Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.

Between November 1, 1983 and June 30, 1987, 510 node-positive, estrogen receptor (ER)-positive breast cancer patients have been randomly allocated to receive either chemotherapy (six intravenous [IV] cyclophosphamide, methotrexate, and fluorouracil [CMF] courses followed by four IV epirubicin courses) or 5 years of tamoxifen treatment or a combination of both therapies. After a median follow-up of 40 months, patients receiving the combined treatment achieved the best results, and those treated with chemotherapy alone achieved the worst, the difference being particularly evident in postmenopausal women. However, while the concurrent use of chemotherapy and tamoxifen did improve the results achieved by chemotherapy alone, particularly in postmenopausal women and in those with four or more involved nodes, it did not significantly improve the results achieved by tamoxifen alone, particularly in patients with higher ER tumor concentrations. Side effects were more numerous and more severe in patients receiving chemotherapy (with or without tamoxifen). Our findings, although still preliminary, confirm that tamoxifen should be the treatment of choice for postmenopausal breast cancer patients with node-positive, ER-positive tumors. In addition, the findings suggest that tamoxifen may represent a safe alternative to chemotherapy (at least to the cytotoxic regimen we used) for younger women, provided they have ER-positive tumors. In patients with ER-positive tumors, the addition of chemotherapy to tamoxifen does not seem to improve significantly the effectiveness of tamoxifen alone.

Prospective randomised trial comparing fluorouracil versus doxifluridine for the treatment of advanced colorectal cancer.

Doxifluridine (dFUR) is a fluoropyrimidine derivative that has shown activity on a variety of solid tumours. The purpose of this study was to compare its therapeutic effect with a standard fluorouracil (FU) regimen in patients with locally advanced or metastatic colorectal cancer. 222 previously untreated patients were randomised to receive dFUR (4000 mg/m2) or FU (500 mg/m2) daily for 5 days every 28 days. The primary tumour originated in the colon in two-thirds of the cases in both groups; approximately 90% of patients had metastatic extension, and liver involvement was present in 69% of the patients in the dFUR and FU groups. A good performance status (ECOG 0-1) was recorded in 90% of cases in both arms. A median of five cycles was administered to the patients (range 1-12). Only one partial response among 110 patients in the FU arm and one complete response and five partial responses out of 112 evaluable patients in the dFUR group were observed. Time to progression was significantly longer in the dFUR group (P = 0.02); overall survival, while longer in the dFUR arm (48 weeks vs. 39 weeks), was not significantly so (P = 0.08). Toxicity was acceptable in both arms, although grade 3-4 neurological side-effects and leukopenia were more common after dFUR infusion. Despite the low response rate, our results indicate that dFUR may be a superior alternative to FU. The possibility of enhancing significantly the activity of dFUR with biochemical modulators should be further investigated.

Recovery of response to adriamycin and cyclophosphamide by lonidamine in previously treated metastatic breast-cancer patients.

Thirty-one patients with metastatic breast cancer not responding or progressing after initial response to adriamycin + cyclophosphamide (AC) treatment entered a phase 11 study with oral lonidamine in association to AC. Objective clinical responses were observed in 10 patients (32%) and consisted of 1 complete + 9 partial remissions. Disease stability and progression were observed in 8 and 13 cases, respectively. These results were obtained with a marginal toxicity in addition to that already reported for AC therapy, the main additional side effect being myalgia, which was easily manageable in most cases.

Methylxanthine, alcohol-free diet and fibrocystic breast disease: a factorial clinical trial.

A controlled clinical trial was conducted in Milan, Italy to analyze the effects of methylxanthine (MTX) and alcohol abstention on signs and symptoms of fibrocystic breast disease. A total of 192 women with a clinical and thermographic diagnosis of fibrocystic breast disease were randomly assigned to four groups on the basis of two-by-two factorial design: (1) abstention from MTX-containing beverages, (2) abstention from alcohol, (3) abstention from MTX and alcohol, and (4) no dietary advice. Of these, 162 (84.4%) were followed up at approximately 6 months. No statistically or clinically significant effect of a MTX- or alcohol-free diet was observed on signs and symptoms of fibrocystic breast disease. On the basis of the results of the present and previous randomized controlled studies, it thus appears possible to exclude that abstention from coffee and other MTX-containing beverages can substantially reduce signs and symptoms of fibrocystic breast disease within a few months.

