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N Colombo

Publications and source records attributed to N Colombo.

At least 91 records · Page 5Linked to original sources
PubMed1989

Phase II study of carboplatin in recurrent ovarian cancer: severe hematologic toxicity in previously treated patients.

Carboplatin (CBDCA) is a second-generation cisplatin analog that has shown activity in early clinical trials. Its spectrum of toxicity is quantitatively and qualitatively different from that of the parent compound. Between November 1984 and September 1986 we conducted a phase II trial of CBDCA in 46 women with epithelial ovarian cancer. All patients had undergone at least one prior chemotherapy regimen; 41 (89%) had previously received cisplatin (mean cumulative dose, 540 mg/m2). The CBDCA dose was based on renal function and was injected i.v. once every 4 weeks. Patients were stratified on the basis of baseline creatinine clearance: those with a baseline creatinine clearance of greater than or equal to 60 ml/min received 400 mg/m2 CBDCA; those with a creatinine clearance between 30 and 60 ml/min received an initial dose calculated according to a previously published formula that corrected for renal insufficiency and projected nadir platelet counts of 75,000/mm3. Of 41 evaluable patients, 6 (15%) had an objective response [2 complete responses (CRs); 4 partial responses (PRs)]; 5 of the 6 responders had previously responded to cisplatin treatment. No responses were observed in 12 patients who had not responded to prior cisplatin therapy. Significant hematologic toxicity was seen. Of 18 patients with a creatinine clearance of greater than or equal to 60 ml/min (dose, 400 mg/m2), 6 had nadir platelet counts of less than 25,000/mm3, 4 with symptomatic bleeding. Of the 21 evaluable patients for whom the dose-modification formula was applied, 10 had nadir platelet counts of less than 75,000/mm3; 5 had counts of less than 50,000/mm3. CBDCA has activity even in patients who have previously undergone extensive cisplatin therapy; however, its toxicity is variable and thrombocytopenia is dose-limiting. We did not confirm the ability of the above-mentioned formula to calculate the CBDCA dose and accurately predict the nadir platelet count for all patients. Other factors, such as prior radiotherapy, may also be important in the dosing of CBDCA in pretreated patients.

Acute Disease↗
PubMed1988

Human ovarian tumors in primary culture: growth, characterization and initial evaluation of the response to cis platinum treatment in vitro.

A novel cell culture system is reported for the growth of ovarian tumors. Two approaches were developed to isolate tumor cells, one for ovarian carcinomas and the other for benign cystomas or borderline cystadenomas, which yield virtually pure tumor-cell clusters. The plating efficiency exceeded 10% in approximately 80% of the processed surgical specimens. Cells grown in a newly developed KOV medium (a modification of MCDB 151 supplemented with 6 defined growth factors and a moderate amount of FBS) had an average growth rate of 0.23 population doublings/day. Primary tumor-derived cultures, including those derived from cystomas, were analyzed by flow cytometry demonstrating a DNA heteroploid content in 55% of the cases. The neoplastic origin of the cells in culture was further confirmed by 3 monoclonal antibodies (OC125; MOv2; MOv19) with high specificity against epithelial ovarian malignancies. Cultures were tested with cis-DDP to determine their suitability for pharmacological studies. Exposure to the drug (from 10 to 80 microM for 1 hr) resulted in variable cell-killing responses, and the prominent effect on cell-cycle progression in primary cultures was a prolonged arrest in S phase. The formation and persistence of DNA-ISC caused by an exposure to 40 microM cis-DDP for 1 hr was studied by alkaline elution in 6 different tumor-derived cultures. DNA-ISC equivalents were highest between 9 and 24 hr after treatment and were repaired only to a limited extent within 48 hr of recovery time. The present study confirms the usefulness of this culture system for pharmacological studies of active chemotherapeutic agents against human ovarian tumors.

Antibodies, Monoclonal↗
PubMed1988

DR antigen expression on ovarian carcinoma cells does not correlate with their capacity to elicit an autologous proliferative response.

Expression of HLA-DR antigens by purified preparations of human ovarian carcinoma cells freshly isolated from surgical specimens was examined in parallel with the capacity of tumor cells to elicit a blastogenic response from autologous lymphocytes in mixed lymphocyte-tumor culture (MLTC) assay. Of 21 tumor preparations, 11 (52%) reacted with monoclonal antibodies 279 and/or 949 specific for a monomorphic determinant of HLA-DR antigens, with heterogeneous positivity, ranging between 30% and 95%. In this series of patients positive MLTC occurred in 8/21 individual experiments. The HLA-DR expression was proportionally similar in tumors giving positive MLTC (4/8 = 50%) and negative MLTC (7/13 = 53%). The lack of correlation between DR expression on tumor cells and stimulatory activity in autologous MLTC and the fact that DR-negative tumors could induce lymphocyte stimulation, support the hypothesis that blastogenesis occurs upon recognition of tumor-associated antigens, different from DR molecules, possibly tumor-specific antigens.

