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Biomedical subjects

G Arcangeli

Publications and source records attributed to G Arcangeli.

At least 19 recordsLinked to original sources
PubMed2006

A double-blind, vehicle-controlled clinical study to evaluate the efficacy of MAS065D (XClair), a hyaluronic acid-based formulation, in the management of radiation-induced dermatitis.

This study was designed to assess the efficacy and tolerability of MAS065D (Xclair) compared to a vehicle control in the management of radiation dermatitis in patients receiving radiotherapy for breast cancer. Twenty patients were randomized blindly to use the two study substances, three times daily, on separate sections of irradiated skin throughout the duration of radiotherapy and for two weeks afterwards. Patients were monitored before therapy, weekly during therapy, and for 2 weeks after radiotherapy was completed. Skin appearance according to National Cancer Institute (NCI) toxicity criteria, erythema rating, transepidermal water loss (TEWL), skin hydration, patients' view of itch, pain, acceptance, and view of each cream and adverse events, were monitored; at the final visit patients and investigators expressed their preference for one of the creams. MAS065D showed statistically significant superiority in the outcomes of NCI grading for radiation dermatitis and erythema. Patients' and investigators' preferences for one of the study substances were statistically in favor of MAS065D. Very few patients recorded nonzero itch and pain scales, so no significant differences emerged between the two groups. It was concluded that MAS065D can provide an effective option for managing radiation dermatitis although further studies are needed to assess its effect on pain and itch.

Breast Neoplasms↗
PubMed2004

Angiogenesis and extracellular matrix remodelling in bronchioloalveolar carcinomas: distinctive patterns in mucinous and non-mucinous tumours.

AIM: Bronchioloalveolar carcinomas (BACs) are rare primitive lung adenocarcinomas growing along the alveolar septum without stromal, vascular or pleural invasion. We report an immunohistochemical study of their vascular microenvironment. METHODS AND RESULTS: In three mucinous BACs (M-BAC) and three non-mucinous BACs (NM-BAC) we examined the following parameters in comparison with the normal lung: (i) constituents of the alveolar extracellular matrix; (ii) qualitative and quantitative changes of alveolar capillaries; and (iii) expression of vascular endothelial growth factor (VEGF) by tumour cells. In M-BAC, the alveolar matrix was unchanged compared with the normal parenchyma. Capillaries expressed normal alveolar endothelial markers and their average surface was calculated, as in normal lung, as 8%. VEGF was negative in tumour cells. In NM-BAC, the alveolar wall was thickened by deposits of fibronectin and type III collagen containing myofibroblasts and the basement membrane was disrupted. Capillaries did not retain alveolar endothelial markers and their surface was calculated as 19%. Tumour cells expressed high levels of VEGF. CONCLUSIONS: In contrast to NM-BAC, M-BAC do not modify the alveolar structure and seem to exploit the normal alveolar vascular bed to grow, without inducing neoangiogenesis. A better understanding of the mechanisms of growth of lung cancers may have implications for future anti-angiogenic therapeutic strategies.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Effects of silica on human lung fibroblast in culture.

Silica has been reported to directly stimulate cellular proliferation of human lung fibroblasts, and silica-treated macrophage supernatants induce fibroblast proliferation and some of their biosynthetic activities. Alveolar macrophages produce increased amount of tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta). Lung fibroblasts are producers of interleukin-6 (IL-6). We investigated the capacity of lung fibroblasts obtained from normal and silicosis subjects to elaborate IL-6 in response to TNF-alpha and to TGF-beta. Our data show that TNF-alpha and TGF-beta are able to stimulate the proliferation of human lung fibroblasts in culture, to increase the collagen production of the cells and are both able to increase IL-6 production by lung fibroblasts of patients with silicosis. We hypothesise that silica is able to stimulate lung fibroblast both directly, increasing the cell proliferation, and indirectly stimulating the release of factors (as TNF-alpha and TGF-beta) from activated alveolar macrophages, that are able to increase proliferative and biosynthetic activities of fibroblast.

Cell Division↗
PubMed2001

Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis.

