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A 76 year-old man with urothelial carcinoma of the bladder presented marked leucocytosis (69,300 mm3) and hypercalcemia (15.4 mg/mm3). The paraneoplastic origin of these observations was demonstrated. The authors review other reported cases and discuss the pathogenic factors and the mechanisms of this paraneoplastic association.

The current study reports the results of Adriamycin (doxorubicin), etoposide, and cyclophosphamide (AVE) in small cell bronchogenic carcinoma. The overall rate of response was 82% in patients with limited disease and 66% in patients with extensive disease; complete remissions have been achieved in 20% of the patients with limited disease and in 7% of those with extensive disease. The median duration of survival was 14 months in patients with limited disease and 8.3 months in those with extensive disease. The results, and the analysis of literature, suggest that survival rather than response should be used to compare studies of chemotherapy in small cell bronchogenic carcinoma.

The endocrine response to prolonged dexamethasone treatment was investigated in six postmenopausal women with generalized mammary carcinoma. Plasma cortisol levels decreased rapidly and became undetectable whereas significant concentrations of plasma dehydroepiandrosterone and androstenedione persisted throughout the study, even in two ovariectomized patients, indicating a certain degree of autonomy or a greater resistance of adrenal 'androgens' to the inhibition of ACTH secretion. Except in the ovariectomized patients, plasma testosterone did not fall significantly whereas the plasma oestrogens tended progressively towards undetectable concentrations. A similar response was found in six normal postmenopausal women although the disappearance of their oestrogens was relatively rapid. This indicates that much of the testosterone present after the menopause could still be produced by the ovaries whereas the ovarian production of oestrogens becomes negligible. The delayed disappearance of oestrogens in the patients with mammary carcinoma indicates that the persisting adrenal 'androgens' remained efficient precursors of oestrogen synthesis within the peripheral tissues and presumably within the mammary tumour itself. Plasma dihydrotestosterone behaved like the plasma oestrogens. Despite the fall in plasma oestrogens, plasma gonadotrophins did not increase further but plasma prolactin rose progressively. The persistance of steroid sex hormones and the rise of plasma prolactin might explain the poor response to dexamethasone treatment in mammary carcinoma.A prolonged suppression of the adrenal cortex was produced by giving dexamethasone to 6 postmenopausal women with generalized mammary carcinoma. Plasma cortisol levels decreased rapidly while plasma dehydroepiandrosterone and androstenedione persisted. Plasma testosterone did not fall, except in ovariectomized patients. Plasma estrogens gradually decreased. This slow disappearance of estrogen indicated that persisting adrenal androgens continued to be precursors of estrogen synthesis in peripheral tissues, and possibly within the tumor tissue also. Plasma dihydrotestosterone estimations were similar to those of plasma estrogens. Plasma gonadotropins remained the same. Prolactin increased gradually. Since the growth of mammary carcinoma in postmenopausal women may be partially under endocrine control and the hormones involved are the sex hormones, and possibly prolactin, the persistence of sex hormones and rise of plasma prolactin may be why dexamethasone produces only a minimal response.

The single agent activity of chlorozotocin was evaluated in advanced colorectal cancer not previously treated with chemotherapy. The drug was given at a dosage of 200 mg/m 2 i.v. repeated every 6 wk . Of 23 evaluable patients, 2 achieved a partial response lasting 4 and 5 months respectively. With this dosage regimen, chlorozotocin produced essentially nausea and vomiting in one-half of the patients as well as myelosuppression that varied with performance status. Our findings suggest that the therapeutic index of chlorozotocin is similar to that of other conventional nitrosourea derivatives in this disease. However, additional experience is needed to definitely assess how cumulative is their respective bone marrow toxicity.

One hundred and twelve patients with small cell lung cancer (SCLC) were treated with a combination (CAVE) of cisplatin ( 60 mg/m 2 day 1), adriamycin ( 45 mg/m 2 day 1), etoposide ( 80 mg/m 2 days 1-2-3) and cyclophosphamide ( 1 g/m 2 day 1) given every 4 weeks. A total of 10 courses were given. Response evaluation was initially evaluated after the first two courses of CAVE and repeated at least after treatment completion. This regimen was associated with severe hematological toxicity, mainly leucopenia; five toxic deaths related to sepsis were observed. One hundred and one patients were evaluable for response: 63 with limited disease and 49 with extensive disease. Overall complete and partial response rates after the first two courses of chemotherapy were 16% and 63% respectively but 14 late complete responses were documented, leading to a 30% total complete response rate; 38% in patients with limited disease and 19% in those with disseminated disease. Median overall survival was 46 weeks with a 17% 2 year survival. The only significant prognostic factor for survival was the type of response. There was no survival difference between ‘early’ and ‘late’ complete responders. Complete responders had a 75 week median survival time with a 34% 2 year survival. CAVE is thus an effective regimen for SCLC, but with a considerable toxicity.

