Biomedical subjects

P Pronzato

Publications and source records attributed to P Pronzato.

At least 19 recordsLinked to original sources

PubMed2006

Adjuvant systemic treatment of early breast cancer: the NORA study.

BACKGROUND: Despite recommendations contained in international guidelines, factors such as the type of oncology centre, geographic distribution and the introduction of scientific advances into clinical practice can influence the choice of recommended treatment for early breast cancer. The NORA study is a prospective, longitudinal cohort study aimed at investigating tumour characteristics, treatment modalities, and other factors that influence therapeutic choices in early breast cancer patients who have undergone mastectomy or breast-conserving surgery (BCS). PATIENTS AND METHODS: From January 2000 to early 2004, we collected data on methods of cancer diagnosis, type of surgery and adjuvant medical treatment administered to the first 10 consecutive patients treated in 2000-2002 and the first 20 consecutive patients in 2003 and 2004 at 71 oncology centres in Italy, with the approval of the ethical committee at each centre. RESULTS: Approximately one-quarter of the cases (26.5%) were detected through screening programmes. BCS was performed in 63.7% and sentinel node biopsy (SNB) occurred in 11.1% of the patients. Of the 3515 total cases, 56.5% were node-negative. Grade 2 cancers comprised 51.3%, and 66.2% were hormone-receptor positive (ER+/PgR+). Chemotherapy (CHT) followed by hormone therapy (HT) was the most prescribed treatment (48.5%). CHT was mainly anthracycline-based (52.9%) and most patients received tamoxifen alone (77.7%) or after CHT (85.2%). For node-negative patients, HR+ and menopause status are the factors influencing the choice to add HT after CHT; patients with HR+ and pT4 tumours are more likely to receive HT instead of CHT. In node-positive patients, the addition of HT is influenced by HR+ status, the opportunity to have HT instead of CHT, and menopause. CONCLUSIONS: NORA is the first large cohort study to describe the factors that influence therapeutic choices in early breast cancer. Understanding these findings can help physicians in daily clinical practice.

Adult↗

PubMed2006

First line chemotherapy of metastatic breast cancer.

In the last 20-30 years the approach to metastatic breast cancer by chemotherapy has been largely studied. Anthracyclines, taxanes and, more recently, capecitabine and gemcitabine represent the breakthrough of treatment. In the next future the combination of chemotherapy and target therapy will be considered more frequently.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Relationship between human mammaglobin mRNA expression in breast cancer tissue and clinico-pathologic features of the tumors.

Human mammaglobin (hMAM) has recently been recognized as a breast associated glycoprotein. Although the biological role of hMAM is unknown, it has been previously reported that hMAM gene expression is a marker of low biological and clinical aggressiveness of breast cancer (BC). In this study, 148 cases of BC tissues were investigated for hMAM mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). In order to evaluate its prognostic value, hMAM was correlated with age of patients, type and size of tumor, nodal stage, histologic grade, c-erbB-2 over expression, Ki67 labelling index, estrogen receptor (ER) status and progesterone receptor (PGR) status. Fisher's exact test was used to examine the association between different parameters and hMAM. hMAM was expressed in 138/148 (93%) of BC tissues examined. Among the 10 hMAM negative cases, 8 were invasive ductal carcinomas (microscopically higher G3 grade) and 2 infiltrating lobular carcinomas. We found a significant association (p = 0.020) between absence of hMAM mRNA and G3 histologic grade but not with any other prognostic parameters studied. The present study indicates that lack of hMAM expression is restricted to the BC with G3 grading. Further studies are needed to clarify the biological basis and the clinical significance of our results.

Adult↗

PubMed2005

Hormonotherapy of advanced prostate cancer.

More than two decades of studies on hormonal treatment of Prostate Cancer are briefly reviewed. Recent American Society of Clinical Oncology recommendations have pointed the major issues faced in randomized clinical trials and meta-analyses. Androgen ablation remains the mainstay of treatment for advanced stages, while Docetaxel based chemotherapy is becoming the standard in hormonorefractory tumors and targeted therapies are approaching.