BACKGROUND/AIMS: Although human and experimental studies have shown that apoptosis plays a role in hepatocyte death in alcoholic liver disease, its clinical and biological significance has not been investigated in alcoholic hepatitis (AH). The aim of this study was to quantify hepatocyte apoptosis in AH and to attempt to relate it to the clinical and biological severity of the disease. METHODS: The hepatocyte apoptotic index was determined using a double in situ transferase-mediated dUTP nick end (TUNEL) and CD15 (neutrophils) labelling on 35 liver biopsies from patients with AH lesions of different severities. The specificity of TUNEL labelling for apoptosis was monitored both by morphology and fractin (a caspase actin cleavage site) immunostaining. RESULTS: The hepatocyte apoptotic index ranged from 0.3 to 28% and was related to the severity of alcoholic hepatitis as measured by the Maddrey score (P < 0.05; Mann-Whitney test) while ballooning (which reflects hepatocytes potentially undergoing necrosis) and neutrophil indexes were not. CONCLUSIONS: This suggests that hepatocyte apoptosis could be a therapeutic target to treat or to prevent alcoholic hepatitis in cirrhotic patients. Co-localization of apoptotic hepatocytes with neutrophils and the strong quantitative correlation would suggest an apoptosis dependent transmigration of neutrophils.

Actins↗
PubMed2001

Asbestos exposure assessment by mineralogical analysis of bronchoalveolar lavage fluid.

Mineralogical analysis of bronchoalveolar lavage fluid (BALF) by electron microscopy can represent the most suitable method for assessing asbestos exposure. However, it has been claimed that no standardized or systematic approach to the subject of mineralogical analysis exists. This study aimed to evaluate BALF mineralogical analysis by transmission electron microscopy as biomarker of asbestos fiber load. BALF was examined in 108 exposed workers and 57 patients who underwent diagnostic fiberoptic bronchoscopy for various clinical purposes. Asbestos bodies in BALF were counted with a phase-contrast microscope. Fibers were counted and analyzed by transmission electron microscopy, which showed a significant difference between the two populations and positive results for all exposed subjects. Only 82.2% of the exposed population tested positive for asbestos bodies. Subjects with long-term exposure had higher concentrations of fibers than did those with more recent exposure, probably because of the higher workplace exposure levels in the past. The results of the study confirm that fiber concentration in BALF can be considered as a reliable biomarker of past asbestos exposure, even many years after the end of exposure.

Adult↗
PubMed1998

Radiation therapy in the management of symptomatic bone metastases: the effect of total dose and histology on pain relief and response duration.

PURPOSE: In order to better define variables and factors that may influence the pain response to radiation, and to look for a radiation regimen that can assure the highest percentage and the longest duration of pain relief, we performed a prospective, although not randomized, study on patients with bone metastases from various primary sites. METHODS AND MATERIALS: From December 1988 to March 1994, 205 patients with a total of 255 solitary or multiple bone metastases from several primary tumors were treated in our radiotherapy center with palliative intent. Irradiation fields were treated with three main fractionation schedules: (1) Conventional fractionation: 40-46 Gy/20-23 fractions in 5-5.5 weeks; (2) Short course: 30-36 Gy/10-12 fractions in 2-2.3 weeks; (3) Fast course: 8-28 Gy/1-4 consecutive fractions. Pain intensity was self-assessed by patients using a visual analogic scale graduated from 0 (no pain) to 10 (the strongest pain one can experience). Analgesic requirement was assessed by using a five-point scale, scoring both analgesic strength and frequency (0 = no drug or occasional nonopioids; 1 = Nonopioids once daily; 2 = Nonopioids more than once daily; 3 = Mild opioids (oral codeine, pentazocine, etc.), once daily; 4 = Mild opioids more than once daily; 5 = Strong opioids (morphine, meperidine, etc.). Complete pain relief meant the achievement of a score < or = 2 in the pain scale or 0 in the analgesic requirement scale. Partial pain relief indicated a score of 3 to 4 or of 1 to 2 on the former and latter scale, respectively. RESULTS: Total pain relief (complete + partial) was observed in 195 (76%) sites, in 158 of which (62%) a complete response was obtained. Metastases from NSC lung tumors appeared to be the least responsive among all primary tumors, with 46% complete pain relief in comparison to 65% and 83% complete relief in breast (p = 0.04) and in prostate metastases (p = 0.002), respectively. A significant difference in pain relief was detected among the several ranges of total dose delivered to the painful metastases, with 81%, 65%, and 46% complete relief rates in the 40-46 Gy, 30-36 Gy (p = 0.03), and 8-28 Gy (p = 0.0001) dose ranges respectively. A straight correlation between total dose and complete pain relief was confirmed by the curve calculated by the logistic model which shows that doses of 30 Gy or more are necessary to achieve complete pain relief in 70% or more of bone metastases. This correlation holds also for the duration of pain control, as shown by the actuarial analysis of time to pain progression. Multivariate analyses, with complete pain relief and time to pain progression as endpoints show a highly significant effect of radiation dose (p = 0.0007) and performance status (p = 0.003), with lower rates of complete pain relief and shorter time to pain progression observed after smaller radiation total doses or higher Eastern Cooperative Oncology Group (ECOG) scores. CONCLUSION: Although single-dose or short course irradiation is an attractive treatment in reducing the number of multiple visits to radiotherapy departments for patients with painful bone metastases, it is nevertheless clear that aggressive protracted treatments seem to offer significant advantages especially for patients in whom the expected life span is not short.

