N.K. activity was variably modified by IFN alpha 2 injections. A major clinical response was observed in 1 case, a minor response in 3 cases and a stabilisation of the disease in 4 cases.

[Metastatic breast cancer: a comparative study of the efficacy of tamoxifen and the sequential administration of tamoxifen and medroxyprogesterone acetate]. / Cancer du sein métastasé: étude comparée de l'efficacité du tamoxifène et d'une administration séquentielle de tamoxifène et d'acétate de médroxyprogestérone.

Seventy-nine patients with an histologically proven disseminated breast cancer, never treated before with additive hormonal therapy, entered into a randomized trial between june 1981 and december 1982. In the first group 44 patients were given continually a daily dose of tamoxifen (TAM) of 20 mg/m2. In the 2nd group 35 patients were given a daily dose of TAM of 20 mg/m2 for 15 days and then an oral daily dose of medroxyprogesterone acetate of 350 mg/m2 for the next 15 days. In both groups I and II, the treatment was stopped at the first manifestation of progression of the disease. The hormonal receptor status was determined in 30 patients of the group I and 23 patients of the group II. An objective response to treatment was observed in 48 per cent of the patients of the group I and 60 per cent of the group II. This difference is not significant (X2 = 1,05). However, the mean duration of therapeutic response is significantly higher in the group II (p = 0,01).

[Metastatic breast cancers: comparison of the prognostic significance and the sensitivity to chemotherapy according to the presence of estradiol and progesterone receptors]. / Cancers mammaires métastasés: comparaison de la signification pronostique et de la sensibilité à la chimiothérapie selon la présence de récepteurs d'oestradiol et de progestérone.

102 patients with disseminated breast cancer entered this retrospective study. An estrogen receptor (ER) assay was realized in 91 patients and a progesterone receptor (PgR) assay in 90 cases; 44 per cent of the patients were considered as ER+ and 29 per cent as PgR+; 56 per cent were considered as ER- PgR-. The objective response rate to cytotoxic chemotherapy after 4 months of treatment was 66 per cent for ER-, 73 per cent for ER+, 67 per cent for PgR- and 74 per cent for PgR+. However, the mean duration of response was significantly shorter for ER- patients, and no difference appeared between PgR+ and PgR- patients. The acturial survival curves demonstrated a favorable prognostic significance of ER+ as compared to ER- p = 0,03), but the difference was slightly more significant for PgR+ as compared to PgR- (p = 0,008). The prognostic significance of PgR in patients with advanced breast cancer treated with cytotoxic chemotherapy does not appear to be related to the sensitivity to this treatment.

[Ovarian adenocarcinoma stage III and IV treated by a combination of adriamycin, cyclophosphamide, 5-fluorouracil and cis-DDP. Therapeutic role of cis-DDP in this combination]. / Adénocarcinomes de l'ovaire stade III et IV traités par une association d'adriamycine, cyclophosphamide, 5 fluoro-uracile et cis-DDP. Rôle thérapeutique du cis-DDP dans cette association.

Seventy-one patients with advanced ovarian carcinoma (stage III and IV) were included in this study between october 1977 to june 1981. Surgical resection was initially judged impossible in 17 cases, partial in 38 and complete in 16 cases. Forty-seven patients (group A) were given a monthly course of a three drug combination including adriamycin (ADM: 40 mg/m2 day 1), cyclophosphamide (CPM: 400 mg/m2 on days 2, 3, 4), 5 fluoro-uracile (5 F.U.: 600 mg/m2 on days 2, 3, 4). Twenty four patients (group B) were given the same drug combination plus cis-DDP (80 mg/m2 on day 4). After failure of the treatment in group A, 20 patients received the same combination chemotherapy as in group B (group C). The overall response rate of treatment was comparable in both groups A and B: 62 per cent (29/47) in group A including 32 per cent of complete clinical responses (15/47), 66 per cent in group B (16/24) including 33 per cent of complete clinical responses (8/24). The median of survival was 24 months in group A and 21 in group B. Twenty per cent (4/20) of the patients in group C had an objective response to cis-DDP after failure of the combination of adriamycin-cyclophosphamide-5 fluoro-uracile. The quality of initial surgical resection, the size of non resectable tumors and the clinical response to treatment appear as parameters of significant prognostic value.