Androgen Antagonists↗

PubMed2005

Human mammaglobin mRNA is a reliable molecular marker for detecting occult breast cancer cells in peripheral blood.

Occult carcinoma cells in peripheral blood of breast cancer (BC) patients is generally associated with poor disease prognosis. Reverse transcriptase-polymerase chain reaction (RT-PCR) is a sensitive method for revealing rare circulating cancer cells. The target mRNA must be carefully chosen, as it must be expressed only by malignant cells. In this study, we developed a nested RT-PCR assay for mammaglobin (hMAM) and assessed both its specificity and its sensitivity in the detection of cancer cells in peripheral blood of BC patients. hMAM mRNA was detected by RT-PCR in 156/165 (95%) of fresh BC tissues analyzed. All samples from 66 healthy blood donors and 151 patients with benign breast disease were hMAM negative as assessed by nested RT-PCR. In contrast, hMAM was detected in 16/137 (12%) of peripheral blood samples deriving from BC patients: 0/9 in stage 0, 1/50 (2%) in stage I, 3/33 (9%) in stage II, 1/18 (5%) in stage III and 11/27 (41%) in stage IV. Using nested RT-PCR, we were able to amplify hMAM transcript of one tumour cell/10(6) normal cells. Our data demonstrate that hMAM mRNA detection by RT-PCR is a specific assay potentially suitable for identification of occult cancer cells in peripheral blood of BC patients.

Biomarkers, Tumor↗

PubMed2004

Patterns of relapse and modalities of treatment of breast cancer: the 'IRIS' Project, a multicenter observational study.

OBJECTIVES: The aim of this study was to describe the patterns of breast cancer relapse and the factors influencing therapeutic choices in an unselected postmenopausal population. METHODS: Five hundred and thirty-nine patients were enrolled between October 1999 and March 2001. The majority (92.6%) underwent surgery for the primary tumor: there was no difference between general and university hospitals in terms of the type of mastectomy, but a slight difference was found between Southern and Northern Centers. RESULTS: At the time of first relapse, 61.6% of the patients had a good Karnofsky performance status. The median disease-free interval (DFI) was 34 months. More than half of the patients (62.3%) presented a single metastasis. Metastatic disease was treated with chemotherapy in 64.8% of cases (alone in 44.1%, and in combination with hormone therapy in 20.1%), hormone therapy alone was given in 30.8% of cases. The main reasons for choosing chemotherapy were age (31%), standard guidelines (19.4%) and the site of metastatic disease (14.3%), and those for selecting hormone therapy were age (26.6%), site of relapse (19.3%), standard guidelines (19.2%), biological tumor characteristics (14.3%) and the DFI (11.1%). Taxane-containing treatments accounted for 46.1% of the chemotherapies, whereas letrozole was the preferred hormone (41.2%). CONCLUSION: The first relapse of breast cancer is often single, at bone or viscera, and mainly diagnosed by instrumental screening examinations. The preferred chemo- and hormone therapies are taxane-containing regimens and letrozole, respectively.

Antineoplastic Agents, Hormonal↗

PubMed2002

Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study.

BACKGROUND: Hot flashes are frequent in postmenopausal breast cancer patients, especially when treated with tamoxifen. Estrogen replacement therapy is the most effective treatment for hot flashes, but its use is controversial in breast cancer survivors. Progestins may offer a good alternative for the control of hot flashes in this setting; in particular, oral megestrol acetate has been proven effective in a randomized, placebo-controlled clinical trial. With the aim of further improving these results, we have designed a randomized study comparing oral megestrol acetate with depot intramuscular (i.m.) medroxyprogesterone acetate (MPA) for the control of hot flashes in postmenopausal patients with a history of breast cancer. PATIENTS AND METHODS: Seventy-one postmenopausal patients were randomized to receive an i.m. injection of depot MPA 500 mg on days 1, 14 and 28, or oral megestrol acetate 40 mg daily for 6 weeks. Patients recorded daily the number and severity of their hot flashes; response was defined as a > or =50% decrease in the number and severity of hot flashes. RESULTS: At week 6, hot flashes were reduced by 86% on average in the whole group of patients, without significant differences between the two progestins. Response was obtained by 75 and 67% of patients receiving MPA or megestrol, respectively (P = 0.5). Responders were followed to assess maintenance of response (without further treatment), which was significantly better with i.m. MPA: in this group, 89% of responders still showed a benefit at week 24, compared with 45% in the megestrol group (P = 0.03). CONCLUSIONS: Our study shows that a short cycle of i.m. depot MPA injections provides significant and long-lasting relief from postmenopausal hot flashes in patients with a history of breast cancer, offering an alternative to estrogen replacement therapy or prolonged administration of oral megestrol.