Analgesics↗
PubMed1998

Enhancement of radiation response by paclitaxel in mice according to different treatment schedules.

PURPOSE: The aim of our study was to determine if paclitaxel could be used as a radiosensitizer in vivo. MATERIALS AND METHODS: Paclitaxel was tested as a single agent and combined with an X-ray treatment. Paclitaxel was administered i.p. in doses from 30 to 120 mg/kg b.w. to (C3D2F1) mice bearing spontaneous mammary carcinoma. Tumor growth delay (TGD) or tumor control dose (TCD50, radiation dose needed to induce local tumor control in 50% of irradiated animals) and moist desquamation dose (MDD50, radiation dose needed to induce serious moist desquamation in 50% of the non-tumor-bearing feet) were the endpoints. DNA flow cytometric analysis was performed. RESULTS: DNA analysis demonstrated a G2/M block of tumor cells and a depletion of cells in S phase, with a maximum at 24 h from paclitaxel administration. Administering paclitaxel, in graded doses, 15 min before a 10-Gy X-ray treatment resulted in a linear regression line, almost parallel to that with paclitaxel alone, with a growth delay of about 6 days. In contrast, varying the X-ray dose with a constant paclitaxel injection (45 mg/kg b.w.) treatment showed some degree of synergism as the linear regression curves diverged. Interval time and sequence between paclitaxel administration and a 10 Gy X-ray treatment did not influence TGD. Protocols with paclitaxel at 30, 45, or 60 mg/kg were combined with radiation treatments at various doses (from 10 to 65 Gy). Values of TCD50 varied from 50.8 Gy for X-ray alone to 31.8 Gy for paclitaxel 60 mg/kg + X-ray. No differences were observed among MDD of different protocols. CONCLUSIONS: These results suggest that, under some conditions, paclitaxel combined with radiation can show superadditive effects and this result combined with the lack of severe normal tissue damage indicate that a favorable therapeutic gain can be obtained.

Animals↗
PubMed1998

Conservative surgery and radiotherapy in early stage breast cancer: a comparison between tumourectomy and quadrantectomy.

