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Biomedical subjects

A Durando

Publications and source records attributed to A Durando.

At least 19 recordsLinked to original sources
PubMed2006

Multicenter phase II study of trastuzumab in combination with epirubicin and docetaxel as first-line treatment for HER2-overexpressing metastatic breast cancer.

The primary objective of study is to evaluate cardiac safety of trastuzumab in combination with epirubicin and docetaxel. HER2-overexpressing metastatic breast cancer patients were enrolled in a two-stage, multicenter phase II trial with weekly trastuzumab (4 and then 2 mg/kg) with epirubicin and docetaxel (either 75 mg/m(2)) on day 1 every 3 weeks. After eight courses of chemotherapy, trastuzumab was continued as a single agent. To assess cardiotoxicity, patients were evaluated for left ventricular ejection fraction (LVEF) at baseline, every two cycles during chemotherapy and trastuzumab, and every 3 months during trastuzumab alone. Cardiotoxicity was defined as signs and/or symptoms of congestive heart failure (CHF) and/or an absolute decrease in LVEF of >or=20 units or a decline to <or=45%. In the first stage of the study, three episodes of cardiotoxicity were observed (two asymptomatic declines of LVEF and one CHF) in 29 patients, and recruitment continued. During follow-up of patients who continued trastuzumab after chemotherapy, seven further cardiologic events occurred (three asymptomatic decline of LVEF and four CHF). Therefore, recruitment was interrupted after the 45th patient. The majority of cardiac events occurred late during trastuzumab alone, half were asymptomatic and all cases of CHF were resolved using cardiac therapy. Complete and partial responses were 20 and 47%, respectively, and the median time to progression was 15.7 months (95% CI, 11.6-19.0 months). In light of the cardiotoxicity experienced during this study, we currently recommend that this combination be used only in controlled clinical trials under vigilant cardiac monitoring.

Adult↗
PubMed2006

Concurrent radiotherapy does not affect adjuvant CMF delivery but is associated with increased toxicity in women with early breast cancer.

We evaluated whether concurrent radiotherapy (RT) affected delivery and toxicity of adjuvant intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) in women with operable breast cancer. The medical charts of 321 consecutive breast cancer patients who received CMF either alone for 6 cycles, or for 4 cycles following of an anthracycline (A-CMF) were reviewed. One hundred forty-four women underwent radiotherapy concurrently with CMF. Optimal CMF delivery (success as opposite to failure) was defined as the combined achievement of an average relative dose intensity (aRDI) > or = 85% and an average percent of the total dose (aPTD) > or = 90% for the three drugs in the CMF regimen. Multivariate logistic regression analysis showed that concurrent-RT did not affect CMF delivery (OR for success 1.391 p=0.230). The sequential A-CMF regimen (OR for success 0.208, 95% C.I. 0.120-0.360, p<0.001) and age > or = 56 (OR for success 0.351, 95% C.I. 0.200-0.161, p<0.001) were independently associated with suboptimal CMF delivery. Moreover, concurrent RT was independently associated with increased leukopenia, thrombocytopenia, upper abdominal pain, mucositis and fatigue. Our retrospective analysis suggests that concurrent-RT has no impact on optimal CMF delivery, but it increases the burden of CMF-related toxicity.

Adult↗
PubMed2004

[Biologic therapy and epithelial ovarian cancer].

The identification of new molecular prognostic and predictive factors for ovarian cancer may contribute in deciding individual therapeutic strategies; on the other hand, there has been growing interest in new biologic therapies to correct molecular or genic lesions of neoplastic cells (genic therapy), or to activate the specific immune response (immunological therapy). Chemotherapy collateral toxic effects, as myelotoxicity, should be reduced through transfection of genes that modulate drug resistance in stem cells. The data at present available suggest then the potential role of these new treatments, are more specific and less toxic than current therapies; however, other biological-molecular studies are required to obtain the clinical applications of the results: Aim of this study is to provide a review of the most interesting data in ovarian cancer biologic therapy.

Animals↗
PubMed2000

Evidence for a dose-response effect between p53 (but not p21WAF1/Cip1) protein concentrations, survival, and responsiveness in patients with epithelial ovarian cancer treated with platinum-based chemotherapy.