Administration, Oral↗

PubMed2002

A dose finding study of carboplatin and gemcitabine in advanced non-small cell lung cancer.

The excellent activity of the cisplatin-gemcitabine combination and favorable toxicological profile of carboplatin are the basis of carboplatin-gemcitabine combination therapy for non-small cell lung cancer. We carried out a dose-finding study with the aim of establishing the maximum tolerated dose (MTD) of carboplatin on day 1 in combination with gemcitabine at the dose of 1000 mg/m2 on days 1 and 8 in a 21-day cycle. The starting dose level for carboplatin was the area under the concentration time curve (AUC) 4 mg/ml/min. 18 patients were treated and a dose limiting toxicity was observed in 2 cases at the level of AUC 6 mg/ml/min. AUC 5 mg/ml/min was considered as the MTD for carboplatin in our regimen. Notably, 7 objective responses were observed.

Aged↗

PubMed2001

Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group.

PURPOSE: To evaluate whether an accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) chemotherapy regimen with the support of granulocyte colony-stimulating factor (G-CSF) induces a higher activity and efficacy compared with standard CEF in metastatic breast cancer patients. PATIENTS AND METHODS: Stage IV breast cancer patients were randomized to receive as first-line chemotherapy either standard CEF (cyclophosphamide 600 mg/m(2), epirubicin 60 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 21 days (CEF21) or accelerated-intensified CEF (cyclophosphamide 1,000 mg/m(2), epirubicin 80 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 14 days (HD-CEF14) with the support of G-CSF. Treatment was administered for eight cycles. RESULTS: A total of 151 patients were randomized (74 patients on the CEF21 arm and 77 on the HD-CEF14 arm). In both arms, the median number of administered cycles was eight. The dose-intensity actually administered was 93% and 86% of that planned, in CEF21- and HD-CEF14-treated patients, respectively. Compared with the CEF21 arm, the dose-intensity increase in the HD-CEF14 arm was 80%. Both nonhematologic and hematologic toxicities were higher in the HD-CEF14 arm than in the CEF21 arm. During chemotherapy, four deaths occurred in the HD-CEF14 arm. No difference in overall response rate (complete plus partial responses) was observed: 49% and 51% in the CEF21 and HD-CEF14 arms, respectively (P =.94). A slightly non-statistically significant higher percentage of complete response was observed in the HD-CEF14 arm (20% v 15%). No difference in efficacy was observed. The median time to progression was 14.3 and 12.8 months in the CEF21 and HD-CEF14 arms, respectively (P =.69). Median overall survival was 32.7 and 27.2 months in the CEF21 and HD-CEF14 arms, respectively (P =.16). CONCLUSION: In metastatic breast cancer patients, an 80% increase in dose-intensity of the CEF regimen, obtained by both acceleration and dose intensification, does not improve the activity and the efficacy compared with a standard dose-intensity CEF regimen.

Adult↗

PubMed2001

Anthracyclines in non-small cell lung cancer.

The literature concerning the use of anthracyclines in the treatment of non-small cell lung cancer (NSCLC) is reviewed here. Overall, the activity of doxorubicin (DOXO) is unsatisfactory, whereas, the analogous epidoxorubicin (EPI) yields a 30% response rate (RR) when administered at intermediate-high doses. All active drugs, including EPI, should be considered to design the most active combination. Mainly, in the setting, in which an objective response is very important, for instance the neo-adjuvant pre-operatory setting.

Antibiotics, Antineoplastic↗

PubMed2001

Thymidine labeling index analysis in early breast cancer patients randomized to receive perioperative chemotherapy.