BACKGROUND AND PURPOSE: This study analyses and compares the results of local regional control, distant metastases and survival in two series of patients irradiated from 1986 to 1992 in our radiation oncology centre following quadrantectomy or tumourectomy for early stage breast cancer. MATERIALS AND METHODS: The quadrantectomy group consisted of 152 women, 109 (72%) with T1 and 43 (28%) with T2 tumours. Axillary nodes in this group were positive in 51 (33%) patients. The tumourectomy group included 123 women, 71 (58%) with T1 and 52 (42%) with T2 tumours. Positive axillary nodes were found in 56 (46%) of these patients. All quadrantectomy and tumourectomy patients received a dose of 50 Gy in 5 weeks to the whole breast, followed by a 10-16 Gy electron boost. Node positive patients in the tumourectomy group also received 50 Gy to the axillary apex and supraclavicular region. In both surgical groups, node positive premenopausal and postmenopausal patients received adjuvant CMF or tamoxifen therapy, respectively. RESULTS: After a median follow-up of 58 months, 89% of women in the tumourectomy group and 87% in the quadrantectomy group were alive and 80 and 73%, respectively, were free of disease. Breast and nodal failures were detected in 4.9 and 0.8% of cases, respectively, in the tumourectomy group, as compared to 5.9 and 3.3% of cases, respectively, in the quadrantectomy group. Distant relapses were observed in 16 and 18% of patients in the former and latter groups, respectively. Actuarial overall and disease-free survival was similar in the two series, with 5-year rates of 90 and 72%, respectively, in the tumourectomy group, and of 91 and 78%, respectively, in the quadrantectomy group. The differences in survival are not statistically different. CONCLUSIONS: Our findings show that tumourectomy and quadrantectomy, followed by adequate radiotherapy, provide comparable results in terms of local-regional control and survival.

Adult↗
PubMed1998

Radiotherapy with or without androgen deprivation in the treatment of localized adenocarcinoma of the prostate.

This study analyzes the results of disease relapse and survival in two series of patients treated between 1974 and 1991 with definitive irradiation, with or without early androgen deprivation, for carcinoma of the prostate localized to the pelvis. All 264 patients were irradiated to the prostate and pelvic lymph nodes with a dose of 50 to 54 Gy in 25 to 27 fractions, followed by a 16- to 20-Gy boost in 8 to 10 fractions to the prostate and periprostatic region. Ninety percent of patients received a total dose to the prostate (pelvis + boost) of 70 Gy. Ninety-nine of the 264 patients underwent early androgen deprivation. The endocrine manipulation program was initiated 0 to 9 months before the beginning of the radiotherapy course and was continued for 2 or more years or until disease progression. All patients who relapsed after radiotherapy alone received late hormonal manipulation. After a median follow-up of 100 months, no difference in the incidence of local and distant failure rate and cancer-specific mortality was detected between the two treatment groups. The local and distant failure rates were, respectively, 19% and 40% in patients who had undergone radiotherapy and early androgen deprivation and 20% and 36% in patients who received radiotherapy alone. Cancer mortality was similar, with 35% and 30% of deaths in the former and latter group, respectively. Death for intercurrent disease, however, was significantly more frequent (p = 0.03) in patients treated with radiotherapy and hormones (19%) than in those who received radiotherapy alone (8%). Actuarial analysis of both metastasis-free and disease-free survival detected no difference between the two treatment groups, with 10-year rates of 53.3% and 42.5%, respectively, in the radiation-alone group and 45.5% and 47%, respectively, in the radiation-plus-androgen deprivation group. A statistically significant difference (p = 0.03) in overall survival in favor of patients treated with radiotherapy alone was noted, with a 10-year rate of 47%, compared with 26% observed in the radiotherapy-plus-androgen deprivation group. In conclusion, results of our study confirm numerous reports based on retrospective analyses that failed to show any benefit of hormonal management adjuvant to a definitive irradiation. The disappointing finding was the significantly better overall survival in patients who underwent radiotherapy alone.

Adenocarcinoma↗
PubMed1997

Combined treatment of invasive bladder carcinoma with transurethral resection, induction chemotherapy, and radical radiotherapy plus concomitant protracted infusion of cisplatin and 5-fluorouracil: a phase I study.

BACKGROUND: The aim of this study was to define the maximum tolerated doses (MTDs) of cisplatin (CDDP) and 5-fluorouracil (5-FU) administered as protracted intravenous infusion (PVI) during hyperfractionated radiotherapy (HFRT) administered with organ-sparing intent to patients with infiltrating transitional cell carcinoma of the bladder (TCCB). METHODS: Twenty-five patients with T2-T4aNXM0 TCCB were enrolled in this study. After a complete transurethral resection, bladder mapping, and two cycles of induction chemotherapy, patients were submitted to HFRT and CDDP + 5-FU as concomitant PVI at escalating dose levels until MTDs were reached. Treatment efficacy was also evaluated, in terms of complete response (CR) rates and cystectomy free, disease free, and overall survival. RESULTS: Combined treatment was well tolerated. The recommended doses for Phase II studies of PVI chemotherapy and radiotherapy for patients with invasive bladder carcinoma are CDDP 5 mg/m2/day and 5-FU 220 mg/m2/day. Twenty-four patients were evaluable for response: 21 (87.5%) had CR and 3 PR. After a median follow-up of 31 months (range, 11-49 months), 18 of 21 patients with CRs (86%) were alive: 15 (71.4%) had tumor free bladder, of whom 3 had superficial recurrence successfully treated with endovesical therapy and 1 had distant metastases. Three patients were submitted to cystectomy, one for superficial recurrence and hematuria and two for invasive bladder recurrence. CONCLUSIONS: This study defines the MTDs of CDDP and 5-FU concomitantly administered with hyperfractionated radiotherapy. The low toxicity observed and the high CRs and bladder preservation rates deserve further study.