Chemotherapy with a combination of cisplatin (60 mg/m2), Adriamycin (45 mg/m2), and etoposide (120 mg/m2 X 3) (CAV) has been evaluated in 36 patients with small-cell bronchogenic carcinoma (SCBC) after two full courses. The complete response (CR) rate was 23% in patients with extensive disease and 64% in patients with limited disease; the partial remission (PR) rate was 59% in patients with extensive disease and 22% in those with limited disease after two cycles (six weeks) of therapy. Patients with CR survived significantly longer than patients with PR (P = 0.02). Side effects were acceptable and consisted mostly of nausea, vomiting, alopecia, and myelosuppression. Thirteen patients were included into a "late intensification" program that was performed with increased doses of CAV regimen used for remission induction. This intensification of chemotherapy was carried out in a protective environment and with autologous bone marrow transfusion. In two patients with PR, CR could be obtained after late intensification and in one patient whose disease was progressing, PR had been achieved. However, excessive extramedullary toxicity of the late intensification regimen, consisting of mucositis, suggested that CAV does not appear to be the optimal therapy for further intensification.

The predictive significance of quantitative assessment of estrogen receptors in tumor tissue was analyzed in women with advanced breast carcinoma. Receptor concentration was measured by the 3H-estradiol binding capacity of the cytosol fraction of biopsies taken before initiation of the treatment. The E. O. R. T. C. criteria for the assessment of the patients' response were used. In a total of 34 assessments, 25 biopsies contained receptors; the remaining ones were negative. Objective remission to various endocrine therapies was recorded in only eight of the receptor-positive patients. Responses occurred along the whole scale of receptor concentrations with an apparent crowding in the region of the higher values. Linear logistic regression analysis revealed that among 12 variables of known prognostic value, receptor concentration was the most significant in relation to therapeutic response. Other significant variables were bone involvement and age. Computations yielded formulas that are presented in graph form and provide an estimate of the probability of a given patient to respond to endocrine treatments. On the other hand, the results suggest that all patients are possibly hormone dependent, although to variable degrees. The latter concept has very definite therapeutic implications.

In a prospective randomized trial comparing CMF to CMF + HD-MPA for primary node positive breast cancer patients, the authors evidenced clear improvement of hematological tolerance (especially of WBC - granulocytes counts) to chemotherapy in the group receiving also hormonotherapy. The design of the trial allowed to give the patients overall high doses of CMF therapy in both arms; in the group receiving HD-MPA significantly higher doses of CMF could be administered (96.3-97.8% for CMF + HD-MPA treated patients vs 89.7-91.1% for CMF alone treated patients). The menopausal status did not influence the results.

A phase II clinical trial of high-dose cisplatin (120 mg/m2 iv every 3 weeks), with fluid and mannitol-induced diuresis, was conducted in 81 patients with advanced lung cancer. Partial remissions were documented in 26% of 75 evaluable cases for a median duration of 3.5 months. Adenocarcinoma and small cell anaplastic carcinoma were more responsive than epidermoid carcinoma, with partial response rates of 35%, 30%, and 18%, respectively. The median survival of responders (8.5 months) was significantly longer than the survival of nonresponders (4 months) (P less than 0.02). Myelosuppression was mild. Renal toxicity with peak serum creatinine greater than 2.5 mg/100 ml occurred in eight patients, with one death occurring due to toxicity. Cisplatin is an active drug in advanced lung cancer.

Long-term results of 2 studies combining etoposide and adriamycin with cisplatin (CAV) or cyclophosphamide (AVE) in small cell lung cancer indicate a 2-year survival rate of 22% and 18% respectively. The complete response rate 2 years after the onset of chemotherapy was 8% (8/98) : 11% (4/36) with CAV and 5% (4/62) with AVE. Among these 8 patients, 2 had a late relapse and one died of an unrelated cause. The actual long-term survival rate was 6% with CAV and 5% with AVE.

Tissue samples from 166 primary and 136 metastatic breast cancers were analysed for the presence of estrogen receptors. It was found by measuring the affinity of the cytoplasmic fraction of these samples for 3H-estradiol-17 beta that receptors were present in 72 p. 100 and 54 p. 100 of primary and metastatic cancers respectively. Receptor concentration varied among sample in an apparently continuous distribution from zero to 2,080 femtomoles per mg tissue protein. This suggests that mammary tumors are different from one another more in a quantitative than in a qualitative way. Detectable amounts of receptors were found in samples from mammary dysplasia, fibroadenomas as well as from one papilloma; none was detected in samples from non-tumorous mammary gland, nipple areola or skin. At mastectomy, no correlation was found between presence or absence of receptors in the primary tumors, and presence or absence of metastatic axillary nodes. On the other hand both the primary and its axillary metastases almost always displayed the same characteristic as far as presence or absence of receptors was concerned. Analysis of clinical studies reported seems to indicate that women with advanced breast cancer respond in a fair proportion of cases to various endocrine treatments when tumor tissue biopsies contain estrogen receptors whereas the probability of a response is very low in their absence.