The prognostic values of p53 and of its downstream mediator p21WAF1/Cip1 in patients receiving adjuvant chemotherapy for epithelial ovarian cancer have not been clearly established. Tumor extracts from a series of 120 patients treated postsurgically with cisplatin or carboplatin alone or together with other chemotherapeutics for primary ovarian carcinoma were assayed both for p53 protein by an immunofluorometric assay developed by us and for p21 protein by a commercially available immunoassay. Relative risks (RRs) for cancer relapse and death after 24 months of follow-up were determined by multivariate Cox regression analysis. Disease-free (DFS) and overall survival (OS) probabilities were also examined by the Kaplan-Meier method and log-rank tests. All other procedures were similarly nonparametric and based on two-sided tests of significance. Concentrations of p53 were elevated in patients with advanced stage disease (P = 0.02) or poorly differentiated (P = 0.03), suboptimally debulked tumors (P = 0.02), as well as in patients who failed to respond to chemotherapy (P = 0.03), as assessed by computed tomography scanning, serum CA125 determination, and second-look laparotomy. Statistically significant associations between concentrations of p53 and p21 were not found, nor were relationships demonstrated between concentrations of p21 and other clinicopathological variables or treatment response. Univariate analysis showed that p53 concentrations above the median indicated significantly higher risks for relapse (P = 0.04) and death (P < 0.01) and showed trends for increasing risks for relapse (P = 0.04) and death (P < 0.01) when p53 was considered as a four-level categorical variable. Multivariate analyses adjusted for age, stage, grade, and residual tumor size confirmed these observations (RR = 1.50; P = 0.05 for DFS and RR = 1.92; P = 0.03 for OS) for median-dichotomized p53, but the trends were of borderline significance (P = 0.09 for DFS and P = 0.07 for OS). In contrast, p21 positivity was not a significant predictor of favorable outcome in univariate survival analysis, and use of a three-level variable combining positivity or negativity status for both p53 and p21 did not yield greater separation of patients into risk groups (P = 0.07 for DFS and P = 0.06 for OS) than the use of p53 alone. Assessment of p53 expression may be an independent indicator of poor prognosis in ovarian cancer patients treated with adjuvant chemotherapy. The prognostic value of p21 expression, however, could not be demonstrated in our series of ovarian cancer patients.

Adult↗
PubMed1998

Flow cytometry in breast cancer: prognostic and surgical indications of the sparing of axillary lymph node dissection.

The lymph node status is still regarded as the most important prognostic factor in breast cancer. However, the utility of axillary lymph node dissection in clinically node-negative patients with breast cancer as a therapeutic approach rather than a pathologic staging procedure has been recently discussed. DNA index (DI) and S-phase fraction (SPF), evaluated by flow cytometric analysis, are two prognostic factors used especially in the assessment of the adjuvant therapy in stage N0 tumors. By studying a large number of cases, the authors aimed to assess the potential role of flow cytometry in predicting lymph node status. Two hundred eleven patients with breast cancer were included. Each tumor specimen was freshly analyzed by flow cytometry to assess DI and SPF. The authors also evaluated TNM status of patients, estrogen- and progesterone-receptor (ER and Pgr) status, and histologic grades. A group of patients with negative axillary lymph nodes was identified by means of association of tumor size of 2 cm or less, DI of 1, and SPF less than 7%. The ER and PgR status as well as histologic grade were significantly more favorable in this group of patients. These findings indicate that association of DI, SPF value, and tumor size may be predictive of axillary lymph node status in breast cancer.

Axilla↗
PubMed1997

Carboplatin plus etoposide regimen in advanced breast cancer. A phase II study.

Carboplatin is used in many kind of tumors with similar results to cisplatin but without the same toxicity. We decided to use it, in combination with etoposide, for metastatic breast cancer. Eighteen women with advanced breast disease entered this phase II study. Each of them received, every 28 days, carboplatin on day 1, at a dose calculated with the Calvert formula, and etoposide on days 1, 2, 3 at a dose of 100 mg/m2. For 12 women this treatment was the first-line chemotherapy, while for the other six it was the second-line therapy, after the administration and the failure, in 4 cases out of 6, of regimens based on anthracycline. In each group we obtained an objective response of 50%, with a complete response of 25% in the first and of 33% in the second. On the whole, 11 patients died (one not from the disease) (10/18, 55%). Toxicity was extremely mild, with only one patient with grade III anemia. Our data suggest that a carboplatin/etoposide combination could be active and well-tolerated in patients with metastatic breast cancer, but the few number of patients in this study makes further research necessary for confirmation.

Adult↗
PubMed1991

[Cervical endoscopy for rational colposcopic evaluation].