Adult↗
PubMed1988

The disposition of carboplatin in ovarian cancer patients.

Carboplatin was given as a 30-min infusion to 11 ovarian cancer patients at doses of 170-500 mg/m2. The ages, weights, and creatinine clearances (Clcr) ranged from 44 to 75 years, from 44 to 74 kg, and from 32 to 101 ml/min, respectively. Plasma, plasma ultrafiltrate (PU), and urine samples were obtained at appropriate times for 96 h and were analyzed for platinum. The PU and urine were also analyzed for the parent compound by HPLC. In patients with a Clcr of about 60 ml/min or greater, carboplatin decayed biexponentially with a mean t1/2 alpha of 1.6 h and a t1/2 beta of 3.0 h. The mean (+/- SD) residence time, total body clearance, and apparent volume of distribution were 3.5 +/- 0.4 h, 4.4 +/- 0.85 l/h, and 16 +/- 3 l, respectively. Cmax and AUCinf values increased linearly with dose, and the latter values correlated better with the dose in mg than in mg/m2. No significant quantities of free, ultrafilterable, platinum-containing species other than the parent compound were found in plasma, but platinum from carboplatin became protein-bound and was slowly eliminated with a minimal t1/2 of 5 days. The major route of elimination was excretion via the kidneys. Patients with a Clcr of 60 ml/min or greater excreted 70% of the dose as the parent compound in the urine, with most of this occurring within 12-16 h. All of the platinum in 24-h urine was carboplatin, and only 2%-3% of the dosed platinum was excreted from 48 to 96 h. Patients with a Clcr of less than about 60 ml/min exhibited dose-disproportional increases in AUCinf and MRT values. The latter were inversely related to Clcr (r = -0.98). Over a dose range of 300-500 mg/m2, carboplatin exhibited linear, dose-independent pharmacokinetics in patients with a Clcr of about 60 ml/min or greater, but dose reductions are necessary for patients with mild renal failure.

Adult↗
PubMed1988

MR imaging of cavernous sinus involvement by pituitary adenomas.

The ability of high-resolution MR imaging (1.5 T) to detect invasion of the cavernous sinuses by pituitary adenoma was determined through a retrospective review of 74 patients. These patients were divided into three groups: 25 normal subjects, 24 subjects with invasive pituitary adenomas, and 25 subjects with noninvasive pituitary adenomas. A fourth group of 30 patients, who subsequently underwent surgery for pituitary adenoma, was evaluated prospectively by MR for the presence or absence of cavernous sinus invasion. Several features were analyzed: (1) the detectability of the medial and lateral dural margins of the cavernous sinus (2) the size and variation in intensity of compartments within the cavernous sinus (3) the relationship of endocrine function to the surgical and MR appearance of the cavernous sinus and (4) carotid artery displacement or encasement by tumor. The normal cavernous sinuses were usually symmetric, but their sizes varied. The lateral dural margin of the cavernous sinus was always recognized on MR as a linear, discrete, low-intensity area. The medial dural margin (pituitary capsule) was seen on MR in only two of the 25 normal patients. In all 24 patients with cavernous sinus invasion involvement was unilateral and was most common with laterally positioned prolactin or adrenocorticotropic hormone secretory adenomas. Invasion of the cavernous sinus was suspected by MR in only two of the 13 invasive microadenomas and was questionable in three. In 10 of the 11 macroadenomas with surgically proved dural invasion, MR demonstrated an asymmetric increase in size and intensity of the superior and inferior cavernous sinus compartments. Noninvasive macroadenomas compressed and displaced the cavernous sinus bilaterally. The prospective MR evaluation of 30 patients undergoing surgery for pituitary tumor revealed a sensitivity for predicting cavernous sinus invasion of 55%, a specificity of 85.7%, a positive predictive value of 62.5%, and a negative predictive value of 81.8%. No feature permitted certain distinction between invasive and noninvasive microadenomas, as the medial dural wall of the cavernous sinus could not be reliably identified. The most specific sign of cavernous sinus invasion was carotid artery encasement.

Adenoma↗
PubMed1987

Methotrexate with citrovorum factor in low-risk gestational trophoblastic tumor.

