Increases in steroid binding globulins induced by tamoxifen in patients with carcinoma of the breast.

The effects of tamoxifen on cortisol binding globulin (CBG) and sex hormone binding globulin (SHBG) were studied in 25 women and one man with breast cancer. These patients were in various endocrine states according to age (15 post-menopausal women) or previous endocrine surgery (ovariectomy, two patients; ovariectomy plus adrenal surgery, five patients; hypophysectomy, three patients; ovariectomy plus hypophysectomy, two patients). The administration of tamoxifen (20-40 mg/day) resulted in increases in the level of CBG in all patients (mean rise in binding capacity 10.8 microgram cortisol/100 ml plasma) and in the level of SHBG in 21 patients (mean rise in binding capacity 0.79 microgram dihydrotestosterone/100 ml plasma for all patients). These increases were positively correlated. They were not associated with any alteration in the association constants of the steroid binding globulins. The effect of tamoxifen on CBG diminished with increasing age. The changes in the levels of CBG and SHBG were independent of the endocrinological state of the patient. It is inferred that tamoxifen has a direct oestrogen-like action on the liver which results in increased production of CBG and SHBG. Tamoxifen therapy for carcinoma of the breast appeared to be least effective in those patients in whom the drug caused the highest increase in the concentration of CBG.

Cisplatinumdiamminodichloride (CPDD) in chemotherapy of cancers: a phase II therapeutic trial.

We have conducted a phase II trial of cisplatinumdiamminodichloride (CPDD) which not only demonstrated its remarkable activity in embryonic carcinoma of the testes, but also in ovarian carcinoma, in melanoma, and in epidermoid carcinoma, especially of the head and of the uterus cervix. Its toxicity, manifested mainly in the digestive and renal tracts, confines its administration to hospitalized patients only. This compound is now indicated in combination therapy for the above-mentioned tumors.

[Chemotherapy of malignant melanoma. Results of a controlled clinical trial comparing vincristine + dacarbazin (DTIC) with and without duborimycin (author's transl)]. / Chimiothérapie des mélanomes malins. Résultats d'un essai contrôlé comparant vincristine et dacarbazine (DTIC) avec ou sans duborimycine.

Adding duborimycin to the association of vincristine + DTIC in the treatment of malignant melanoma produces therapeutic results interesting but not statistically significant and not counter-balancing the toxic side effects. This study confirms the lack of positive results of polychemotherapy in melanoma as compared to treatment by an efficacious single drug therapy (DTIC); it also emphasizes the necessity of randomized studies so that valuable comparisons may be done.

[Polychemotherapy of advanced breast cancer. Triple combination with doxorubicin. Analysis of 209 observation]. / Polychimiothérapie des cancers mammaires en phase avancée. Association ternaire avec doxorubicine. Analyse de 209 observations.

Two hundred and nine patients with breast cancer in an advanced stage were treated according to a chemotherapeutic regimen associating doxorubicin, vincristine and methotrexate, administered in courses of 5 days every three weeks. This analysis deals only with the short range results; they confirm those of a previous randomized study. A global objective response was obtained in 187 cases (89%) and a measurable regression of the lesions in 150 cases (71%); in these later cases 90 (43%) had a regression of more than 50 per cent. The most striking effects, often rapidly observed, involve sites which are not generally sensitive: liver (40%), pleura (24%) and bone (only 6%, but 8 times out of 10 a definite action on the pain syndrome). Side effects were, on the whole, acceptable (only one severe hematologic complication); however, the risk of myocardiac toxocity due to the accumulation of doxorubicin limits the utilization of this association. It thus needs to be relayed by other drug regimens which are included in a program of long term action, but has interesting characteristics as induction chemotherapy.

[Anticancerous chemotherapy trial with duborimycin. Analysis of 151 cases]. / Essai de chimiothérapie anticancéreuse par la duborimycine. Analyse de 151 observations

Duborimycin is a new antimitotic agent approaching danorubicin and adriamycin in activity which has been tried on 151 patients suffering from cancer of different types, is an advanced local/regional stage and/or metastatic disease. It was administered intravenously every fortnight in a mean unit dose of 400 mg, and the duration of the treatment ranged from 2 to 52 weeks. Objective improvement was registered in 56 patients of the 135 cases in whcih the results were assessed (around 41.4% of cases). In 4 cases the regression of tumour volume was greater than 50% (one of these cases was in melanoma, the other a sarcoma) and in 2 cases regression was complete (a squamous cell carcinoma and an embryonal testicular tumour). The subjective effects were appreciable in 53 of the 115 cases which could be studied (46%) and above all in the refractory pain of bony secondaries from breast cancer (a favourable response in 78% of cases). Manifestations of intolerance/toxicity were of a minor nature on the haematologic side, that cardiologic ones relatively frequent (18% of treated cases) and occasionally serious (2 cases of asystole). Great care is therefore necessary in supervision of the treatment. However, the first results obtained by this line of approach, notably in chemo-resistant forms of tumour such as melanoma and sarcomas, utilizing the very strict criteria in one analysis encourage further study of duborimycin in cases of this sort (preferably in association and in accordance with protocols of comparative trials) so that its place in cancer chemotherapy may be more precisely defined.

[Chemotherapy of soft tissues sarcomas. Summary of a decade and current trends]. / La chimiothérapie des sarcomes des tissus mous. Bilan d'une décennie et orientations actuelles

The results of palliative chemotherapy applied to 123 patients with disseminated soft tissue sarcomas are reviewed with the recent literature data. With the exception of embryonal rhabdomyosarcomas of children, which are considered separately, the response of these tumors to chemotherapy is poor but not negligible. The association of several active drugs should permit substantial progress, especially in the initial stage of local treatment, when the number of disseminated cells is still reduced. A follow-up of controlled clinical studies must specify the modalities of multidisciplinary treatment in an effort to reduce regional recurrence or metastasis.