Having analysed the results of a large series of patients, the Authors propose endocervical examination as a vital step to be performed at the same time as colposcopy or, in certain well identified cases, following cytohistological results. Endocervical examination either before or after colposcopy is then described in a protocol taking into account the various parameters. The most important are: the assessment of the squamocolumnar line, the type of colposcopic lesion, and cytohistological findings. Following a brief discussion of traditional diagnostic tests (endocervical curettage, endocervical observation using Kagan forceps), the Authors underline the importance of the endocervicoscope which allows a closer, noninvasive and precise evaluation to be made.

Cervix Uteri↗
PubMed1991

[Clinical aspects of pelvic histangiopathies. New therapeutic possibilities with danazol].

Menometrorrhagia and hypermenorrhoea are often present in patients who also suffer from a state of insufficiency of the utero-adnexal venous system interpretable as a clinical entity of system pathology and accompanied by pictures of acquired venous ectasis. The lack of any easy clinical characteristic objectivisation often prevents easy recognition and complex diagnostic investigation is therefore indispensable. Treatment is often destructive surgery following the failure of the various medical or conservative surgical therapies that are tried. Personal experience in cases in which the clinical picture (big uterus, menometrorrhagia, pelvic pain) presents a pathology of the venous vascular system, can report considerable benefit first and disappearance later of the symptomatology, with treatment using danazol at a dose of 200-300-400 mg/die. This makes demolition surgery, which is not often well accepted by the patient, inopportune.

Adnexa Uteri↗
PubMed1990

[Intra-lesional beta-interferon in combination with systemic thymopentin. Evaluation of results in 35 cases of CIN III and 2 cases of VAIN associated with HPV].

We performed an open study on 37 patients (average age 35 years), with CIN III or VAIN III and Viral Cytopatic Effects (VCE), who underwent a new standardized bifasic therapy by means of intralesional beta-interferon, topic beta-interferon and subcutaneous timopentine injection. Each therapeutic and checking step was made by colposcopic and microcolpohysteroscopic inspection, which showed spreading necrotic zones in the dysplastic places and peripheral typical epithelium replacement. Microcolpohysteroscopy allowed us to obtain correct diagnosis of the lesion and its location, to discriminate each pathologic aspects (CIN, VAIN, VCE), to perform an adeguated biopsy and intralesional therapy and to follow-up lesion course without repeated biopsies. After two months of therapy as maximum safety limit, we performed conization (in CIN case) in order to confirm the effects of therapy by hystology and especially to evaluate the deep lesional border. The istologic examination underlined the previous microcolpohysteroscopic report of dysplastic regression until its disapperance, with lasting VCE in all the cases.

Adjuvants, Immunologic↗
PubMed1989

[Uterine hypoplasia and infertility].

On the basis of reported data, uterine hypoplasia is analysed from the morphological as well as the functional viewpoint (myo-endometrial receptivity and reactivity and ovarian vascularisation) through the routine use of two new methods of diagnosis: laparoscopy and hysteroscopy. Following the study of the relations between uterine hypoplasia and infertility, it is concluded that a precise therapeutic protocol should be laid down after correct diagnostic procedure.

Female↗
PubMed1981

Generation of CFU-C/suppressor T cells in vitro: an experimental model for immune-mediated marrow failure.

T cells were derived from the bone marrow of 8 healthy donors and fractionated, according to their receptors for the Fc fragment of IgG, into TG+ and TG- lymphocytes. These were then cocultured with autologous or allogeneic bone marrow cells in agar in the CFU-C assay. No significant suppresion of colony formation could be detected. Total T, TG+, and TG- cells were then incubated for 18 hr with PWM, washed, and cocultured with bone marrow cells. PWM-treated TG- cells showed no significant CFU-C suppressor activity, whereas PWM-treated total T and TG+ cells inhibited colony formation of both autologous and allogeneic marrow cells. The supernatant of PWM-treated total T and TG+ cells also inhibited colony formation. PWM alone enhanced colony formation. The results of this study indicate that normal T cells can be activated in vitro to become CFU-C/suppressor cells after PWM stimulation, and that this effect is mediated by T cells with the Fc receptor for IgG.

Bone Marrow Cells↗
PubMedDate not supplied

Independent factors predict supranormal CA 15-3 serum levels in advanced breast cancer patients at first disease relapse.

