[Adriamycin as a single agent in various forms of advanced neoplasia of adults and children (author's transl)].
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Adult↗
Biomedical subjects
G Tancini
Publications and source records attributed to G Tancini.
[Adriamycin in combination and in combined treatment modalities (author's transl)].
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Alopecia↗
Adriamycin plus cyclophosphamide in advanced bronchial carcinoma.
Adriamycin (40 mg/m2 i.v., on day 1) plus cyclophosphamide (200 mg/m2 orally, day 1 to 5) were given to 23 patients with advanced lung cancer. Administration cycles were repeated every 3 weeks. No patient had been previously treated with chemotherapy, 5 received prior radiotherapy. Objective improvement was observed in 7 patients, partial remission was observed in 3. The median duration of response was 2 months.
Adult↗
Second-line therapy with interferon-alpha plus vinblastine in metastatic renal cell cancer patients progressed under interleukin-2 subcutaneous immunotherapy.
AIMS AND BACKGROUND: Interferon (IFN) +/- vinblastine (VNB) has appeared to be effective as first-line therapy of metastatic renal cell cancer. This study was performed to establish the efficacy of IFN plus VNB in metastatic RCC previously treated with interleukin-2 (IL-2). METHODS: The study included 14 metastatic renal cell cancer patients who did not respond to IL-2 subcutaneous therapy or who relapsed after initial response or stable disease. IFN-alpha 2a was given subcutaneously at 3 million U thrice a week in association with VNB (0.1 mg/kg i.v. every 21 days) until progression or toxicity. Patients were considered as evaluable when they were treated for at least 1 month. RESULTS: Evaluable patients were 13/14. No patient had a complete response. Partial response was achieved in 2/13 (15%) patients. Stable disease was seen in 5/13 patients, and the last 6 progressed. CONCLUSIONS: This study, by showing a tumor response rate comparable to that reported with first-line therapy, suggests that previous IL-2 immunotherapy does not influence negatively the efficacy of IFN+VNB in metastatic renal cell cancer.
Aged↗
Clinical efficacy of cancer subcutaneous immunotherapy with interleukin-2 in relation to the pretreatment levels of tumor growth factor insulin-like growth factor-1.
AIMS AND BACKGROUND: IGF-1 has been proven to be one of the most important growth factors for normal and neoplastic cells. Abnormally high levels of IGF-1 have been observed in cancer patients. Since it has been demonstrated that some growth factors may counteract the action of antitumor cytokines, the presence of increased IGF-1 concentrations could reduce the efficacy of cancer biotherapies with cytokines, such as IL-2. The present study was performed to evaluate the efficacy of IL-2 immunotherapy in relation to the pretreatment levels of IGF-1 in advanced cancer patients. METHODS: The study included 20 consecutive patients with metastatic renal cell cancer who were treated subcutaneously with IL-2 at 6 million IU/day for 5 days/week for 6 weeks. IGF-1 serum levels were measured by RIA on venous blood samples collected before the immunotherapy, after 3 weeks, and at the end of IL-2 injection. RESULTS: Objective tumor regressions were obtained in 5/20 patients, consisting of 1 complete response (CR) and 4 partial responses (PR). Nine patients had stable disease and the last 6 patients progressed. Abnormally high pretreatment levels of IGF-1 were seen in 13/20 patients. The percent of clinical responses (CR + PR) was significantly higher in patients with normal pretreatment concentrations of IGF-1 than in those with elevated levels (4/7 vs 1/13, P < 0.01). No significant changes in mean IGF-1 levels occurred during IL-2 therapy. However, mean IGF-1 levels increased in progressing patients and decreased in those with a response or stable disease, even though none of the differences was statistically significant. CONCLUSIONS: The study showed that high pretreatment levels of IGF-1 are associated with a reduced efficacy of IL-2 immunotherapy of renal cancer. Further studies are required to establish whether IGF-1 levels simply reflect the extension of disease, or whether they may influence per se the action of IL-2.
Analysis of Variance↗
Endocrine effects of granulocyte colony-stimulating factor in cancer patients.