[Survival and prognostic factors in cerebral metastases of breast cancer]. / Survie et facteurs pronostiques dans les métastases cérébrales des cancers du sein.

A number of prognostic factors have emerged from a retrospective study of 83 patients with breast cancer associated with a solid intracerebral tumour (59%), or meningeal invasion (33%) or both (8%). The median survival was 4 months without significant difference between breast tumours and meningeal carcinomatosis. Women in pre-menopause at the initial diagnosis of breast cancer (P less than or equal to 0.05) or who were 50 years of age when the cerebral metastasis occurred (P less than or equal to 0.05) or who had only one metastasis (P less than or equal to 0.02) had a better prognosis. During meningeal carcinomatosis, CSF protein and carcinoembryonic antigen levels have no prognostic value. All patients with intracerebral tumour had been irradiated (40 Gy over 4 weeks). The tumour was removed whenever possible. Intrathecal or systemic chemotherapy and hormone therapy seem to be favourable prognostic factors. This would suggest that chemotherapy may increase the survival of patients with this type of breast cancer, but only randomized studies will demonstrate its true effectiveness.

[Analgesic effects of tiapride in man. A double-blind comparative clinical trial against placebo (author's transl)]. / Etude de l'effet antalgique du tiapride chez l'homme. Essai clinique en double insu: tiapride versus placebo.

A double-blind comparative study to estimate the effects of tiapride when compared to placebo was conducted in 29 patients with pain from cancer. Each patient acted for his own control. Excellent or good results were obtained in 14 cases with tiapride against 6 with placebo, and moderate or no results in 15 patients on tiapride and 23 on placebo. There is a highly significant statistical difference in favour of tiapride for efficacy, but no significant difference was noted between tolerance of tiapride and placebo.

[Controlled study of the analgesic efficacy of 2 drugs: tiapride versus aspirin]. / Etude contrôlée de l'efficacité antalgique de deux médicaments: tiapride versus aspirine.

Analgesic effect of aspirin 500 mg IM or IV and tiapride 300 mg IM or IV was compared in a double blind controlled study. Twenty-four patients with active cancer were each given both drugs successively, over 48 hours. No difference was demonstrated in analgesic effects of tiapride (14/24: 58%) and aspirin (11/24: 46%), or in toxicity which was minor for both drugs.

Stage III non-seminomatous germ cell tumours of the testis--patients treated at the Centre Leon Berard.

The study of the survival of a series of patients with stage III non-seminomatous germ cell tumours of the testis enables us to confirm two points: the use of cis-platinum has multiplied the survival rate for stage III patients by 3, the concept of stage III includes various metastatic states with different prognoses. The use of a sub-classification, like that proposed by Samuels, allows for a better definition of the natural history of these lesions.

The valve of chemotherapy in the treatment of testicular dysembryoplastic tumors.

Chemotherapy appears to be of help in treating dysembryoplastic testicular tumors. It seems better to treat first by surgery (lymphadenectomy) if possible, then (a) if no nodes are involved or only one has been discovered by microscope examination, with chemotherapy for one year; or (b) if two or more nodes are involved, with irradiation of the nodes and chemotherapy. Even if lymphadenectomy is not possible, one course of chemotherapy followed by cobalt and more chemotherapy can bring results in some cases.

[Management of advanced breast cancer in post-menopausal women. A comparative trial of hormonal therapy, chemotherapy, and a combination of both]. / Le traitement des cancers du sein dépassés chez la femme ménopausée. Etude comparative de l'hormonothérapie, de la chimiothérapie et de l'hormono-chimiothérapie.

A randomized trial was done in 98 post-menopausal women with breast cancer. Hormonal receptors had not been assayed in any patient. Patients were given hormonal therapy with tamoxifen and drostanolone propionate (n = 34), or chemotherapy with the CMF protocol (n = 30), or a combination of both (n = 34). The results are in favour of hormonal therapy alone, which gave the best immediate objective responses, the least adverse side-effects, and possibly improved survival rates.

[Operable carcinoma of the breast. Prognostic value of estradiol receptors. Preliminary report (author's transl)]. / Cancer du sein opérable: valeur pronostique du nombre des récepteurs d'estradiol. Rapport préliminaire.

151 women were treated for potentially curable breast cancer. Their tumors were routinely analysed for estrogen receptors by the dextran-coated charcoal technic. Data were analyzed in relation to several parameters: age, age of menstruation, menopausal status, tumor size, TNN staging, axillary node status, nature of treatment. We have examined the pronostic implication of an ER negative content (ER-) in the primary tumor. We have found that the absence of detectable estrogen receptor in primary breast tumor appears to be correlated with a short disease free interval. In positive axillary node patients the value of the disease free interval is significantly shorter in ER- than in ER+ group: 11.5 months versus 23.5 (p less than 0.01).

[Cis-diammino-dichloro-platinum therapy of cancers; phase II therapeutic trial]. / Chimiothérapie des cancers par le cis-diammino-dichloro platinum; essai thérapeutique phase II.

We have conducted a phase II trial of cisdiammino-dichloro platinum (CDDP) which demonstrates its remarkable activity in testis embryonic carcinoma, in ovary carcinoma and in epidermoid cancers, especially head and neck and uterus cervix carcinoma. Its toxicity in mainly digestive and renal. This compound is now indicated in combinations in the case of the above mentioned tumors.