Aged↗
PubMed1995

Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology.

The value of hyperthermia as an adjuvant to radiotherapy in patients with malignant melanoma was studied in a European multicentre trial. 134 metastatic or recurrent lesions of malignant melanoma in 70 patients were randomly assigned to receive radiotherapy (three fractions of 8 Gy or 9 Gy in 8 days) alone or followed by hyperthermia (43 degrees C for 60 min). Overall, the 2-year actuarial local tumour control was 37 (SE 5)%. Univariate analysis showed a beneficial effect of hyperthermia (radiation alone 28% vs combined treatment 46%, p = 0.008) and radiation dose (24 Gy 25% vs 27 Gy 56%, p = 0.02), but no effect of tumour size (< or = 4 cm 42% vs > 4 cm 29%, p = 0.21). Cox multivariate regression analysis showed the most important prognostic variables to be hyperthermia (odds ratio for 2-year local control 1.73 [95% CI 1.07-2.78], p = 0.023), tumour size (0.91 [0.85-0.99], p = 0.05), and radiation dose (1.17 [1.01-1.36], p = 0.05). Addition of heat did not significantly increase acute or late radiation reactions. Heating was well tolerated, but because of difficulties with equipment only 14% of treatments achieved the protocol objective. The overall 5-year survival rate was 19%, but 38% of the patients for whom all known disease was controlled survived 5 years. Adjuvant hyperthermia significantly improved local tumour control when applied in association with radiation in treatment of malignant melanoma. Successful local treatment of patients with a single or a few metastatic malignant melanoma lesions has significant curative potential.

Adult↗
PubMed1995

Age and sex are independent predictors of 5-fluorouracil toxicity. Analysis of a large scale phase III trial.

BACKGROUND: Cancer is most common in older age groups, but little information is available with regard to the impact of age on chemotherapy toxicity. This study was undertaken to determine if age is an independent risk factor for 5-fluorouracil (5-FU) toxicity. METHODS: Toxicity data from a prospective, randomized, multiinstitution trial of 5-FU-based treatment for advanced colorectal cancer were analyzed. Toxicity for each organ system was graded. Individual organ toxicity proportions were compared using chi-square analysis. A logistic regression was performed using age (younger than 70 years vs. 70 years or older), sex, treatment arm, performance status, and length of therapy as model parameters to predict severe toxicity. Toxicity in 331 patients was analyzed. RESULTS: Advanced age was significantly associated with the occurrence of any severe toxicity (58 vs. 36%, P < 0.001), leukopenia (24 vs. 10%, P < 0.005), diarrhea (24 vs. 14%, P = 0.01), vomiting (15 vs. 5%, P = 0.01), severe toxicity in more than 2 organ systems (10 vs. 3%, P = 0.02), and treatment mortality (9 vs. 2%, P = 0.01). By univariate analysis, age (P < 0.001) and sex (P < 0.0001) were independent predictors of severe toxicity. Twenty-two of 27 women age 70 years or older had severe toxicity. CONCLUSIONS: Age 70 years or older and sex are risk factors for severe toxicity from 5-FU-based chemotherapy. Advanced age does not contraindicate the use of this type of chemotherapy, but close monitoring for multiple organ toxicities and vigorous supportive care of those with toxicity are required. Dosing decisions in older patients are difficult and must integrate assessments of organ function, comorbidities, overall physical status, and goals of treatment, in an effort to ensure the best possible outcome for these patients.

