Endocrine therapy of breast cancer. The experience of the Italian Cooperative Group for Chemohormonal Therapy of Early Breast Cancer (GROCTA).
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Biomedical subjects
Publications and source records attributed to A Farris.
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In the hope of increasing the incidence of objective remissions and the survival time of patients with small cell lung cancer, we conducted a randomized study designed to compare a treatment scheme of alternating chemotherapy featuring cisplatin+etoposide followed by cyclophosphamide+epirubicin versus conventional chemotherapy with cyclophosphamide+epirubicin+vincristine, in a total of 113 patients (56 treated with the alternating regime and 57 treated conventionally). Patients receiving the alternating drug regimen showed some increase in objective remission rates, and above all increased mean survival time (297 days versus 232). The higher incidence of side effects encountered was effectively controlled by the usual medical therapy.
504 evaluable node positive oestrogen receptor (ER) positive breast cancer patients were randomly allocated to receive either 5 years tamoxifen treatment or chemotherapy [six courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 4 courses of epirubicin] or a combination of both treatments. At a median follow-up of 5 years tamoxifen appeared to be more effective than chemotherapy, the difference being highly significant in postmenopausal women. The addition of chemotherapy to tamoxifen was not able to significantly improve the results achieved by tamoxifen alone, irrespective of menopausal status. Trends were similar even after stratification for the number of involved nodes. The protective effect of tamoxifen in terms of reduction of the odds of death increased with time and no rebound phenomena on recurrence or death has occurred so far after the completion of tamoxifen treatment. Overall, the prognostic value of number of involved nodes and of progesterone receptor (PgR) status was confirmed by multivariate analysis. However, the predictive value of PgR was lost in patients receiving tamoxifen alone. Similarly, the degree of ER positivity was not predictive of the response to tamoxifen. Tamoxifen treatment should still be regarded as the gold standard for postmenopausal ER positive patients. In younger women the antioestrogen proved to be safe and at least as effective as chemotherapy. However, the analysis of the annual risks suggests that the concurrent or the sequential use of chemotherapy and tamoxifen might represent a more appropriate treatment for this patient subset, particularly for those with four or more involved nodes. Different cut-offs of ER and PgR assays from those we have arbitrarily employed in the present analysis should probably be used to select more properly the patients who can benefit from endocrine therapy.
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A 43-year-old homosexual man with the Acquired Immunodeficiency Syndrome (AIDS) developed cutaneous molluscum contagiosum-like lesions on face, ears, neck, hands and feet. He was admitted to our unit with fever, malaise and headache. Cytologic examination of skin brushing revealed numerous encapsulated budding yeasts, identified as Cryptococcus neoformans. Such a finding calls for a cytologic examination of skin lesions in patient with AIDS who present with fever and headache, in order to rule out a potentially life-threatening fungal infection.
A 24-year old male patient developed, on both legs, lesions typical of Mibelli's porokeratosis 22 months after bone marrow transplantation, under treatment with cyclosporin A. He denied any family history. Mibelli's porokeratosis seldom develops after an immunosuppressive treatment, and to our knowledge it has exceptionally been described after bone marrow transplantation. A possible complication of Mibelli's porokeratosis is the development of Bowen's disease, basal or squamous cell carcinomas. Immunosuppressive treatment might facilitate the degeneration. For this reason, these subjects should be periodically and carefully examined.
Forty-one patients affected by solid tumors of the head and neck were treated with neoadjuvant therapy before radiotherapy or surgery. All patients received therapy with cisplatinum 100 mg/m2 day 1 and 5-fluorouracil 1000 mg/day for days 1-5 by continuous infusion with a portable chronoinfusor. After three cycles, we observed an objective response in 34/41 patients (82.9%), with 9 (21.9%) complete remissions and 25 (61%) partial remissions. The main side effects were few and controllable. In our experience, neoadjuvant chemotherapy was able to induce a significant remission in 4/5 of patients, with better prospects for subsequent surgery and/or radiotherapy.
The aim of the present study is to confirm the antitumor activity of orally administered idarubicin (IDA) in patients with advanced breast cancer. Doxorubicin (ADRIA) was chosen as control treatment and the patients were randomized to receive either IDA or ADRIA according to a 2:1 ratio. Sixty-three patients, 77% of whom were pretreated with chemotherapy excluding anthracyclines, entered the study. The doses were: IDA 45 mg/m2 orally on 3 consecutive days every 28 days: ADRIA 75 (60) mg/m2 intravenously every 21 days. A complete + partial response (CR + PR) was observed in 11/37 (30%) evaluable cases treated with IDA and in 6/19 (32%) cases treated with ADRIA. If all the patients were included, the CR + PR remission rates were 27.5 and 27%, respectively. There were no significant differences as regards time to remission, duration of remission and survival. None of 10 cases who crossed over the treatments responded to the second therapy. The most frequent side effects of IDA were myelosuppression and nausea/vomiting. The only significant statistical difference between the two anthracyclines was the lower incidence of alopecia after IDA. Although there were 3 cases of cardiotoxicity after ADRIA, 2 of which severe, no case of clinical cardiotoxicity was observed after IDA. The present study confirms that orally administered IDA is an active agent in advanced breast cancer.
A group of 55 patients with advanced non-small cell bronchogenic carcinoma entered a random study on combined cisplatin (CDDP) and etoposide (VP16), either intermittently (I = CDDP 60 mg/m2 day 1 and VP16 120 mg/m2 day 1-3 every 3-4 weeks) or weekly (W = CDDP 20 mg/m2 and VP16 120 mg/m2). Five out of 31 (16%) evaluable patients in group I and 6/27 (22%) in group W obtained partial remission (no statistical difference). Toxicity was mild and survival was similar for both groups. The authors conclude that the weekly combination of CDDP plus VP16 is neither less toxic nor more effective than the intermittent one.
