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Biomedical subjects

G Porzio

Publications and source records attributed to G Porzio.

At least 19 recordsLinked to original sources

From adjuvant to preventive breast cancer treatment: bridging the gap over troubled waters.

Recently, chemoprevention trials have demonstrated the efficacy of preventive medical treatment (PMT) in reducing breast cancer (BC) detection rates in at-risk affected and unaffected women selected according to clinical and/or familial risk criteria, particularly with the use of tamoxifen (TAM). Major concerns limiting the routine use of TAM are the questionable benefit/risk ratio and poor patient compliance, which justify the studies undertaken to determine the efficacy of aromatase inhibitors (AIs) with respect to TAM. Issues such as therapy duration, impact on survival, incidence of side-effects and which subsets benefit most from treatment, still remain unsolved. Therefore, only ER+ BC patients are routinely subjected to PMT, independently of their BRCA1/2 status, using adjuvant hormonal therapy. More attention must be focused towards BRCA1/2 carriers as they are probably the women at highest risk of developing BC, in which available data remain controversial and in which hormone-therapy might be important. Hence, at-risk women (affected patients or unaffected women) should be carefully evaluated for inclusion into highly selected preventive clinical trials aimed at evaluating PMT independently of, or according to, BC predisposition status (unknown, positive or negative BRCA1/BRCA2 status) and with respect to menopausal status. BC patients, harboring a BRCA1/2 predisposition, may represent the best subset for extended adjuvant treatment, useful as PMT, simultaneously. Only the evolving differentiation of categories of at-risk women will allow physicians to discriminate PMT in a highly selective manner.

Breast Neoplasms↗

Increased tolerability of bimonthly 12-hour timed flat infusion 5-fluorouracil/irinotecan regimen in advanced colorectal cancer: A dose-finding study.

A dose-finding study was designed to determine the maximum tolerated dose (MTD) of a bimonthly 12-h (10:00 p.m to 10:00 a.m), timed flat infusion (TFI) of 5-fluorouracil (5-FU) plus irinotecan (CPT-11), without leucovorin (LV), for metastatic colorectal carcinoma (CRC). A total of 33 patients were treated. Seven dose levels included a fixed CPT-11 dose of 180 mg/m2 on days 1 and 15 (d(1,15)) and escalating doses of 5-FU 600-1200 mg/m2 on days 1-4 and 15-18 (d(1-4,15-18)). Dose-limiting toxicities (DLTs) were: grade 3-4 non-hematologic, grade 4 hematologic and any toxicity causing a more than a 2-week delay in treatment. The MTD was reached at the seventh dose level. DLTs were observed in 5/8 patients (63%): G3 diarrhea, 2 patients, associated with G3 mucositis in one instance; G4 neutropenia, 2 patients, associated with severe asthenia in 1 patient; G3 hand-foot syndrome, 1 patient. The recommended doses (RDs) were established at the sixth dose level: 5-FU, 1100 mg/m2/d(1-4,15-18); CPT-11 180 mg/m2/d(1,15) [5-FU and CPT-11 dose intensity (DI), 2200 and 90 mg/m2 per week (w), respectively]. At the recommended dose, the DLTs in 38 cycles were: mucositis, 2 cycles (5%); afebrile G4 neutropenia and hand-foot syndrome, 1 cycle (3%). In 24 assessable patients, the overall response rate was 37.5%. The present CPT-11/5-FU schedule is highly tolerable in an outpatient setting using the highest recommended 5-FU dose effective in advanced CRC.

Adolescent↗

Timed flat infusion of 5-fluorouracil increases the tolerability of 5-fluorouracil/docetaxel regimen in metastatic breast cancer: a dose-finding study.

A dose-finding study was undertaken to determine the maximum-tolerated dose, and the recommended dose of docetaxel in combination with 12-h timed (22:00-10:00) flat infusion of 5-fluorouracil (5-FU) in metastatic breast cancer patients. This schedule seems to reduce the occurrence of stomatitis of the docetaxel and infusional 5-FU regimen.

Adult↗

Reducing breast cancer incidence in familial breast cancer: overlooking the present panorama.

Familial breast cancer, whether associated or not with particular other breast cancer features (male, early onset, bilateral breast cancer), determines a wide and variable risk of developing breast cancer in the 'unpatients' (unaffected individuals) of these families, particularly in those harboring a genetic predisposition. The antiestrogen tamoxifen has been proposed in different trials to prevent breast cancer in women at risk. The NSABP-P1 study demonstrated that tamoxifen drastically reduced (by approximately 50%) the incidence of breast cancer in women at risk selected according to the Gail score. The preventive effect was particularly consistent in postmenopausal women and in those showing familial breast cancer (three or more affected patients). BRCA1/BRCA2 (BRCA1/2) gene analysis in women accrued in the NSABP-P1 trial who developed breast cancer showed that tamoxifen chemoprevention reduced breast cancer incidence in BRCA2 carriers. Different chemoprevention trials are ongoing to compare different selective estrogen receptor modulators and aromatase inhibitors with tamoxifen. The Italian Consortium of Hereditary Breast Ovarian Cancer recently developed the Aromasin Prevention Study, a multicenter, double-blind, randomized, placebo-controlled phase III study evaluating the effect of the aromatase inhibitor exemestane for chemoprevention in postmenopausal women carriers of BRCA1/2 genetic predisposition. Women who are postmenopausal unaffected carriers of BRCA1/2 mutations will be selected by participating institutions and randomly assigned to receive either oral exemestane or oral placebo every day for 3 years in order to reduce the incidence of breast cancer. Genetic counseling and the detection of predisposing BRCA1/2 mutations are mandatory before accrual into the study. Signed informed consents for the performing of BRCA1 and BRCA2 genetic analysis and for enrollment into the study are required. Eligible women will be followed thereafter in order to evaluate the efficacy of exemestane in reducing the incidental rate of breast cancer in unaffected postmenopausal carriers of BRCA1/2 mutations.