Hodgkin's Disease in 50 Intravenous Drug Users with HIV-Infection.

Fifty cases of Hodgkin's disease in intravenous drug users (IVDU) have been collected by the Italian Cooperative Group on AIDS-Related Tumors (G.I.C.A.T.). Ninety-two per cent of the patients were males; the median age was 26 years. Persistent generalized lymphadenopathy (PGL) at onset was present in 54% of patients, AIDS in 9%, ARC in 9% while 28% were simply HIV-positive. The initial median absolute number of CD4 lymphocytes was 264/mmc. Opportunistic infections were diagnosed in 20% of patients. In most patients the histological pattern was that of mixed cellularity and lymphocytic depletion (76%). In almost half the initial symptom was a persistent lymph node enlargement due to PGL. In the majority of patients (58%) only a clinical staging and bone marrow biopsy could be performed due to the presence of opportunistic infections, rapid disease progression or refusal of pathologic staging procedures. One patient presented with a Waldeyer's ring involvement, but no other unusual presentations were observed. After MOPP alternated or followed by ABVD or MOPP alone, 15/29 CR (52%) and 14/29 PR (48%) were observed. The median duration of CR was 14 months, while the median survival of CR has not been reached; the median survival of patients treated with chemotherapy with CD4 values at presentation {geq}400/mmc was significantly superior to that in those with CD4 < 400/mmc. The overall median survival was 16 months. Twenty-eight per cent of patients receiving chemotherapy + radiotherapy developed opportunistic as well as non-opportunistic infections (21%). Lethal hepatic toxicity was observed in 2 patients. In conclusion, Hodgkin's disease in IVDU was not found to be associated with unusual presentations, as previously reported for homosexuals. Complete remissions could be achieved in over 50% of patients, but in IVDU non-opportunistic infections in addition to opportunistic infections may also limit treatment administration. The presence of parenchymal functional impairment due to drug abuse, or drug abuse-related infections, such as pneumonia, endocarditis and hepatitis, should lead to the choice of antitumour agents with no or only minor potential liver, lung and cardiac toxicity.

Cis/carboplatin + vinorelbine +/- radiotherapy in stage III and IV non small cell lung carcinoma.

The aim of this study was the retrospective evaluation of the effectiveness of cis/carboplatin + vinorelbine +/- radiotherapy in 118 patients with advanced non small cell lung carcinoma (NSCLC). To evaluate the response, pts were divided into three groups: a) Stage III pts. who received both chemotherapy and radiotherapy treatment (RC + RP = 43.75%, median survival 16.25 months); b) Stage III pts. who underwent only CT because RT was contraindicated (RC + RP = 21.95%, median survival 12.7 months); c) Stage II pts treated with CT alone (RC + RP = 20%, median survival = 12.1 months). Toxicity was mild. The results of the present study, both in terms of response rate and survival, confirm the effectiveness of the combination cis/carboplatin + vinorelbine +/- radiotherapy as palliative treatment of advanced NSCLC.

Long-term toxicity in adjuvant treatment with tamoxifen.

Long-term treatment with tamoxifen has produced few side effects, which are generally mild. Of the serious ones, all of them except eye toxicity seem to be related to the molecule's intrinsic mildly estrogen-like action, such as, for example, endometrial carcinoma. This property is also responsible for some favorable clinical effects including a lower risk of osteoporosis and cardiovascular disease. Whether tamoxifen causes neoplastic growth in patients who develop resistance to this drug is still controversial. Further prospective clinical studies are therefore needed to investigate such problems and also to evaluate less frequent side effects. Moreover, decisions on the overall duration of hormone therapy should be based on possible side effects as well as on therapeutic response.