Eighty patients with advanced gastrointestinal tumors (64% with colorectal cancer) entered a phase III prospective randomized study with 5-fluorouracil (5-FU) vs 5-FU + folinic acid (FA) The treatment included 5-FU, 600 mg/m2/week for 6 weeks, given as i.v. bolus alone (arm A), or administered by rapid injection half-way through a one-hour infusion of FA, 200 mg/m2/week for 6 weeks (arm B). Partial remission (PR) was achieved in 1 out of 30 (3%) evaluable patients for 6 months in arm A, and in 10 out of 34 (29%) patients in arm B, with a median duration of 8 months (range 6-17) (comparison of the response rate: P = 0.005). In patients with colorectal cancer the response rate was 5% and 27% in arm A and in arm B respectively (P = 0.06). Two patients, who were resistant to 5-FU alone, achieved PR after treatment with 5-FU + FA. Diarrhea was observed in 14/42 patients (33%) in arm B (grade 1-2 in 10 and grade 3 in 4) and in 2/38 patients (5%) in arm A (P = 0.005). Other side effects such as nausea/vomiting, myelosuppression and stomatitis were infrequent and of mild intensity in both arms. No statistical difference in survival was detected when comparing the two groups (estimated median survival 8 months and 11 months for arm A and arm B respectively). These results seem to indicate that the weekly regimen of 5-FU + FA has a superior response rate compared to 5-FU alone, and that it is well tolerated. However, the advantage is not reflected in overall survival.
A study of the relative 2dG6P utilization in mononuclear cells from a group of 150 women with breast cancer was undertaken to evaluate a possible negative correlation between G6PD deficiency and cancer, as suggested by some authors. Twenty-one women (14.00%) were heterozygotes and 2 were homozygotes (1.33%). The prevalence found was not different from that expected. It would therefore seem that the G6PD Mediterranean allele does not play a protective role against the development of breast cancer.
From February 1983 to January 1985, 497 patients with advanced breast cancer were randomly allocated to receive either epirubicin or doxorubicin in the following combination chemotherapy regimen: fluorouracil (5-FU) 500 mg/m2 intravenous (IV) on days 1 and 8; epirubicin or doxorubicin 50 mg/m2 IV on day 1; cyclophosphamide 500 mg/m2 IV on day 1 (FEC or FAC). Cycles were repeated every 21 days until progression or to cumulative doses of 700 mg/m2 for epirubicin and 550 mg/m2 for doxorubicin. Dose reductions were applied according to the standard criteria. Activity was evaluated in 443 patients (222 in the FEC arm and 221 in the FAC arm). The two experimental groups were comparable in age, performance status, menopausal status, histology, previous treatments, and site of the disease. The overall response rate (complete response and partial response [CR + PR]) was not significantly different: 53.6% for FEC and 56.5% for FAC. The median time to progression was 273 days for FEC and 314 days for FAC; the median survival time was 591 and 613 days, respectively. Leukopenia, anemia, nausea, and vomiting were significantly lower in patients treated with FEC. As for cardiotoxicity, four cases of congestive heart failure (CHF) were recorded among patients treated with FAC while only one was observed in the FEC group. These results indicate that epirubicin in a combination chemotherapy regimen is as active as doxorubicin and is significantly less toxic.
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The present paper reports a case of osteo-onychodysplasia (nail-patella syndrome). There are very few descriptions of this syndrome in the orthopaedic literature, possibly because it is rare for the morphological changes in the knee and the associated abnormalities to require or be amenable to treatment. In the present case an accidental sprain of the right knee caused recurrent dislocation of the patella that necessitated surgical intervention.
The authors describe their experience with colorectal cancer screening by means of the Hemoccult test for the detection of occult fecal blood according to Gregor's method. In particular, the decentralized aspect of the screening is examined, and the results discussed are in agreement with those observed in larger study populations. The authors go on to stress the effective possibility of conducting this type of screening also on the basis of collaboration with general practitioners.
Serum tissue polypeptide antigen (TPA) was measured by RIA in 151 female patients who had had mastectomies for breast cancer, in 30 patients with benign breast disease, and in 30 normal controls. The marker was elevated in 52 neoplastic patients (25 with metastases) and in six cases of benign breast disease. At the time of our observation 15 cancer patients were at stage I, 53 at stage II, 48 at stage III, and 35 at stage IV, the prevalence of high TPA values significantly correlated with staging gradually increasing from 0 to 71.4% from stage I to IV. In patients with breast cancer TPA was significantly higher in the subgroup with metastatic disease compared to patients with apparently inactive disease. Nineteen patients without (group A) and 35 with metastases (group B) were monitored with serial measurements of TPA for 8-24 months. Group B was receiving either hormone or chemotherapy. In 10 group A patients TPA was either higher or rose 1-7 months prior to the clinical detection of metastases. Twenty-two patients from Group B had disease progression: In 20 of them TPA rose further. The remaining 13 patients had an apparent disease regression, and in 11 instances TPA either fell or remained normal. Thus TPA can detect early recurrence of breast cancer before clinical and instrumental methods; moreover, it might prove important in evaluating tumor response to treatment and in follow-up of patients with metastatic disease. Finally, serial measurements of TPA could identify previous false-positive results, thus improving the specificity of the test.
High dose MAP (medroxyprogesterone acetate) and TAM (tamoxifen) were administered orally to 31 postmenopausal patients with advanced breast cancer. CR (complete remission) was achieved in 1 (3%) and PR (partial remission) in 11 (32%) patients for a median duration of 12 months. The treatment was well tolerated and in no instance was interrupted because of toxicity. This study does not support the hypothesis that the combination of MAP and TAM gives better results than the single agents.