AIMS AND BACKGROUND: In addition to well-documented endocrine properties of interleukins, hemopoietic growth factors could also exert hormonal activities. In fact, our previous studies have shown that GM-CSF may stimulate cortisol and GH release. In contrast, few data only are available about the possible effects of G-CSF. This study was carried out to investigate endocrine effects of G-CSF in cancer patients. METHODS: The study included 8 cancer patients who were investigated after G-CSF (0.3 mg subcutaneously) or during saline infusion alone as control by collecting venous samples at zero time and after 2, 4, 6 and 8 h. Serum levels of cortisol, GH, PRL, FSH. LH, TSH and melatonin were measured by the RIA method. RESULTS: The circadian rhythm of cortisol was not influenced by G-CSF. No significant differences in mean levels of GH, PRL, FSH or LH were seen after G-CSF and during saline infusion. Both TSH and melatonin decreased after G-CSF, without, however, significant differences with respect to the values seen on saline alone. CONCLUSIONS: The study showed that G-CSF has no substantial endocrine affects in humans. Therefore, G-CSF would differ from GM-CSF not only for its hemopoietic properties, but also from an endocrine point of view.
Granulocyte Colony-Stimulating Factor↗
Effects of one-year adjuvant treatment with tamoxifen on bone mineral density in postmenopausal breast cancer women.
In this study, the authors have analyzed the possible effects of one-year adjuvant treatment with tamoxifen on bone mineral density in postmenopausal breast cancer women. Bone mineral content was studied by photon absorptiometry (I-125), whereas bone balance was analyzed indirectly by serum PTH, osteocalcin, calcitonin, calcium and alkaline phosphatase levels. Bone mineral content and serum bone-related substances were measured before starting treatment and after one year. Results were analyzed using Student's t test for paired data. No difference was found between the two measurements for bone mineral content, PTH, calcitonin, calcium and alkaline phosphatase levels. Measurements at entry and after one year of treatment showed a statistically significant difference (P<0.001) only for osteocalcin. In accordance with other authors, we can conclude that treatment with tamoxifen does not cause an increase in menopausal bone resorption. The finding that osteocalcin levels decreased after one year of therapy with tamoxifen is interesting, but further studies are necessary to clarify the role of such levels in predicting a turnover of bone balance towards osteoblastic activity.
Adult↗
Characterization of cancer-related disseminated intravascular coagulation in relation to tumor necrosis factor-alpha blood concentrations: possible therapeutic role of pentoxifylline.
AIMS AND BACKGROUND: Preliminary experimental data suggest the involvement of tumor necrosis factor (TNF) in determining endothelial damage related to disseminated intravascular coagulation (DIC). The present study was performed to investigate TNF secretion in DIC occurring in metastatic solid tumor patients and to evaluate the possible therapeutic role of pentoxifylline, which has been proven to have a TNF-lowering activity. METHODS: The study included 20 metastatic solid tumor patients who showed clinical and laboratory signs of DIC. Pentoxifylline was given orally at a dose of 1200 mg/day for 28 days. RESULTS: Abnormally high levels of TNF were found in 13/20 patients, and mean TNF serum levels observed in patients were significantly higher than those seen in a control group of 50 healthy subjects. Fibrinogen plasma concentrations were low in 11 cases. Patients with low fibrinogen values showed significantly higher mean TNF levels than those with normal or elevated concentrations. Pentoxifylline therapy induced a significant decrease in mean TNF concentrations and a significant increase in mean platelet number, which returned to within the normal range in 11/20 patients. An increase in platelets in response to pentoxifylline was more evident in patients with elevated pretreatment TNF values. CONCLUSIONS: Our results suggest the existence of abnormally high blood levels of TNF in cancer-related DIC, mainly in the presence of low fibrinogen values. Moreover, they indicate that pentoxifylline therapy may determine a decrease in TNF levels in DIC patients, an event associated with an increase in platelet number.
Adult↗
Clinical efficacy of the aromatase inhibitor anastrozole in relation to prolactin secretion in heavily pretreated metastatic breast cancer.
AIMS AND BACKGROUND: It is known that the aromatase inhibitors may act by decreasing estrogen levels. Moreover, it is known that estrogens may stimulate the release of prolactin (PRL), which is a growth factor for breast cancer. This phase II study was performed to evaluate the effects of the novel aromatase inhibitor anastrozole on PRL secretion in metastatic breast cancer and the possible influence of PRL pretreatment levels on the efficacy of therapy. METHODS: The study involved 14 pretreated metastatic breast cancer patients with a poor clinical status. Anastrozole was given orally once a day at 1 mg/day for at least 2 months. To evaluate PRL secretion, venous blood samples were collected before treatment and at 1-monthly intervals during treatment. RESULTS: The clinical response consisted of partial response (PR) in 2, stable disease (SD) in 5 and progressive disease (PD) in the remaining 7 patients. Abnormally high pretreatment levels of PRL were seen in 5/14 (36%) patients. Progressing patients showed significantly higher pretreatment levels of PRL than those who achieved PR or SD. None of the patients with high PRL pretreatment levels showed a decline in PRL levels on treatment with anastrozole. CONCLUSIONS: This preliminary study suggests that anastrozole has no inhibitory effect on PRL secretion in metastatic breast cancer and that the evidence of abnormally elevated concentrations of PRL prior to therapy is generally associated with a lack of efficacy.