Anticarcinogenic Agents↗

Prophylactic options in patients with 5-fluorouracil-associated cardiotoxicity.

At present, the various mechanisms involved in 5-fluorouracil (5-FU)-correlated cardiotoxicity remain to be elucidated and a universally accepted prophylaxis or treatment for this specific toxicity is not available. Although it may improve time to progression, survival and clinical benefit, a 5-FU-based regimen usually has to be discontinued if a patient experiences cardiotoxicity. Here, we describe our experience with three cases of 5-FU-associated cardiotoxicity. The angina-like pain that appeared approximately 95 h after beginning 5-FU therapy was apparently independent of the drug's administration modality. In the two patients receiving 5-FU 12-h flat continuous infusion from 22.00 to 10.00 h (5-FU 12-h c.i.) in combination with other drugs, the dose of 5-FU was reduced by 10-20% and patients received prophylactic transepidermal nitroglycerin. In the third patient, 5-FU administration modality was changed and prophylactic therapy was not given. By taking these precautions, the patients no longer complained of anginal pain and none of them discontinued chemotherapy.

Aged↗

Prognostic value of p53 molecular status in high-risk primary breast cancer.

BACKGROUND: Mutations in the p53 gene are the most common genetic alterations in human primary breast carcinoma and these mutations are often associated with worse prognosis and chemo/radioresistance. PATIENTS AND METHODS: The analysis of the p53 gene was performed by fluorescence-assisted mismatch analysis in 13 consecutive high-risk primary breast cancer (HR-BC) patients with 10 or more involved axillary nodes to evaluate its prognostic value. RESULTS: Three p53 mutations (23%) and four allelic variants were detected. After a median follow-up of 52 months the HR-BC disease-free survival (DFS) was 51% and overall survival 79%. All patients harboring a p53 mutation (p53(mut)) relapsed within 10 months of the median DFS while 67% of those showing a wild-type p53 status (p53(wt)) survive disease-free at a median follow-up of 43 months. One p53(mut) patient is still alive while all the p53(wt) patients survive at 56 months median follow-up. Two out of the four p53(wt) relapsing breast cancer patients showed the Arg72Pro allelic variant; one of these died at 75 months. CONCLUSIONS: p53 mutations may help identify a subset of very high risk breast cancer patients (vHR-BC) with worse prognosis.

Breast Neoplasms↗

Pelvic relapses in ovarian cancer. Role of CA-125, transvaginal ultrasound and color Doppler.

From January 1995 to January 2001, 40 patients with epithelial ovarian cancer were treated at our Institution. Fourteen of these, with a clinical CR after surgery and platinum-based chemotherapy, were evaluated monthly by gynecological examination, Ca-125 RIA assay, pelvic ultrasound with transabdominal and transvaginal probe and color Doppler. Six pelvic relapses, from 1.5 to 3.0 cm, were detected by transvaginal ultrasound (US). They showed a rich neovascularization with low resistance, high flow, PI from 0.3 to 1.0 and RI < 0.5 in all cases. US did not reveal any sign of relapse in the remaining eight patients. In all cases of pelvic relapses ultrasonic signs of recurrence preceded the increase of Ca-125 by one to six months (average 3.8).

Aged↗

Cerebral metastasis from ovarian cancer treated with a multidisciplinary approach. Case report and review of literature.

Brain metastases from ovarian cancer are rare. A review of five autopsy studies reported brain metastases in 4% of 712 patients who died with a diagnosis of ovarian cancer. The prognosis is very poor and a consensus on the standard treatment is not available. We report the case of a patient who developed a solitary brain metastasis as single evidence of relapse, 26 months after the first diagnosis of ovarian cancer. A temporo-parietal craniotomy with excision of the mass and whole brain radiotherapy were performed. The patient is free of disease five months after radiotherapy completion. Also in patients suffering from neoplasms that rarely metastasize to CNS, a careful clinical examination may help to diagnose uncommon sites of disease relapse.

Adult↗

Hypersensitivity reaction to carboplatin: successful resolution by replacement with cisplatin.