From January 1976 through December 1985, methotrexate (MTX) with citrovorum factor (CF) was administered as primary treatment to 57 patients with low-risk gestational trophoblastic tumor (GTT); 51 patients were non-metastatic and 6 were metastatic GTT. The median number of courses needed to achieve biochemical remission was two (range, 1-7). Complete remission was attained in 95% of non-metastatic GTT patients with postmolar persistent trophoblastic disease, but when choriocarcinoma was histologically confirmed, this fell to 60%. The cure rate of metastatic GTT patients was only 50%. The overall remission rate with the MTX-CF combination was 84.2%. Toxicity was mild, consisting of myelosuppression and mucositis. Fifteen patients were resistant to MTX-CF, or relapsed subsequently, but they all achieved remission with chemotherapy rescue treatment (VP 16 alone, EMA/CO, CHAMOCA). Two patients required a pulmonary lobectomy. They are all still alive in biochemical remission with a median survival of 54 months. Our experience suggests that drug resistance and relapse rate seem related to a beta-HCG value higher than 10(4), an enlarged uterus with myometrial deep involvement, and a histologically confirmed diagnosis of choriocarcinoma. In conclusion, the MTX-CF combination is effective in postmolar GTT, whereas a different therapeutic approach may be considered for a "special" low-risk group of patients, on the basis of prognostic factors.

Female↗
PubMed1987

Magnetic resonance diagnosis of intramedullary tumors of the spinal cord.

Fifty patients with intramedullary space occupying lesions were studied with MR from October 1983. Of these 32 were operated on and histological diagnosis together with gross morphological description was available. MR findings were reviewed in search for morphological and signal characteristics capable of providing a better preoperative diagnosis. There were 11 astrocytomas, 10 ependymomas, 5 vascular lesions and 6 "gliomas". All lesions usually had signal characteristics different from those of the normal cord, mainly because of prolonged T1 and T2 relaxation times. No specific patterns related either to morphology or signal were found, capable of differentiating the two main histological types. Vascular malformations may be suspected from the presence of serpiginous areas without signal. Tumor nodules within cysts can however be well recognized, thus providing the neurosurgeon with very useful preoperative information. Some characteristics of signal and morphology, are more common for one or the other of the two main groups of tumors. A tumor involving all the cord with a homogeneously prolonged T2 relaxation time is most likely to be an astrocytoma. A small nodule with signal close to normal parenchyma, associated with extensive cysts, is most likely to be an ependymoma.

Adult↗
PubMed1987

Posterior pituitary gland: appearance on MR images in normal and pathologic states.

T1-weighted magnetic resonance (MR) images of the pituitary gland and sella turcica routinely demonstrate a region of high signal intensity in the neurohypophysis. High-resolution MR imaging studies of the sella turcica in 200 subjects with a normal or abnormal sella were analyzed. The hyperintensity was found in the images of about 90% of healthy subjects and patients with microadenoma, in only 43% of patients with macroadenoma, and in 12% of patients with empty sellae. The signal was absent in several patients with functional or anatomic abnormalities of the hypothalamic-hypophyseal axis. It is concluded that the high signal intensity in the posterior lobe of the pituitary gland is present in most healthy individuals and that its absence in many patients with large intrasellar masses and empty sellae is due to compression of posterior lobe tissue. Its absence in diabetes insipidus further suggests a relationship between hyperintensity and the functional status of the hypothalamic-hypophyseal axis.

Adenoma↗
PubMed1987

A reassessment of the role of second-look laparotomy in advanced ovarian cancer.

Thirty-nine patients with stage III and IV epithelial ovarian cancer who underwent second-look laparotomy (SLL) at New York University Medical Center and 11 eligible patients who did not undergo reexploration were retrospectively studied with follow-up from 24 to 105 months after diagnosis. Sixteen patients (41%) were found to have macroscopic disease, six (15%) microscopic tumor, and 17 (44%) no disease at SLL. Five of 22 patients who received further therapy based on positive SLL findings have remained without clinical evidence of disease 17 to 65 months after SLL. Nine of 17 patients with negative SLL, in whom treatment was stopped, recurred 8 to 52 months after SLL, five in extraperitoneal sites only. Five of 11 patients not undergoing SLL recurred 16 to 39 months after diagnosis, four intraperitoneally. There was no significant difference in survival between the second-look and no second-look groups for the period of study. Clinical trials are needed to determine if SLL influences longer-term survival and if continued treatment is indicated in a high-risk subgroup despite negative SLL. The value of SLL is limited by the efficacy of second line therapy. The role of routine SLL outside an investigational setting is questioned.

Female↗
PubMed1986

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↗
PubMed1986

Magnetic resonance imaging of spinal cord hemangioblastoma.

We retrospectively reviewed the magnetic resonance (MR) studies in nine patients with spinal cord hemangioblastoma. Five patients were studied with a low field magnet (0.35 T/0.5 T) and four with a high field magnet (1.5 T). Six tumors were thoracic and three cervical in location. Magnetic resonance imaging (MRI) was positive in all the nine patients. MRI permitted a specific diagnosis prior to angiographic evaluation of the cord in three patients. The most characteristic findings in such tumors were: an intramedullary vascular nodule, enlarged drainage vessels, diffuse enlargement of the cord, and/or intramedullary cyst. The high field magnet showed a greater sensitivity in detecting vascularity within the nodule and draining vessels than did the low field magnet. MRI should be the first procedure in patients with myelopathy and subarachnoid bleed of spinal origin and for screening patients with von Hippel-Lindau disease.