Administration, Oral↗
Neoadjuvant chemotherapy to radiation and concurrent chemoradiation for locally advanced squamous cell carcinoma of the cervix: a review of the recent literature.
Radiotherapy is the standard treatment for locally advanced cervical cancer; nevertheless it fails to control disease progression within the irradiation fields in more than 40% of cases, particularly in patients with bulky tumor. Distant metastases are not infrequent in more advanced cases. Chemotherapy has been integrated with radiotherapy to improve local control and treat distant subclinical metastases. Schedules of combined treatment more frequently represented by neoadjuvant chemotherapy followed by radiation (NACT) and by concomitant chemotherapy and radiation (CT-RT). A review of the recent literature is presented. The role of NACT is controversial: high response rates are reported but doubtful advantages in terms of survival or local control have been shown. In randomized trials, hydroxyurea concomitant to radiation improves local control and survival, particularly in stage IIIB and IVA. Several randomized trials of concurrent chemoradiation with 5FU, cisplatin and mitomycin C are underway, but few have been published: no significative differences are reported in term of local control or survival. Acute toxicity is higher than in radiation alone, but usually manageable. For the analysis of late morbidity a longer follow-up is required. Large randomized trials of adequate radiotherapy versus concomitant chemoradiation are necessary to refine our understanding of the benefits of this integrated treatment.
Antineoplastic Combined Chemotherapy Protocols↗
Endocrinological study of the dopaminergic regulation of prolactin release in metastatic breast cancer.
AIMS AND BACKGROUND: Prolactin (PRL) may be a growth factor for breast cancer. Abnormally high levels of PRL have been proven to be associated with a poor prognosis in metastatic breast cancer. However, most studies have been limited to the evaluation of basal levels of PRL rather than its response to the classical endocrine dynamic tests. This study was performed to analyse the dynamic secretion of PRL under stimulatory and inhibitory tests in metastatic breast cancer. METHODS: The study included 10 untreated metastatic breast cancer women, who were evaluated after the classical stimulatory and inhibitory tests for PRL secretion with the antidopaminergic agent Metoclopramide (10 mg iv as a bolus) and with L-dopa, respectively. Serum levels of PRL were measured by RIA before and at subsequent intervals after drug administration. PRL levels were considered to be elevated when they were higher than 25 ng/ml. RESULTS: Abnormally high basal levels of PRL were seen in 6/10 patients. L-dopa was unable to inhibit PRL secretion, whose mean concentrations paradoxically significantly increased in response to L-dopa, with values comparable to those observed after the classical stimulatory test with metoclopramide. CONCLUSIONS: This study confirm the existence of hyperprolactinemia associated with metastatic breast cancer. In addition, by showing a paradoxical rise of PRL in response to L-dopa, which inhibits PRL secretion in physiological conditions, this study would suggest that breast cancer-related hyperprolactinemia may depend at least in part on endogenous disease-related neuroendocrine alterations.
Adult↗
Chemotherapy and angiogenesis in advanced cancer: vascular endothelial growth factor (VEGF) decline as predictor of disease control during taxol therapy in metastatic breast cancer.
Angiogenesis is essential for tumor growth. Since vascular endothelial growth factor (VEGF) represents the main angiogenic factor, the control of VEGF secretion could constitute the most important mechanism to achieve the inhibition of angiogenesis-related processes. High blood concentrations have been proven to correlate with poor prognosis in advanced cancer. In experimental conditions, chemotherapeutic agents such as taxol appeared to inhibit VEGF-induced angiogenesis, while at present there are no data about the influence of chemotherapy on VEGF secretion in cancer patients. This preliminary study was performed to evaluate the effect of taxol therapy on VEGF secretion in advanced cancer patients in relation to the clinical response. The study included 14 patients with metastatic breast cancer who were treated with taxol monochemotherapy (175 mg/m2 i.v. every 21 days for three cycles). Serum levels of VEGF were measured by ELISA in blood samples collected before therapy and at 21-day intervals. The clinical response consisted of partial response (PR) in three and stable disease (SD) in six patients, whereas the other five patients had progressive disease (PD). Abnormally high pre-treatment levels of VEGF were seen in 8/14 patients. VEGF mean values significantly decreased during taxol therapy in patients with PR or SD, whereas no decline was observed in patients with PD. Moreover, the percent of normalization or decline greater than 50% in VEGF levels was significantly higher in patients with PR or SD than in those with PD (5/9 vs. 0/5). This preliminary study would suggest that the efficacy of taxol therapy in metastatic breast cancer - at least in terms of disease stabilization - may be associated with a decrease in VEGF blood levels followed by potential inhibition of cancer-related neovascularization.
