Biomedical subjects

S Chiara

Publications and source records attributed to S Chiara.

At least 37 records · Page 2Linked to original sources

PubMed1992

Cisplatin-based combination chemotherapy with or without doxorubicin in advanced epithelial ovarian cancer: 8-year update of a randomized multicentric clinical trial. The Gruppo Oncologico Nord Ovest (GONO).

One hundred and twenty-five patients with advanced epithelial ovarian cancer (EOC) were postsurgically included in a multicentric clinical trial comparing the association of cisplatin (CDDP) (50 mg/m2 iv day1) + cyclophosphamide (CTX) (600 mg/m2 iv day 1) (PC regimen) versus the combination of PC + doxorubicin (ADM) (45 mg/m2 iv day 1) (PAC regimen), repeated every four weeks. After the sixth course of chemotherapy, patients without clinical evidence of disease or with surgically resectable residual disease (RD) underwent second-look laparotomy. Afterwards patients in surgical complete response (sCR) stopped chemotherapy, while partial responders or patients with stable disease received six more courses of the same regimen used as first-line treatment. Among the 67 patients with measurable RD, PAC regimen achieved a better clinical complete response (40.6% vs 20.0%); the difference approached statistical significance. In the 75 patients who underwent second-look laparotomy, PAC regimen induced a significantly higher sCR rate (62.2% vs 39.5%, p less than 0.05). The median survival (S) and progression free survival (PFS) were better in PAC arm, even if the differences were not statistically significant. Eight-year S and 8-year PFS were 32.7% and 24.7% respectively, for PAC arm, and 23.9% and 14.1%, respectively, for PC arm. These data seem to confirm the clinical advantage provided by the addition of ADM to PC regimen in the treatment of advanced EOC.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1991

Effect of recombinant human tumor necrosis factor on A2774 human ovarian cancer cell line: potentiation of mitoxantrone cytotoxicity.

Recombinant human tumor necrosis factor (rHuTNF) is a macrophage-secretory protein with antitumor activity. In vivo and in vitro cytotoxicity studies have been carried out to test the effectiveness of rHuTNF alone or in combination with chemotherapeutic agents. We have evaluated the direct cytotoxic effect of rHuTNF on a human epithelial ovarian cancer cell line in vitro (A2774), alone, or in combination with mitoxantrone (Mit), a topoisomerase II (Topo II) targeted drug. Our results not only suggest that rHuTNF is directly cytotoxic, but also that it is able to induce a very strong potentiation of Mit cytotoxicity.

Dose-Response Relationship, Drug↗

PubMed1991

Adjuvant cisplatin-based chemotherapy for stage I and II ovarian cancer: a 7-year experience.

87 patients with high risk of recurrence FIGO stage I and II ovarian carcinoma were treated with adjuvant chemotherapy consisting of cisplatin 50 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 every 28 days for 6 courses. Toxicity and efficacy of the regimen was evaluated after a median follow-up of 45 months. Treatment-related toxicity was mild and reversible, consisting chiefly of acute WHO grade 2 myelosuppression (10% of patients) and controllable grade 3 emesis (55%). No late toxicity was observed. Actuarial 7-year survival and relapse-free survival (RFS) were 76% and 61%, respectively; a statistically significant difference in outcome was observed for undifferentiated grade tumour (G1 vs. G2 vs. G3: P less than 0.01) but not for FIGO stage disease (stage I vs. stage II). In our opinion, short-term chemotherapy including the most active single agent, i.e. cisplatin, appears a tolerable and effective treatment which deserves further evaluation in large randomised trials.

Adult↗

PubMed1991

Abdominopelvic radiotherapy following surgery and chemotherapy in advanced ovarian cancer.

Thirty advanced ovarian cancer patients have been treated with sequential multimodality treatment including primary surgery, cisplatin or carboplatin-based polichemotherapy, second-look laparotomy followed by abdominopelvic irradiation (moving strip or open-field technique). Toxicity related to the combined treatment was acceptable: only three patients failed to complete and two patients delayed the prescribed course of radiotherapy because of acute myelosuppression or gastroenteric disturbances. One patient without evidence of disease required laparotomy for bowel obstruction one month after completion of radiotherapy. No other chronic toxicity of clinical significance has been observed. Actuarial three-year survival significantly correlated with residual disease at the start of radiotherapy: no residuum, 100%, microscopic disease, 52%; less than 2 cm macroscopic disease, 27.4% (P less than 0.05), whereas recurrences were less frequent only in the group of pathological complete responders (3/9) compared to patients with limited disease (6/11 with micro and 7/10 with macroscopic residuum). In conclusion radiotherapy following surgery and chemotherapy is not associated to serious morbidity but its value in improving progression-free survival rates has to be tested in randomized trials.

