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Biomedical subjects

S Pecorelli

Publications and source records attributed to S Pecorelli.

126 records · Page 7Linked to original sources

Cisplatin, vinblastine, and bleomycin combination chemotherapy in metastatic granulosa cell tumor of the ovary.

Eleven previously untreated women with recurrent and/or metastatic granulosa cell tumor of the ovary were treated with cisplatin, vinblastine, and bleomycin in combination. All the six pathological complete responders but one are alive and free of disease at a median follow-up time of 14 months from the start of treatment. Of three partial responders, two died of drug-related toxicity while one, with only microscopic disease at second-look laparotomy, is alive and without evidence of disease at 34 months. Hematologic and nonhematologic toxicity were severe. These promising results require further examination of the activity and the best schedule of treatment with this combination.

Adult↗

Management of gestational trophoblastic disease: results of a cooperative study.

Three hundred fifty-four evaluable cases of hydatidiform mole diagnosed from 1970 to 1979 in 10 regional hospitals in Lombardy are analyzed in the present report. Twenty-six (7.3%) of the patients developed persistent trophoblastic disease. Younger (less than 20 years) and older (40 years or more) age at diagnosis, a large-for-dates uterus, and ovarian enlargement were associated with an increased risk of developing persistent trophoblastic disease. Twenty-three (9%) cases of persistent trophoblastic disease were observed among 250 women not prophylactically treated, but only in 3 (3%) among 104 who received prophylactic chemotherapy. High-risk groups are defined and the role of prophylactic chemotherapy is discussed.

Adolescent↗

[Human chorionic somatommamotropins (HCS or HPL) : radioimmunologic determination and clinical significance].

The AA. have studied a new standardized radioimmunologic method for the routine determination of HCS. All the steps of the analysis have been studied, in particular those concerning the reability test and the precipitation of the complex with PEG. The best conditions were found when PEG 6000 is used at a concentration between 14-16 g in 100 ml (v/w), dissolved in veronal buffer, pH 7.4--9.4, with a dilution of protein (bovine serum) 1:4 in the incubation mixture. The reability test have given very good results. The c.p.m. of the analysis are plotted with a logit plot by computer which directly gives the values in ng/ml of the hormone in the plasma sample. The results obtained with this method are compared with those of the literature; the most striking difference in the present method appears in the last trimester of pregnancy in which the result have a low S.D. and can give a good help in clinical management of pregnant patients.

Abortion, Threatened↗

Gynecological sarcomas.

Sarcomas of the uterus, ovary and lower genital tract are fortunately rare, since the prognosis is quite often poor. The most frequent are sarcomas of the uterine corpus, and these account for only 4% of all uterine tumors. Ovarian sarcomas are less frequent, and the prognosis is even poorer when compared to the uterus. Sarcoma of the lower genital tract (vagina and vulva) in adults is often published as a case report, given their very infrequent occurrence.

Endometrial Neoplasms↗

Restoration of tumor specific human leukocyte antigens class I-restricted cytotoxicity by dendritic cell stimulation of tumor infiltrating lymphocytes in patients with advanced ovarian cancer.

Despite the large number of potentially cytotoxic tumor-infiltrating (TIL) and tumor-associated (TAL) lymphocytes accumulated in the peritoneal cavity ascitic fluid and tumor tissue, advanced ovarian cancer is a progressive disease, suggesting that TIL and TAL populations eventually become functionally suppressed in vivo. Dendritic cells (DC) are the most powerful professional antigen presenting cells known in humans and recently, ovarian tumor antigen pulsed DC have been shown to elicit tumor specific human leukocyte antigens (HLA)-class I-restricted cytotoxicity from the peripheral blood of advanced ovarian cancer patients. In this study, we have evaluated the potential of tumor antigen-pulsed fully mature DC stimulation in restoring tumor-specific cytotoxicity in anergic TIL populations from advanced ovarian cancer patients. In addition, we have compared tumor-specific T-cell responses induced by tumor antigen-loaded DC in TIL to those induced in TAL and peripheral blood lymphocytes (PBL). DC stimulation induced powerful cytotoxicity against autologous tumor target cells in TIL-derived CD8+ T-cells from all patients tested, while autologous Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCL) were not lysed. Killing of autologous tumor cells was higher by CD8+ T-cells from TIL compared to PBL and TAL (P < 0.01) and was more strongly inhibited by anti-HLA class I MAb (P < 0.05 compared to PBL and TAL). Phenotypically, all cytotoxic T lymphocyte (CTL) populations were CD3+/CD8+, with variable levels of CD56 expression. Finally, although a marked Type 1 cytokine bias [ie, interferon-gamma/interleukin-4 (IFN-gammahigh/IL-4low)] was observable in all DC-stimulated CD8+ T-cell populations, TIL derived CD8+ T-cells showed a higher percentage of IFN-gamma positive cells compared to TAL and PBL. Taken together, these data show that tumor lysate-pulsed DC can consistently restore strong CD8+ CTL responses from TIL against autologous ovarian cancer cells. DC-stimulated TIL may represent a superior source of tumor-specific CTL for adoptive T-cell immunotherapy for advanced ovarian cancer.

Aged↗

Long-term follow-up confirms a survival advantage of the paclitaxel-cisplatin regimen over the cyclophosphamide-cisplatin combination in advanced ovarian cancer.

