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Biomedical subjects

M Bruzzone

Publications and source records attributed to M Bruzzone.

At least 37 records · Page 2Linked to original sources
PubMed1993

The impact of received dose intensity on the outcome of advanced ovarian cancer.

It has been demonstrated that the prognosis of ovarian cancer is influenced by the dose intensity of cytotoxic treatment. The impact of received dose intensity of platinum-based combination chemotherapy on disease outcome was analysed in 226 stage III-IV ovarian cancer patients entered into two prospective randomised trials. All patients received either cisplatin or carboplatin and cyclophosphamide with or without doxorubicin for six courses after primary surgery. The impact of the received dose intensity of each drug (RDI), the average received dose intensity of the treatment regimen (ARDI) and the relative total drug dose (RTD) on progression-free survival (PFS) and survival were analysed. In the 198 patients receiving the full six courses of treatment, RDI of cisplatin or carboplatin, ARDI and RTD were > 0.76 in 74.2, 61.1 and 65.1% of cases, respectively. Although the differences were not significant, pathological complete response was more frequently observed in the group of patients with ARDI < 0.75, whereas the partial response rate was higher in the ARDI > or = 0.76 group. Median survival and PFS were 19 and 13 months; 22 and 10 months; 23 and 13 months for the groups of patients receiving chemotherapy at a ARDI of < 0.75, > or = 0.76-0.99 and > 1.00, respectively (P = not significant). It appears that modest dose modifications and brief treatment delays during first-line platinum-based chemotherapy do not affect response rate, survival and PFS in advanced ovarian cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Cisplatin-based chemotherapy in recurrent or high risk ovarian granulosa-cell tumor patients.

Nine chemotherapy-naive women with recurrent (2 patients) or high risk factors (bilateral or extraovarian spread, poorly-differentiated tumor, age > or = 40 years at diagnosis, residual disease after surgery) granulosa-cell tumors were treated with cisplatin, cyclophosphamide with or without doxorubicin (PAC, PC) or cisplatin, etoposide and bleamycin (PVP-16B). Toxicity was acceptable and the most frequently encountered adverse reactions were WHO grade 3 gastrointestinal toxicity in 77% of patients, and grade 3 myelosuppression in 22% of cases. Clinical complete response was achieved in the 2 patients with recurrent disease. Five patients underwent second look surgery which documented: complete response in 3 patients, partial response in 1 patient and progressive disease in 1 case. Median survival was 85 months (range 14-103). Cisplatin-based cytotoxic regimens may be of benefit in the treatment of recurrent or high risk granulosa-cell tumors.

Adult↗
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

Cerebromeningeal pleomorphic xanthoastrocytoma. Report on four cases: clinical, radiologic and pathological features. (Including a case with malignant evolution).

Three cases of cerebromeningeal pleomorphic xanthoastrocytoma are presented and the recurrence of a fourth case, previously described in 1980, is examined because of its evolution towards malignancy. Clinical, radiologic and pathological aspects are discussed and the general features of the previously reported cases of xanthoastrocytoma are reviewed.

Adolescent↗
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

The incidence of narcotic-induced emesis.

Epidemiologic studies of the incidence of emesis induced by narcotic analgesics are lacking. The histories of 260 cancer patients receiving oral narcotic analgesics prescribed at the Pain Clinic of our Institute from December 1988 to December 1989 were reviewed. Of the 260 patients, 120 were women, median age 61 (range 30-90) yr and 140 were men, median age 62 (range 30-82) yr. Nausea and vomiting associated with assumption of the various narcotics were buprenorphine 8.3% and 22.7%, morphine 18.3% and 28%, codeine 16.2% and 29.7%, and oxycodone 10% and 40%, respectively. Since the use of narcotic analgesics can effectively relieve pain and improve quality of life in cancer patients, it is important to be aware of the incidence of narcotic-induced emesis in order to use appropriate prophylactic antiemetic therapy.

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

Renal ammoniagenesis in humans with chronic potassium depletion.

Renal ammonia production and distribution and ammonia precursor utilization were evaluated in eight patients with chronic potassium depletion (CPD) and aldosterone-producing adenoma and in 20 controls. In CPD, urinary ammonia excretion and ammonia added to renal venous blood were about twofold higher than in controls; thus, total ammonia production was significantly augmented (88.0 +/- 10.3 mumol/min.1.73 m2 vs. 45.0 +/- 2.6 in controls). Total ammonia production was inversely correlated with serum potassium and directly correlated with urine flow. Stepwise multiple regression analysis showed that both factors, mainly serum potassium, significantly influence ammonia production and account for 61.4% of variations in ammonia production. Renal extraction of glutamine was significantly increased (56.6 +/- 5.9 mumol/min.1.73 m2 vs. 34.6 +/- 3.1 in controls), and this could account for ammonia production. The ratio of urinary ammonia excretion to total ammonia production, an index of the intrarenal ammonia distribution, was similar in patients and controls, and was significantly correlated with urine pH and true renal blood flow (RBF). Stepwise multiple regression analysis showed that RBF, urine pH and urine flow also significantly affected ammonia distribution. However, these factors accounted for only 41.7% of variations in intrarenal ammonia partition, urine pH having a minor role. We conclude that in patients with CPD other factors besides urine pH, urine flow and RBF intervene in the ammonia partition between urine and blood.

Acid-Base Equilibrium↗
PubMed1991

Ifosfamide and etoposide salvage treatment in advanced ovarian cancer.

Twelve FIGO stage III-IV ovarian cancer patients progressing or relapsing after primary cisplatin-containing combination chemotherapy were treated with ifosfamide and etoposide. Only patients with clinically evaluable disease entered the trial. The 12 patients received a median number of 3 courses (range 1-6). No complete or partial response and two disease stabilizations were observed. Ten patients progressed on therapy. The combination of ifosfamide and etoposide does not appear to be an effective salvage treatment for advanced ovarian cancer.

Adult↗
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↗
PubMed1991

A phase I study of recombinant interleukin-2 intraperitoneal infusion in patients with neoplastic ascites: toxic effects and immunologic results.

A phase I study to evaluate the use of i.p. infusion of recombinant interleukin-2 (rIL-2) was planned. The following dose levels were calculated: 0.1, 0.3, 1.0, 3.0 and 10 mg/m2/day for 14 days, but only the second levels were reached. In this trial the acute toxic effects at this dosage included cardiac ischemia, transient liver impairment and septic peritonitis. The maximum tolerated dose (MTD) was 0.3 mg/m2/day for 14 days. In addition, two patients developed peritoneal fibrosis. No objective responses were observed. Therefore, in order to explore the biological activity of low (nontoxic) doses, three patients (one untreated and two previously treated with rIL-2) were infused with 0.01 and 0.03 mg/m2/day for 7 days. Potentiation of cytolytic activities in peritoneal lymphocytes and activation of a lymphokine cascade in the ascitic fluid were observed at doses ranging from 0.03 mg/m2/day to 0.3 mg/m2/day. These findings in association with the toxic effects observed at the MTD suggest the use of the minimum effective dose for future locoregional immunotherapeutic protocols.

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↗