Abdomen↗

PubMed1991

Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.

One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.

Adult↗

PubMed1990

Prognostic factors in stage IV ovarian carcinoma treated with platinum-based regimens.

Eight factors were analyzed for prognostic significance in univariate analyses in a series of 76 women with stage IV ovarian carcinoma treated with combination chemotherapies including cisplatin or carboplatin. The clinical objective and pathologic complete response rates were 51.2% and 27.3%, respectively. Median overall survival and progression-free survival were 15 and 7 months, respectively. No variables reached statistical significance. Trends toward better survival were noted for grades 1 and 2 for the adriamycin-containing regimen. Using progression-free survival as an end point, significant prognostic factors included complete clinical or pathologic response. Our data confirm that the standard approach is unlikely to modify the clinical outcome of stage IV ovarian cancer. New treatment modalities including high-dose-intensity regimens and neo-adjuvant chemotherapy delivered before surgery could improve clinical results. Moreover, biologic characterization of ovarian tumors may provide information to design specifically targeted treatment.

Adult↗

PubMed1990

Chemotherapy versus radiotherapy in the management of ovarian cancer patients with pathological complete response or minimal residual disease at second look.

The management of patients with epithelial ovarian cancer with no or minimal residual disease at second-look laparotomy after aggressive surgery and platinum-based chemotherapy has not been definitively established. We report the results of a randomized study comparing three more courses of the same chemotherapy inducing the response (21 patients) with whole-abdomen radiotherapy (20 patients). Thirty-eight patients responded to first-line chemotherapy and three had stabilization of disease. In eight patients tumor debulking was performed at second-look laparotomy. No severe toxic effects were noted in both arms. Bowel obstruction occurred in one patient treated with radiotherapy. At a median follow-up of 22 months, 11 of 20 patients in the radiotherapy arm and 6 of 21 in the chemotherapy arm progressed and 9 and 3 patients died, respectively. Although the number of randomized patients is small we stopped the trial because of the survival and progression-free survival advantage of chemotherapy-treated patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

Intraperitoneal cytosine arabinoside administered in sequence with systemic cisplatin, doxorubicin, and cyclophosphamide in advanced ovarian cancer.

After standard management of stage III-IV ovarian cancer patients by surgical reduction of tumor mass and subsequent cisplatin-based combination chemotherapy, eradication of residual intraabdominal disease remains a major clinical problem. In an effort to increase response to therapy without adding marrow toxicity, after laparotomy, 21 stage III-IV ovarian cancer patients were treated with systemic chemotherapy comprising cisplatin, doxorubicin, and cyclophosphamide (PAC) on Day 1 followed by intraperitoneal (ip) cytosine arabinoside (Ara-C) on either Day 8 or 14, every 28 days. Ara-C, an S-phase-specific drug, was administered ip to exploit the pharmacologic advantage of an ip regimen at a time when a possible PAC-induced recruitment of cells into the proliferative pool could further maximize cell kill. Kinetic features of ovarian neoplastic cells recovered from peritoneal washings were monitored during treatment by measurement of the thymidine labeling index (TLI): data from four patients indicate that there is an increase in proliferating cells on Days 8 and 14 after PAC treatment. Toxicity of treatment was acceptable. Although 95% of evaluable patients had more than 2 cm of residual disease, response was observed in 47% of patients. The therapeutic potential of this regimen should be tested in patients with small-volume disease after debulking surgery.

Aged↗

PubMed1990

Crossover study with cisplatin or carboplatin in advanced ovarian cancer.

Fifty-seven patients who had progressed during or relapsed after randomized first-line combination chemotherapy containing cisplatin or carboplatin were entered into a crossover study in which the analog not previously assigned was administered alone as salvage treatment. Carboplatin and cisplatin were administered at doses of 400 and 100 mg/m2, respectively, every 28 days. Among the 24 patients enrolled in the cisplatin arm, 6 (25%) objective responses (ORs) (3 complete, 3 partial) were observed, whereas 3 partial responses were obtained in the 33 carboplatin-treated patient (9%). Analysis of results, according to response to first-line chemotherapy, demonstrated that the patients who progressed were sensitive only to cisplatin second-line treatment (OR: 3/12), with no responders among carboplatin-treated patients (OR: 0/11). All patients were treated on an outpatient basis and therapy-related toxic effects were mild, consisting chiefly of myelosuppression, and more frequent in the carboplatin group. In our opinion, carboplatin 400 mg/m2 per cycle is scarcely effective in patients with refractory or relapsed ovarian cancer pretreated with cisplatin regimens, whereas cisplatin 100 mg/m2 per cycle appears to be an effective salvage therapy even in patients not responding to carboplatin. The dose of carboplatin should be further escalated especially in refractory patients.