Hypersensitivity reactions caused by carboplatin rarely occur. These reactions can cause lethal complications and make subsequent therapeutic approaches difficult. To date, only a few cases of successful resolution of hypersensitivity by replacement of carboplatin with cisplatin have been reported. We report on a patient with serous papillary extra-ovarian peritoneal carcinoma who developed a hypersensitivity reaction after the 10th weekly administration of carboplatin. Two weeks after reaction, intradermal skin testing with paclitaxel, carboplatin, cisplatin, and mannitol showed intense reaction only to carboplatin. On the basis of these results, the patient was changed to a chemotherapy with cisplatin and paclitaxel. A further eight courses of chemotherapy were administered without evidence of hypersensitivity reactions. Carboplatin seems to be successfully replaceable by cisplatin in case of hypersensitivity reactions.

Aged↗

Surgical treatment of invasive carcinoma of the vulva. Our experience.

OBJECTIVE: The purpose of this study was to investigate the clinical findings, treatment and outcome of patients with vulvar carcinoma in the L'Aquila area. METHODS: Fifteen cases of vulvar carcinoma seen between September 1991 and December 1999 at the Department of Obstetrics and Gynecology of the University of L'Aquila were reviewed. Clinical, pathologic, surgical and follow-up data were collected from patient records. Mean age at diagnosis was 66.4 years. All patients were evaluated through a careful medical history and physical examination, vulvoscopy, abdomino-pelvic CT or MR, urethrocystoscopy, rectocolonscopy and SCC, and CEA determination. Radical surgery included six patients treated by the Taussig-Way operation. Modified radical surgery accounted for nine patients treated by the Byron three-incision approach. RESULTS: The major early complication was groin wound breakdown which occurred in four cases. The major late complication was chronic leg edema which was reported in six patients. The average number of nodes removed per patient was 19.5. Seven patients (46.7%) had a T2N0M0 pathologic stage, four (26.7%) were T2N1M0, four (26.7%) T1N0M0. Five patients died of local and distant recurrences within 37 months after surgical treatment; ten patients are alive, nine are apparently free from disease whereas one presented local and systemic recurrence within 18 months after surgery. CONCLUSIONS: Vulvar carcinoma predominantly affects older women. Most patients in our series (11/15) had tumors more than 2 cm in diameter. Although the vulva is an external organ and early detection should be achieved, many patients presented with extensive primary lesions due to both patient and physician delay. Stage of disease, tumor size, and nodal metastases are potential prognostic factors useful in selecting patients for a more conservative surgical approach.

Aged↗

[Hormone substitution therapy during menopause. Increase of compliance].

BACKGROUND: Hormonal replacement therapy (HRT) is always of major employ in the practice. Unfortunately, a high percentage of women interrupt therapy after a few months. METHODS: Two hundred menopausal women with intact uterus were studied. During the first consultation, they received an informative booklet regarding the menopause, without any verbal information. During the second visit, the gynaecologist discussed with the patient the information acquired and prescribed the HRT (50 mcg/die of transdermal estradiol, as continuous therapy, and 5 mg medroxyprogesterone acetate/os for 10 days/months) to those who required it. The compliance to treatment at 3, 6 and 12 months has been recorded. RESULTS: Of the 200 women studied, 153 referred to have read the informative booklet: 112 requested further informations to their family doctor; 97 discussed the contents with the partner; 130 expected HRT. The 3 months, 6 months and 12 months compliance has been of 110 (84%), 97 (74%) and 68 women (52%) respectively. Causes of drop out: breast tension (12%); water retention and/or increase of weight (20%); headache (7%); vaginal blood loss (22%); others [fear of cancer, etc.] (54%). CONCLUSIONS: According to personal opinion, three factors may condition the compliance to the HRT: 1) circumstantial information, not only verbal before the onset of therapy; 2) treatment protocols with low incidence of side effects; 3) frequent follow-up.

Adult↗

[Malignant gynecologic neoplasms during menopause. Authors' experience].

From January 1991 to December 1993 409 post-menopausal women were observed at the Center for the Study of Climateric Disorders of the Department of Obstetrics and Gynecology of the University of L'Aquila. The aim of the study was to evaluate the incidence of gynecologic neoplasm among this group of women. A total of 48 women at risk for malignant tumors were detected. The relationship between the climateric age and the oncologic risk is discussed.

Adult↗

[Synchronous associations of tumors in the pelvic organs of the female genital tract].

The Authors report their findings concerning the synchronous associations of tumours involving pelvic organs in the female genital tract observed at the Gynecological Clinic, Aquila. From January 1980 to December 1991, 9 cases (4.28%) of synchronous tumours were found in a total of 210 cases of womb, ovary and vagina tumours. The paper examines the clinical problems and questions of anatomopathological characterisation raised by these associations.

Endometrial Neoplasms↗

[Cervical maturation. Physiologic aspects and pharmacologic implications].

The latest theories on cervical maturation and the techniques of pharmacological induction of labour are summarised. The role of the prostaglandins is particularly stressed both from the physiological viewpoint and as drugs of choice for effective pharmacological induction of uterine cervix. Finally, the personal clinical protocol for the induction and management of labour is reviewed.

Adult↗