OBJECTIVE: To identify through a substudy of a larger, multicenter study of adjuvant treatment in primary operable breast cancer patients any possible correlation between cellular proliferation rate, measured by thymidine labeling index (TLI), and perioperative chemotherapy (periCT). METHODS: TLI was measured in slices of early breast carcinoma patients. The main trial was designed to randomize patients after primary surgery to receive one cycle of periCT consisting of cyclophosphamide, epidoxorubicin and 5-fluorouracil, or no periCT. RESULTS: Of 600 patients randomized into the main study, 197 were eligible for inclusion in this substudy. Characteristics of patients were quite similar to those of the entire population entered into the main study. The TLI cutoff value in our series was 0.7% expressed as the median percentage ratio of thymidine-labeled cells undergoing DNA synthesis in the tumor cell population of specimens from the 197 patients. No differences were observed in terms of relapse-free survival (RFS) and overall survival (OS) after grouping the patients by TLI value (low and high) and by treatment. Among node-negative patients, a significant improvement in terms of OS (p = 0.02), but not RFS (p = 0.06), was seen in patients with a high-TLI value who underwent periCT versus controls. CONCLUSIONS: TLI may be a useful tool for the identification of node-negative patients with high-TLI values who may benefit from periCT.

Adult↗

PubMed2001

A three-drug regimen (gemcitabine, ifosfamide and cisplatin) for advanced non-small-cell lung cancer.

We have carried out a pilot study on 25 non-small cell lung cancer patients, administering the combination of gemcitabine at the dose of 1000 mg/m2 on days 1 and 8, ifosfamide 1500 mg/m2 on days 1 and 2 (plus mesna as uroprotector) and cisplatin 40 mg/m2 on days 1 and 2, every 21 days. Granulocyte Colony Stimulating Factor was employed in all cases from day 10 to day 18 at the dose of 300 microg daily. An objective response was observed in 11 cases (44%). The regimen was active, but toxicity was remarkable with some cases of severe myelosuppression and mucositis.

Aged↗

PubMed2001

[Prevalence of anemia in oncologic patients treated with chemotherapy. Italian survey at the national level].

UNLABELLED: In Italy the prevalence of anemia in cancer patients has only been indirectly drawn from clinical studies, and a direct estimation has never been made. METHODS: This is the first nation-wide survey on the prevalence of anemia in cancer patients in Italy. In 193 Centres, clinical data were collected on consecutive patients with non-myeloid malignancies entering a new cycle of chemotherapy during a reference week in 1997. RESULTS: A total of 1763 patients has been recruited. At the time of enrollment grade I-II anemia was observed in 56% of patients, although only 1% showed severe anemia. Most of the patients (73%) experienced a decrease of haemoglobin level following treatment completion. Drop of haemoglobin correlated with a more advanced stage of the disease and with a lower performance status at baseline. CONCLUSION: Anemia is an increasingly common complication in cancer patients undergoing chemotherapy. Improving our knowledge on occurrence of anemia and the type of neoplasms and chemotherapies which are more likely to be associated with this complication may allow the adoption of specific measures to prevent the development of anemia and to avoid the need of blood transfusion in these patients.

Anemia↗

PubMed2000

Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin.

Metastatic breast cancer remains an incurable disease and the median overall survival has not significantly improved over the past two decades. Aims of the present randomized phase II trial were to analyse activity and toxicity of chemotherapies with single agent or with combination regimens in previously treated patients with advanced breast cancer. Ninety-nine eligible patients were randomized to receive the following chemotherapies: Arm A - vinorelbine 30 mg/m2 i.v. weekly; Arm B - leucovorin 100 mg/m2 i.v. followed by 5-fluorouracil 370 mg/m2 i.v. days 1 --> 5, q 28 days; Arm C - mitoxantrone 12 mg/m2 i.v. only day 1 + leucovorin 100 mg/m2 i.v. followed by 5-fluorouracil 370 mg/m2 i.v. days 1 --> 3, q 28 days. Patients characteristics are comparable in the three groups. The median number of chemotherapy courses administered was 7, 6 and 5 in arm A, B and C, respectively. Objective responses were 24%, 30% and 21% and the median duration of responses were 2, 2.5 and 5.5 months in the arm A, B and C, respectively. Median overall survivals were 9.5, 9 and 9 months in the three arms. No difference was noted comparing the survivals of responding or non responding patients. General toxicity was not mild, with 27.5% of patients experiencing WHO grade 3-4 toxicities. Our results are similar in the three groups of patients and comparable to those reported by other authors. Chemotherapy applied to patients with second or subsequent recurrence allow objective responses in a small percentage of patients. Moreover responders have a negligible prolongation of survival.