Carboplatin↗

PubMed1990

Double-blind randomized trial of lorazepam versus placebo with methylprednisolone for control of emesis due to non-cisplatin containing chemotherapy.

Fifty-three breast cancer patients receiving adjuvant chemotherapy entered a double-blind randomized trial of lorazepam 2.5 mg orally prior to chemotherapy and repeated after 12 hours (Arm A) versus placebo (Arm B) with methylprednisolone (MPN) 375 mg in 3 equal doses: 125 mg i.v. prior to chemotherapy and repeated i.m. 6 and 12 hours later. Adjuvant therapy with 5-fluorouracil 600 mg/m2, 4'-epi-doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2 (FEC) day 1 was alternated every 21 days with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, 5-fluorouracil 600 mg/m2 (CMF) day 1 for a total of 12 courses. The majority of patients experienced greater than or equal to 5 emetic episodes with FEC therapy (Arm A = 52%; Arm B = 55%). Mild and moderate nausea were reported by 60% and 68% of patients in Arms A and B, respectively. With CMF therapy complete control of emesis was observed in 33% (Arm A) and 35% (Arm B) of patients. The addition of lorazepam did not improve results either with FEC or CMF. Sedation was experienced by 86 to 92% of patients treated with lorazepam and amnesia was observed in 48-50% of cases. FEC therapy must be considered a highly emetic regimen and antiemetic therapy planned accordingly.

Adult↗

PubMed1990

Effect of recombinant human TNF on human ovarian cancer cell lines.

Ovarian cancer is the second most common gynecologic malignancy. Standard therapeutic approaches to this disease, surgery followed by chemotherapy, have produced response rates of up to 80%. However, the five-year survival rate remains around 30%. Recently, Tumor Necrosis Factor (TNF) has received attention as either an alternative or an associated agent for chemotherapy of ovarian cancer. TNF is known to have direct cytotoxic and cytostatic effects on a variety of transformed cell lines "in vitro". Furthermore, TNF is known to enhance significantly the "in vitro" effects of a class of chemotherapeutic agents, specifically those targeted at DNA topoisomerase II. In this work we have investigated TNF-induced cytotoxicity in four established human epithelial ovarian cancer cell lines: A-2774; SV-626; SKOV-3 and Pa-1. TNF mediated cytotoxic activity was observed in a range of concentrations between 1 U/ml and 10-3 U/ml. A-2774 and SV-626 were the two most sensitive lines, especially when exposed to high concentrations of TNF.

Cell Survival↗

PubMed1989

Cell kinetics in ovarian cancer. Relationship to clinicopathologic features, responsiveness to chemotherapy, and survival.

The tumor proliferative activity of 74 previously untreated epithelial ovarian carcinomas was evaluated by the thymidine labeling index (TLI) and the primer-dependent alpha DNA polymerase assay (PDP-LI). The median TLI and PDP-LI were 2% (0.1 to 28.0) and 10% (3.0 to 80.0), respectively. The TLI was significantly correlated to tumor grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and residual disease. However, neither the TLI nor the PDP-LI was a predictor of survival. A higher response rate was observed in the case of rapidly proliferating tumors: an objective response (OR) was observed in 38.4% of the patients with a low TLI and in 53.6% of the patients with a high TLI. The advantage of an OR in favor of the high TLI group was significant for patients treated with regimens containing doxorubicin (high TLI, 72.2% OR; low TLI, 40% OR; P = 0.03).

Aged↗

PubMed1989

Evaluation of the ovarian cancer antigen, Ca-125, as a tumor marker.

The presence of the Ca-125 antigen was tested in the serum of 46 patients with ovarian cancer in order to determine the prognostic value of preoperative levels and its usefulness for monitoring the clinical response in longitudinal studies; survival (S) and progression-free survival (PFS) were also evaluated. In our series, the specificity of the assay in normal subjects and in patients with benign gynecological diseases is 99.3 and 73.2% respectively, and the sensitivity is 91.9%. Preoperative Ca-125 levels are not correlated with S and PFS, whereas an advantage in S and PFS is clearly shown for patients in whom the marker level decreases after treatment. Serial determinations of Ca-125 serum levels provide a reliable test to assess response to therapy and to predict disease progression.

Antigens, Tumor-Associated, Carbohydrate↗

PubMed1988

Cisplatin and 5-fluorouracil in advanced and recurrent cervical cancer.