Aged↗
Neuroimmunomodulation in cancer patients: correlations between melatonin and beta-endorphin blood levels and T helper/suppressor ratio.
The pineal gland and opioid peptides play roles in the neuroendocrine control of immunity. Both neuroendocrine and immune dysfunctions have been observed in cancer but the importance of the altered secretion of neurohormones in the immunoincompetence of cancer patients has never been investigated. This study concomitantly evaluated neuroendocrine and immune functions in 40 patients with early or advanced neoplastic disease. In each patient, melatonin and beta-endorphin blood levels and lymphocyte subtypes were determined on venous blood samples collected during the morning. Metastatic patients had lower melatonin levels and a lower T4/T8 ratio than patients without metastases but no significant correlation was found between melatonin and the T4/T8 ratio. beta-endorphin levels appeared to be normal in all patients. These results suggest that melatonin and beta-endorphin secretion have no role in determining immune dysfunctions in cancer.
Adult↗
Serum levels of melatonin in cancer patients and their relation to body sizes.
Melatonin secretion is often enhanced in patients with cancer. In the light of a reported correlation between melatonin levels and body size, we investigated blood levels of this pineal hormone in a group of 72 patients affected by cancer, 30 of whom had body weight within the normal range, 30 were obese and the last 12 cases had body weight below the normal range, in order to establish whether in fact melatonin blood concentrations were related to body size. Melatonin levels were high in 19/72 patients (26%). The mean levels of the pineal hormone were similar in patients with normal, low and high body weight. Finally, there was no significant correlation between melatonin values and body weight, height or surface. Melatonin secretion thus does not appear to be influenced by body size in cancer patients.
Body Constitution↗
Prolactin secretion in testicular cancer patients.
The role of prolactin (PRL) in testicular function and in its disorders is still obscure. To draw some preliminary conclusions on the relation between the PRL and testis cancer, we assessed the PRL response to thyrotropin-releasing hormone (THR) in 15 patients with testicular cancer (8 seminoma; 6 nonseminoma; 1 leydigioma), and in 11 healthy male subjects as controls. The results showed that 5/15 cancer patients gave no PRL response to TRH; 4 of them had a nonseminoma and the fifth a seminomatous testis carcinoma. Patients with nonseminoma had significantly lower mean peak values of PRL after TRH than controls or patients with seminoma. The biological significance of the altered PRL response to TRH in testicular carcinoma has still to be established.
Adult↗
Opioid receptors in human neoplasms: growth hormone and prolactin response to morphine, met-enkephalin and buprenorphine in cancer patients.
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Adult↗
Serum levels of soluble interleukin-2 receptors and their relation to CD4/CD8 ratio in patients with advanced solid tumors.
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Adult↗
The pineal gland and breast cancer: serum levels of melatonin in patients with mammary tumors and their relation to clinical characteristics.
Several studies have suggested that the pineal gland hormone melatonin may influence the growth of breast cancer. The importance of melatonin blood concentrations in the clinical history of human breast cancer, however, has still to be defined. To further investigate this problem, we used a RIA method to assay serum levels of the pineal hormone in 74 untreated breast cancer patients, clinical stage T1-3 NO-2 MO, and in 46 age-matched healthy women as controls. Mean serum melatonin levels were significantly higher in patients than in controls. Melatonin concentrations were highest in breast cancer patients with the best prognosis (i.e. estrogen receptor-positive/node-negative cases). Mean levels of melatonin were significantly higher in estrogen receptor-positive patients than in the negative ones. They were also higher in node-negative than in node-positive cases, and in progesterone receptor-positive patients than negative ones, but none of these differences was statistically significant. No difference was observed in relation to menopausal status and to tumor histotype. These results suggest that melatonin plays a role in the hormone-dependency of human breast cancer.
Adult↗