Data currently available are insufficient to demonstrate a real utility for CA 15-3 in the diagnosis, staging or surveillance of breast cancer patients following primary treatment. The aim of this study was to determine if there was a correlation between supranormal CA 15-3 serum levels and clinical and biological variables in breast cancer patients at first disease relapse. From October 1988 to March 1998, 430 consecutive patients entered the study. Overall CA 15-3 sensitivity was 60.7%. Elevated CA 15-3 levels were found more frequently in patients with liver metastases (74.6%) and in those with pleural effusion (75.7%). CA 15-3 sensitivity was 70.4% in patients with estrogen-receptor-positive (ER+) primary tumors and 45.9% in those with estrogen-receptor-negative (ER-) tumors (p < 0.0001). In patients with a limited extent of disease, marker sensitivity was 57.7% in ER+ tumors and 25.7% in ER- tumors (p < 0.0001). Logistic regression analysis showed ER status, disease extent and pleural effusion as independent variables associated with CA 15-3 positivity. The multivariate Cox analysis showed ER and disease extent as independent variables predicting overall survival, whereas CA 15-3 failed to be statistically significant. CA 15-3 was an independent variable only when the disease extent variable was removed. This study suggests that CA 15-3 in advanced breast cancer patients is a marker of both disease extent and ER status. The direct relationship with ER status indicates that CA 15-3 diagnostic sensitivity in the early detection of disease recurrence could be greater in ER+ patients than in ER- ones. Furthermore, this suggests that patients with elevated CA 15-3 levels could have disease that is more sensitive to hormone manipulation than those with normal CA 15-3 values.

Adult↗
PubMedDate not supplied

Sentinel lymph node and breast cancer staging: final results of the Turin Multicenter Study.

AIM OF THE STUDY: Validation of the sentinel node (SN) technique in breast cancer by means of lymphoscintigraphy. MATERIALS AND METHODS: From December 1996 to January 1999 102 T1-T2 breast carcinoma cases were recruited in Turin. 99mTc-human serum albumin colloids were injected subdermally the day before surgery (mean activity, 5.2 +/- 2.5 MBq). Scintigraphic imaging was performed after injection. After identification of the SN during surgery by a hand-held gamma probe, the SN was excised and sent for histologic examination. SN histology was compared with that of other axillary nodes. RESULTS: The SN detection rate was 86.3%; among 88 cases with an identified SN, 37 (42%) had axillary metastases; the SN was metastatic in 35 cases (sensitivity, 94.6%); in 51.3% of pN+ cases (19/37) the SN was the only metastatic site. In two of the 53 negative SNs, SN histology did not match with that of the remaining axilla (negative predictive value, 96.2%; staging accuracy, 97.7%). CONCLUSIONS: Our results agree with those reported in the literature; however, except in clinical trials and experienced structures axillary lymph node dissection should not be abandoned when mandatory for prognostic purposes, considering that at present SN biopsy alone is not completely accurate for axillary staging, especially in the absence of an adequate learning period.

Adult↗
PubMedDate not supplied

Epidoxorubicin and paclitaxel as primary chemotherapy for T > 3 cm and T4 breast cancer patients.

UNLABELLED: The Anthracyclines/Taxanes combination is often used in adjuvant and advanced breast cancer. PURPOSE: To evaluate the toxicity and pathological response of sequential epidoxorubicin/paclitaxel combination as primary chemotherapy for T > 3 cm and T4 breast cancer patients. PATIENTS AND METHODS: Forty-eight patients with T2 > 3 cm, T3 and T4 breast tumours were treated with Epidoxorubicin (90 mg/m2, i.v.) on day one and paclitaxel (200 mg/m2 over 3 hours) on day 2 every 21 days for four courses. After the fourth cycle the patients underwent modified radical mastectomy or quadrantectomy plus axillary lymph node dissection followed by six courses of intravenous CMF regimen (days 1 and 8, every 4 weeks). Radiotherapy was given to patients undergoing conservative surgery or with T4 cancers. Tamoxifen was administered in ER or PgR positive patients. RESULTS: Out of the 48 patients enrolled into this trial, 43 were evaluable for toxicity and pathological response. Primary chemotherapy with epidoxorubicin and paclitaxel was well tolerated: no heart toxicity was observed during primary chemotherapy and follow-up. Primary toxicity consisted of myalgia, grade 1 neuropathy and grade 3 alopecia. Disappearance of invasive tumours in the breast with node negative was observed in 11.6% of patients: pathological partial response was shown in 56% of patients. On the whole major pathological response was achieved in 67% of our series: in the remaining 33% we found a stable disease or a size reduction less than 50%. No progressive disease was observed. Conservative surgery was performed in 64.5% of T2 and T3 tumours. CONCLUSION: These preliminary data showed that the epidoxorubicin/paclitaxel combination was safe and effective as primary chemotherapy for patients with T > 3 cm and T4 breast cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