Liver function tests, liver scintigraphy and peritoneoscopy were carried out in 240 patients with carcinoma. Hepatic invasion was demonstrated by peritoneoscopy essentially when both of the other tests were positive. However, in one-third of the patients, peritoneoscopy revealed the presence of other pathologic changes which could account for the positivity of either of the other diagnostic procedures. The status of the liver, with regard to presence or absence of metastases, could be microscopically documented in 59 patients. False-negative findings of liver chemistry tests, liver scan and peritoneoscopy were seen in 27, 42 and 36 per cent, respectively, of the patients while the rate of false-positive results was 15, 10 and 3 per cent, respectively. The rate of false-negative peritoneoscopy examinations in the absence of simultaneous positivey of the two other investigations was insignificant. These data indicate that liver chemistry tests, liver scan and peritoneoscopy play a major and complementary role in the screening of patients with carcinoma.

Summary Etoposide and cis -platinum combination was used in 87 patients with bronchogenic squamous-cell carcinoma or adenocarcimona. The overall response rate was 41% with 4 complete responses. In patients with loco-regional disease who had not received any prior anticancer therapy, the response rate was 59% (19/32) with 3 (10%) complete responses, significantly higher ( P =0.002) than that observed in the other patients (31%). Overall, responding patients survived significantly longer ( P = 0.001) than nonresponders (median survival 63.3 weeks vs. 23.0). Toxicity was tolerable; gastrointestinal side effects were occasionally responsible for discontinuation of therapy and sepsis was the cause of death in 2 neutropenic patients. No serious nephrotoxicity was observed. The combination of etoposide and cis -platinum should probably be tested in combination with surgery or radiotherapy.

The predictive significance of quantitative assessment of estrogen receptors in tumor tissue was analyzed in women with advanced breast carcinoma. Receptor concentration was measured by the 3H-estradiol binding capacity of the cytosol fraction of biopsies taken before initiation of the treatment. The E. O. R. T. C. criteria for the assessment of the patients' response were used. In a total of 34 assessments, 25 biopsies contained receptors; the remaining ones were negative. Objective remission to various endocrine therapies was recorded in only eight of the receptor-positive patients. Responses occurred along the whole scale of receptor concentrations with an apparent crowding in the region of the higher values. Linear logistic regression analysis revealed that among 12 variables of known prognostic value, receptor concentration was the most significant in relation to therapeutic response. Other significant variables were bone involvement and age. Computations yielded formulas that are presented in graph form and provide an estimate of the probability of a given patient to respond to endocrine treatments. On the other hand, the results suggest that all patients are possibly hormone dependent, although to variable degrees. The latter concept has very definite therapeutic implications.

The current study reports the results of Adriamycin (doxorubicin), etoposide, and cyclophosphamide (AVE) in small cell bronchogenic carcinoma. The overall rate of response was 82% in patients with limited disease and 66% in patients with extensive disease; complete remissions have been achieved in 20% of the patients with limited disease and in 7% of those with extensive disease. The median duration of survival was 14 months in patients with limited disease and 8.3 months in those with extensive disease. The results, and the analysis of literature, suggest that survival rather than response should be used to compare studies of chemotherapy in small cell bronchogenic carcinoma.

Chemotherapy with a combination of cisplatin (60 mg/m2), Adriamycin (45 mg/m2), and etoposide (120 mg/m2 X 3) (CAV) has been evaluated in 36 patients with small-cell bronchogenic carcinoma (SCBC) after two full courses. The complete response (CR) rate was 23% in patients with extensive disease and 64% in patients with limited disease; the partial remission (PR) rate was 59% in patients with extensive disease and 22% in those with limited disease after two cycles (six weeks) of therapy. Patients with CR survived significantly longer than patients with PR (P = 0.02). Side effects were acceptable and consisted mostly of nausea, vomiting, alopecia, and myelosuppression. Thirteen patients were included into a "late intensification" program that was performed with increased doses of CAV regimen used for remission induction. This intensification of chemotherapy was carried out in a protective environment and with autologous bone marrow transfusion. In two patients with PR, CR could be obtained after late intensification and in one patient whose disease was progressing, PR had been achieved. However, excessive extramedullary toxicity of the late intensification regimen, consisting of mucositis, suggested that CAV does not appear to be the optimal therapy for further intensification.

After initial surgery, 240 pre-, peri- or postmenopausal patients with early node-negative breast carcinoma were randomized to receive either no hormone therapy or adjuvant therapy with medroxyprogesterone acetate at high dosage (HD-MPA; 500 mg IM per day times 28 or 500 mg intramuscularly (i.m.) 5 days a week for 5 weeks then 500 mg i.m. twice weekly for the 5 following months. After a median follow-up time of 3 years, relapse-free survival and overall survival appeared significantly improved in the HD-MPA arm. Side effects were tolerable.