Two independent and consecutive randomized clinical trials, conducted by the American Gynecological Oncology Group and by an European-Canadian Intergroup, have shown superiority, in clinical response rate, progression-free survival, and overall survival, of a cisplatin-paclitaxel regimen over cisplatin-cyclophosphamide given as first-line chemotherapy for women with advanced epithelial ovarian cancer. The results of these studies, published with a median follow-up of about 3 years, have been updated with a 6.5-year follow-up: In each case, an 11% absolute gain in survival favoring the paclitaxel arm is shown; this advantage remains both statistically and clinically significant and supports a role for paclitaxel in frontline chemotherapy for advanced ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Consolidation therapies revisited: weekly paclitaxel.

Most patients with advanced ovarian cancer exhibit clinically relevant objective and subjective responses to platinum/paclitaxel-based combination, which is now considered the standard chemotherapeutic regimen. Unfortunately, responses are generally of limited duration, and long-term disease-free survival is experienced by few patients. Efforts should be taken to maintain such a response as long as possible, where it realistically might be hoped that continuation of chemotherapy could consolidate the absence of clinically detectable disease. In this regard, the administration of paclitaxel on a weekly schedule seems to be particularly attractive, especially after the demonstration that a weekly regimen in heavily pretreated women bearing metastatic breast, head, and neck or lung cancers was proven to be well tolerated without the requirement of granulocyte colony-stimulating factors, with limited neurotoxicity and with substantial anticancer activity, thanks to its pro-apoptotic and antiangiogenesis properties. In Italy, a multi-institutional phase II prospective study (After-6 Protocol 2) has been initiated to verify the effectiveness of paclitaxel, administered on a weekly schedule (60 mg/m2 for 21 courses), in patients bearing microscopic residual disease detected at second-look operation to define its effectiveness after completing their primary platinum/paclitaxel chemotherapy treatment. When possible, patients were surgically re-evaluated thorough a third-look operation to evaluate the percentage of conversion of microPR into a pathological complete remission status. An interim evaluation based on 534 cycles administered to 41 patients showed than only one patient experienced grade 4 anemia, 7.4% grade 2 transient peripheral neurotoxicity, and 2.7% delay in treatment delivery. Therefore, weekly paclitaxel has been proven to be easily administered even in heavily pretreated patients, with acceptable hematological and neurological toxicity.

Antineoplastic Agents↗

What have we learned from ICON1 and ACTION?

Still, 20-30% of women with early-stage ovarian cancer eventually die from their disease. Adequate treatment for this subset of patients has not yet been identified, the greatest dispute being about the role of adjuvant therapy after surgical staging. No randomized trial has reliably demonstrated a survival advantage for one of the many approaches over another or over careful observation without immediate further adjuvant therapy. A combined analysis of two parallel randomized clinical trials in early ovarian cancer, ICON 1 and ACTION, comparing platinum-containing adjuvant chemotherapy to observation following surgery was performed, with survival as primary end point and time to recurrence as a secondary one. A total of 924 patients were randomized. With over 4 years median follow up for survivors, the hazard ratio for recurrence-free survival is 0.64 (95% CI, 0.50-0.82; P = 0.001) in favor of adjuvant chemotherapy, with an absolute difference of 11%. For overall survival, the hazard ratio is 0.67 (95% CI, 0.50-0.90; P = 0.008) in favor of adjuvant chemotherapy. These results translate into an absolute difference of 8% in the adjuvant chemotherapy group and indicate that adjuvant platinum-containing chemotherapy improves the survival and disease-free survival. Sub-group analysis demonstrated in the ACTION trial that completeness of surgical staging was an independent factor for prognosis, both for progression-free and for overall survival (along with histological type and tumor grade), while in suboptimally staged patients, adjuvant chemotherapy did improve the outcome.

Chemotherapy, Adjuvant↗

Surgery of advanced malignant epithelial tumours of the ovary.

Surgery is still the cornerstone in the management of advanced epithelial ovarian cancer (AEOC) patients. It involves: i. establishment of diagnosis and staging; ii. primary cytoreduction; iii. interval cytoreduction, interval debulking surgery (IDS) or surgery after neoadjuvant chemotherapy; iv. secondary cytoreduction during the assessment of the status of the disease at the end of primary chemotherapy - second look; v. surgery for recurrence; vi. palliation. Substantial evidence exists to demonstrate that if surgery is performed by gynaecologists with a special training in gynaecological oncology, a survival advantage can be achieved when compared with that obtained when general surgeons are primarily treating AEOC. Primary surgery with diagnostic and cytoreductive intent should be performed in accordance with the European Guidelines of Staging in Ovarian Cancer. Whether or not cytoreduction should systematically include lymphadenectomy is still a controversial issue. The strong correlation between chemosensitivity, successful debulking surgery and survival strongly support the concept that it is the biological characteristic of the disease rather than the aggressiveness of the surgeon to allow a successful cytoreduction to the real optimal disease status. It should be now recognised as the complete absence of disease at the end of the surgical procedure. Both IDS and neoadjuvant chemotherapy represent a strong effort to achieve such a status through less morbidity and a better quality of life for the patient. Surgery for recurrence and palliation need to be optimised both in terms of patient selection and a better integration with chemotherapy and ancillary management.

Carcinoma↗