Nineteen consecutive patients with advanced or recurrent cervical cancer were treated with cisplatin 20 mg/m2 plus 5-fluorouracil 200 mg/m2 on days 1-5 every 3 weeks. Toxicity was acceptable and manageable, with most patients treated on an outpatient basis. The most important side effect was dose-cumulative neurotoxicity. In 18 evaluable patients a 61% objective response rate (1 complete and 10 partial) was achieved. In recurrent disease the regimen was effective both in irradiated lesions and in non-irradiated ones. Two out of five patients not previously treated with radiotherapy and/or chemotherapy responded to the treatment but tumor regression was insufficient for the disease to be controlled radically by subsequent surgery or radiotherapy. The median duration of response was 11 months (3-23) and the actuarial survival rate after 36 months follow-up was 43.3%.

Adult↗

PubMed1988

Carboplatin (JM 8), adriamycin and cyclophosphamide (JAC) in advanced ovarian carcinoma: a pilot study.

Eleven untreated patients with advanced ovarian cancer were studied for tolerance and response to combination treatment with fixed doses of adriamycin (45 mg/m2) and cyclophosphamide (600 mg/m2) + escalating doses of carboplatin. At the first dose level of carboplatin (200 mg/m2), toxicity was acceptable. With carboplatin at 300 mg/m2, severe hematologic toxicity was observed. The dose-limiting toxicity was leukopenia. Although carboplatin was administered without any hydration, no patient experienced renal toxicity. Eight objective responses were observed in 9 clinically evaluable patients. At second look surgery, 3 complete responses and 4 partial responses were documented. Polychemotherapy with JAC (carboplatin, 200 mg/m2, adriamycin, 45 mg/m2, and cyclophosphamide, 600 mg/m2) is administrable with acceptable toxicity.

Aged↗

PubMed1988

Moving-strip abdomino-pelvic radiotherapy after cis-platinum-based chemotherapy and second-look operation. A feasibility study in advanced ovarian cancer.

Sixteen FIGO stage IIB-IV ovarian carcinoma patients who completed six to 12 courses of a cisplatinum-based combination chemotherapy and with minimal (less than 2 cm), microscopic, or no residual disease at second-look laparatomy received moving-strip abdomino-pelvic radiotherapy. Radiation treatment was feasible with acceptable toxicity; two patients had to interrupt therapy--one pretreated with 12 PAC courses because of WHO grade III leukopenia and the other because of grade III diarrhea. A third patient required surgery because of intestinal obstruction 1 month after cessation of radiotherapy. In patients with minimal residual disease at second look, the therapeutic value of sequential radiotherapy was unsatisfactory (five of six progressed), while further investigations were warranted in patients with no or microscopic residuum after second-look operation.

Aged↗

PubMed1988

Uterine sarcomas: a clinicopathologic study.

A series of 48 cases with initial diagnosis of uterine sarcoma was reviewed to evaluate the validity of histologic criteria. The influence of pathologic and clinical prognostic factors and treatment modalities were examinated. The 32 patients included in this retrospective study after pathologic review had 5-year overall survival rate of 13.1%. Surgical pathological staging was demonstrated to be a significant prognostic factor, since patients with FIGO stage I-II disease had 33.5% actuarial survival rate whereas no patient with stage III-IV disease was alive at 37 months. Histological type, age and menopausal status did not significantly influence survival. Presence of heterologous elements and lymphovascular invasion were associated with a poor prognosis in the subgroup of patients with mixed mesodermal tumors. Median survival for patients receiving adjuvant treatment was 25 months compared to 19 months for those undergoing no adjuvant therapy.

Adolescent↗

PubMed1987

Methylprednisolone for the control of CMF-induced emesis.

Sixty-eight breast cancer patients for outpatient adjuvant chemotherapy (CT) with cyclophosphamide, methotrexate, and fluorouracil (CMF) on a 1-day schedule entered a randomized trial comparing the antiemetic-efficacy of different doses of methylprednisolone (MPN). Treatment was administered concomitantly with the first course of CT and consisted of MPN in either 375 or 120-mg doses divided into 3 equal parts, the first administered i.v. just prior to CMF and then i.m. 6 and 12 h after CT. Overall, antiemetic protection was appreciable: complete emetic protection (no emetic episodes) was observed in 71 and 66% of patients receiving MPN 375 and 120 mg, respectively. In 43 and 54% of patients receiving MPN 375 and 120 mg, respectively, nausea did not occur. Efficacy of the two treatment arms was not statistically different for either emesis or nausea. Antiemetic protection with MPN was reproducible over time at subsequent courses: 60% of patients in either treatment arm experienced less than 5 emetic episodes at their 12th CMF course. Facial flush was the most frequently observed side effect (36% with MPN 120 mg vs. 68% with MPN 375 mg). Other acute untoward effects consisted of headache, pyrosis, and edema. However, the latter was observed only with the higher dose. In patients receiving CMF, MPN alone provides effective and reproducible emetic protection. No dose-response relationship was observed.

Adult↗