Cyclophosphamide, methotrexate, 5-fluorouracil (CMF) in advanced gastrointestinal cancer.

The effectiveness of the cyclophosphamide + methotrexate + 5-fluorouracil schedule (CMF) in 28 patients with advanced gastrointestinal cancer has been studied. No complete remission was obtained; partial remission and objective improvement constituted 56%. The median response period is calculated at a minimum of 12 months, without significant differences between the group of patients previously subjected to palliative canalization surgery and the group of patients not subjected to this operation. The overall median survival time is 10.8 months. On the basis of the data given, the authors conclude by stressing that the CMF combination should be studied more fully in relation to its use in gastrointestinal forms of cancer.

Serum copper and ceruloplasmin levels in patients with neoplasias localized in the stomach, large intestine or lung.

Serum copper and ceruloplasmin levels were determined in patients with solid neoplasias in different sites (stomach, large intestine, lung). Statistical analysis showed that serum copper levels increased significantly in all the forms studied. The serum ceruloplasmin level, on the contrary, was high in gastric and pulmonary cancer, while in tumors localised in the large intestine the increase was not significant. In 58 cases, there was a correlation between copper and ceruloplasmin levels in the same subject; this correlation proved significant solely in gastric forms. Moreover, statistical analysis of the two parameters in question did not reveal any significant differences between localized and metastasized in forms.

Combination of mitomycin C + etoposide in advanced gastric carcinoma.

In June 1981 the authors activated a trial to evaluate the therapeutic effectiveness of the combination mitomycin C (MMC) + etoposide (VP 16) in previously untreated gastric carcinoma with measurable neoplastic lesions. Drugs were administered according to the following schedule: MMC, 12 mg/m2 i.v. day 1, + VP 16, 150-200 mg/m2 orally days 2, 3, 4, 22, 23, 24 every 6 weeks. The response rate (CR+PR) was 16.7%, which is not higher than that obtained when MMC and VP 16 are used as single agents. Overall median survival (8 months) was similar to that reported in the recent literature with combination chemotherapy.

Concurrent carboplatin (CBDCA), vindesine (VDS) and radiotherapy in stage III non small cell lung cancer (NSCLC).

AIMS: Aim of the study was to test, in a cooperative and prospective trial, the effectiveness and feasibility of a chemoradio-therapy program in stage III non small cell lung cancer (NSCLC). METHODS: The schedule consisted in carboplatin (CBDCA) 150 mg/m2/iv on days 1, 3, 5 and vindesine VDS 2.5 mg/m2/iv on days 1, 8, 15, 22 every 4 weeks for 2 cycles followed by radiotherapy 60 Gy with CBDCA 50 mg/m2 weekly as radioenhancer. The same schedule was proposed as neoadjuvant treatment in 10/47 patients (stage III A) and as exclusive treatment in 37/47 (stage III B) admitted patients. RESULTS: In the neoadjuvant subgroup partial remission was obtained in 5/10 patients, and 3 of them underwent surgery with consequent CR. In the stage III B subgroup, 2 complete remissions were obtained (survival 14 and 9+ months). Toxicity was mild. CONCLUSIONS: Our results confirm the feasibility of the schedule in stage III NSCLC.

Lithium carbonate in the treatment of drug-induced leukopenia in patients with solid tumors.

The authors report on the first part of an ongoing controlled trial (52 cases) on the evaluation of the effectiveness of Li2CO3 treatment of drug-induced leukopenia in patients with solid tumors. The results indicate that treatment with 750 mg/day per os of Li2CO3 for 7 days is capable of raising the leukocyte count to a highly significant extent, without serious side effects. The leukocytosis is due to an increase in neutrophil granulocytes.

Pulmonary asbestosis associated to pleural non-Hodgkin lymphoma.

We describe herein a case report of a patient affected by pulmonary asbestosis who developed a non-Hodgkin lymphoma originating in the pleura. The case is unusual for the uncommon site and because the chronic antigenic stimulation by asbestos bodies may have locally promoted an immunologic derangement.

Alkaline phosphatase and gamma glutamyltranspeptidase in human lymphomas.