Age Factors↗
PubMed1995

Prognostic impact of transurethral resection on patients irradiated for localized prostate cancer.

The prognosis for irradiated patients with localized prostatic carcinoma following transurethral resection of the prostate (TURP) has been debated. Controversy centers upon whether or not TURP has an adverse effect on the outcome. A retrospective analysis of 264 patients treated during 1974-1991 with radical external beam radiotherapy was performed. Ten patients who were irradiated postoperatively were excluded. One hundred and nine patients with urinary obstruction underwent TURP. In another 155 patients, pathological diagnosis was made by needle aspiration or tru-cut biopsies. One hundred and one patients received endocrine manipulation, 58 (40%) in the needle biopsy group, and 43 (39.5%) in the TURP group. Lymph node staging by pelvic lymphadenectomy (20 cases), lymphangiography (15 cases), and CAT and/or NMR (113 cases) was performed in 148 patients. Nodal metastases were found in 38 patients, 19 in the needle biopsy group, and 19 in the TURP group. Disease-related, disease-free and metastasis-free survivals were calculated for all stages and within each tumor stage and histological grade for both groups. Correlation of pretreatment factors with clinical outcome was evaluated by multivariate analysis. Overall, disease-related survival was significantly higher (P = 0.05) in patients undergoing needle biopsy than in those who had TURP (58% vs. 38% at 10 years). This difference was more significant in the subset of patients with well differentiated tumors (P < 0.01). However, no difference could be observed between the two groups in histological grade 2 and 3 tumors or by stage comparison.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

The EORTC randomized trial on three fractions per day and misonidazole (trial no. 22811) in advanced head and neck cancer: long-term results and side effects.

From 1981 to 1984, a randomized study was done by the EORTC Radiotherapy Group comparing a fractionation schedule with three fractions per day (multiple fractions per day, MFD), with or without misonidazole, to conventional fractionation. The aim of the study was to obtain improved local and regional control and survival by shortening of the treatment time in the first 2 weeks of irradiation. Three fractions of 1.6 Gy/day (4-h interval) were given during 10 irradiation days to a total of 48 Gy. After 3-4-weeks interval, a boost was given to 67.2 or 72 Gy also in three fractions per day. This schedule was compared to an identical arm with misonidazole 1 g/m2/day and a third arm with conventional fractionation (70 Gy in 35 fractions, 7 weeks or 75 Gy in 44 fractions, 9 weeks). A total number of 523 patients was included in the study. Acute mucositis was much heavier in patients treated with three fractions per day (Van den Bogaert et al. Int. J. Radiat. Oncol. Biol. Phys. 8: 1649-1655, 1982). Early results, communicated in 1986 (Van den Bogaert et al. Int. J. Radiat. Oncol. Biol. Phys. 12: 587-591, 1986) showed no differences in treatment outcome between the three treatment arms. Long-term results and data on late effects are now available. Survival at 5 years was 18% (SE 1.9%) and locoregional control was 27% (SE 2.9%). No statistically significant differences could be observed between the three treatment arms.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1995

The EORTC randomized trial on three fractions per day and misonidazole in advanced head and neck cancer: prognostic factors.

In trial no. 22811 on a randomized comparison of multiple fractions per day (MFD), with or without misonidazole, to conventional fractionation in advanced head and neck cancer, a large number (523) of patients was entered in a short period of time. No differences in treatment results were obtained, but the study created an important database, allowing for detailed evaluation of the most important factors influencing prognosis. In univariate analysis, factors significantly influencing survival and locoregional control were: performance status, histological differentiation, tumor site, tumor and nodal staging, and tumoral and nodal volume. In multivariate analysis, significant factors for survival were nodal involvement, tumor stage, performance status, and tumor site. Significant factors for locoregional control were nodal involvement and total tumor burden. This analysis suggests that total tumor burden (volume) should be included in the interpretation of treatment results in head and neck cancer.

Combined Modality Therapy↗
PubMed1995

Combination goserelin and tamoxifen therapy in premenopausal advanced breast cancer: a multicentre study by the ITMO group. Italian Trials in Medical Oncology.

It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer.

Adult↗