Adult↗

PubMed1999

A phase II study of a three-drug combination (cisplatin, ifosfamide and vinorelbine) plus granulocyte-colony stimulating factor in advanced non small cell lung cancer.

Twenty-nine patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of cisplatin 20 mg/m2 days 1-3, ifosfamide 1500 mg/m2 days 1-2 (plus mesna as uroprotector) and vinorelbine 25 mg/m2 days 1 and 5; filgrastim was given at the dose of 300 microg subcutaneously from day 8 to day 15. A response rate of 28% was observed. The activity of this combination in an outpatient setting, with acceptable toxicity, has been demonstrated.

Adult↗

PubMed1998

High-dose-intensity combination chemotherapy for advanced sarcomas: a pilot study.

A new polychemotherapy schedule involving high dose intensity and shortened intervals has been developed for patients with advanced sarcomas. Mesna at 2500 mg/m2 for 3 days, epidoxorubicin at 60 mg/m2 on day 1, ifosfamide at 2500 mg/m2 for 3 days, and dacarbazine at 450 mg/m2 for 2 days were given every 2 weeks to a consecutive series of 20 patients. All patients received granulocyte colony-stimulating factor (G-CSF; Filgrastim) subcutaneously at 300 microg from day 5 to day 12 of each cycle. The treatment was feasible and toxicity was acceptable, with grade IV myelotoxicity being observed only in one case. In all, 6 of 14 evaluable patients had an objective response; the median survival was 12 months. Toxicity was milder than that observed for the classic combination MAID, and the planned dose intensity was maintained in the majority of cases.

Adult↗

PubMed1998

High-dose intensity cyclophosphamide, epidoxorubicin, vincristine and prednisone by shortened intervals and granulocyte colony-stimulating factor in non-Hodgkin's lymphoma: a phase II study.

Twenty patients with non-Hodgkin's lymphoma were treated with a combination of cyclophosphamide (750 mg m(-2), day 1), epidoxorubicin (60 mg m(-2), day 1), vincristine (1.4 mg m(-2), day 1) and prednisone (100 mg m(-2), days 1-5) every 14 days. Shortening of intervals was associated with the prophylactic employment of granulocyte colony-stimulating factor (G-CSF; specifically, filgrastim) administered at a dose of 300 microg subcutaneously from day 6 to day 11. The ratio between actually delivered dose intensity and planned dose intensity was 1.0 in 18 out the 20 patients. Toxicity was acceptable; response rate and survival are in the expected range. The present study demonstrated the feasibility of acceleration of chemotherapy cycles to obtain dose intensification in non-Hodgkin's lymphoma.

Adult↗

PubMed1998

A phase II trial of carboplatin, methotrexate and fluorouracil in fluorouracil-pretreated colorectal cancer.

5-Fluorouracil and leucovorin combination is the most commonly applied chemotherapy treatment for colorectal cancer patients, both in the adjuvant setting and for advanced disease. Patients resistant or refractory to the 5-fluorouracil-leucovorin combination have been treated in this phase II trial with carboplatin plus methotrexate and fluorouracil in sequence. Twenty patients with measurable lesions from advanced colorectal cancer were entered in the trial. The treatment plan was carboplatin 300 mg/m2 day 1, methotrexate 40 mg/m2 day 1, fluorouracil 600 mg/m2 day 2, every 21 days. Two patients with liver metastasis had a partial response. Median survival was 12 months (range 4-24). Toxicity was acceptable and no patient had to be hospitalized because of the treatment. In this set of patients activity of the new combination is marginal.

Aged↗