Alkaline phosphatase (AP) and gamma glutamyltranspeptidase (GGT) were studied in normal lymphoid cells and in 28 cases of human lymphomas (23 of non-Hodgkin's and 5 of Hodgkin's disease). The expression of AP was enhanced in several samples with a high proportion of mature B cells, particularly in centroblastic-centrocytic lymphoma, whereas tissues mainly composed of T cells always showed low levels of this enzyme. GGT levels were high in thymus, as well as in centroblastic-centrocytic lymphoma and other NHL, thus demonstrating no restriction to a particular cell lineage. Some B-cell neoplasms with cellular origin different from that of centroblastic-centrocytic lymphoma, such as chronic lymphocytic leukemia and centrocytic lymphoma, had low levels of both enzymes. The role of investigation with specific antibodies against these two enzymatic activities in the physiology of lymphoma cell membrane is discussed.

Variations in serum copper and ceruloplasmin levels in advanced gastrointestinal cancer treated with polychemotherapy.

Serum copper and ceruloplasmin levels (SCL, SCeL) in 57 patients with advanced cancer of the stomach (35 cases) or large intestine (22 cases) treated with polychemotherapy were studies. In gastroenteric cancer, SCL, which are already high in untreated patients, have a tendency to increase further in cases of progression of the disease, while they seem to significantly decrease in cases of remission. SCeL during the trial appeared to be correlated to the clinical evolution of the disease only in the case of stomach cancer. In large intestine cancer, SCeL did not show any significant variation in relation to the normal range. These observations, in particular on the behavior of SCL in the neoplasms of the digestive tract, are in accordance with the results of other studies. The authors are inclined to attach a diagnostic and prognostic value to the variation in SCL and SCeL in gastrointestinal cancer.

[Experimental study on the use of cisplatin in oncology]. / Contributo sperimentale sull'impiego del Cisplatino in oncologia.

29 patients affected by ovarian (9 cases), head and neck, and miscellaneous neoplasms were treated with Cisplatinum. Most cases had been previously treated with different drugs. Complete and partial remission achieved significative results in 4, 7 and 9 ovarian patients. In the patients with head and neck tumor no complete remission and 4 partial remissions were obtained. These observations confirm that Cisplatinum may be a useful drug in chemotherapy of cancer.

[Ulcero-necrotic and lymphoproliferative naso-paranasal lesions in cocaine abuse]. / Lesioni ulceronecrotiche e linfoproliferative naso-paranasali da abuso di cocaina.

In this work are reported two clinical cases of cocaine abusers with destructive lesions of nasal-paranasal cavities. The clinical presentation and the absence of a positive history of drug addiction led to a differential diagnosis between lymphoma, idiopathic median line granuloma and Wegener granulomatosis. Biochemical and serological examinations did not prove conclusive. The diagnosis was finally formulated on the basis of the documented presence of cocaine in the biological fluids. Emphasis is placed in the difficulty of obtaining a reliable case history in this type of patients. Moreover, the Authors point out that it is advisable to test for drugs in the biological fluids prior to undertaking time-consuming diagnostic procedures for pathologies which are extremely rare in the West countries.

[Guidelines for the health protection and safety of workers exposed to antineoplastic drugs]. / Linee guida per la tutela della salute e per la sicurezza dei lavoratori esposti a chemioterapici antiblastici.

The guidelines must guarantee that occupational exposure to antineoplastic chemotherapeutic drugs is kept at the lowest level possible. Occupational exposure to these drugs can involve different categories of workers and different job tasks, such as stocking, preparation, administration, disposal, maintenance of safety cabinets and room cleaning where these activities are performed. Preventive measures should include the institution of "Centralized Units for handling antineoplastic chemotherapeutic drugs", where only specifically trained personnel are employed. Cleaning and decontamination procedures must be easily feasible and specific safety cabinets should be used in the rooms. Personnel must use adequate protective equipment and follow standardized working procedures. Information programs for the personnel should be carried out covering occupational risks, safe preventive measures and the explanation of environmental and biological monitoring.