Adult↗
PubMed1985

Tumor-derived chemotactic factor(s) from human ovarian carcinoma: evidence for a role in the regulation of macrophage content of neoplastic tissues.

Supernatants from freshly disaggregated human ovarian carcinomas maintained in vitro for 24 hr, from primary ovarian carcinoma cultures (4-6 days in culture) and from established ovarian cancer cell lines were examined for chemotactic activity on blood monocytes in blind-well chemotaxis chambers. Tumor-cell culture supernatants induced migration of peripheral blood monocytes across polycarbonate filters with considerable heterogeneity among different tumors. Induction of migration occurred only in the presence of a gradient between the lower and upper compartments of the chamber. Chemotactic activity was characterized by means of supernatants from primary ovarian carcinoma cultures. Chemotactic factor(s) was (were) produced in serum-free conditions and the production was inhibited by emetine but not by mitomycin C. The activity was destroyed by exposure to proteolytic enzymes and by heating at 100 degrees C but was unaffected by RNase, DNase, lipase and exposure to extreme pH values or heating at 56 degrees C. Upon fractionation on Sephadex G 75, the activity eluted as a single peak in the cytochrome C region, corresponding to an apparent molecular weight of about 12 kd. The percentage of macrophages was assessed in 25 freshly disaggregated tumor specimens. Ovarian carcinomas were heterogeneous in their macrophage content with values ranging from 4 to 36%. A significant (r = 0.62; p = 0.00097), though far from absolute, correlation was found between chemotactic activity of culture supernatants and percentage of tumor-associated macrophages. Tumor-derived chemotactic factor(s) could be one of the mechanisms involved in the regulation of the macrophage content of human ovarian carcinomas.

Carcinoma↗
PubMed1985

Intraperitoneal administration of interferon beta in ovarian cancer patients.

Eight patients with advanced ovarian carcinomas resistant to conventional chemotherapy were injected with interferon (IFN) beta (3 X 10(6) U) intraperitoneally twice a week. Seven subjects had ascites. Side effects included abdominal pain, fever, and constipation, but no hematologic toxicity was observed. Growth of solid tumor lesions was unaffected by IFN beta, with the possible exception of one patient who had stable disease. IFN beta intraperitoneally inhibited completely the formation of ascites in four of seven patients with effusions. Natural killer (NK) cell activity was measured in peripheral blood and tumor-associated lymphocytes (PBL and TAL). Using stringent criteria that included repeated assessment of baseline activity, a clear cut increase in NK cytotoxicity of TAL was detected in two of six subjects from whom TAL could be purified. Augmentation of NK activity was restricted to the peritoneal compartment with no effect on PBL. Studies on biologic response modifiers encompassing an analysis of events taking place at sites directly involved by neoplasia may provide an opportunity for generating information on the in situ regulation of tumor-associated host defense mechanisms in humans.

Adult↗
PubMed1985

Hexamethylmelamine, adriamycin, and cyclophosphamide (HAC) versus cis-dichlorodiamineplatinum, adriamycin, and cyclophosphamide (PAC) in advanced ovarian cancer: a randomized clinical trial.

After stratification according to diameter of the largest residual tumor, 120 previously untreated ovarian cancer patients were randomized to receive adriamycin and cyclophosphamide in combination with hexamethylmelamine (HAC) or cis-dichlorodiamineplatinum (PAC). The surgical response rates were 66% to HAC and 70% to PAC, with median times to progression of 14 and 22 months and median survival times of 23 and 24 months, respectively. In patients with residual tumor greater than 2 cm the surgical response rates to HAC and PAC were 56% and 63%, with complete response rates of 13% and 21%, respectively. In two of five complete responders to HAC there has still been no progression at 38 and 48 months, with a median response duration of 25 months. Only one of the nine complete responders to PAC has relapsed, at 33 months, while in the eight others response is maintained at follow-up times of 35-64 months. Myelosuppression was generally mild and similar in the two arms. No significant nonhematological toxicity was reported. It is concluded that at a median follow-up time of 36 months HAC is as effective as PAC in terms of response, duration of remission, and survival in previously untreated advanced ovarian cancer.

Adolescent↗
PubMed1985

Follow-up study of enzymuria and beta 2 microglobulinuria during cis-platinum treatment.

Twenty patients with epithelian ovarian cancer treated with DDP (cis-diammine-dichloroplatinum II) 50 mg/m2 were followed for 24 weeks in order to assess the nephrotoxicity of the drug. Ten patients received the total dose in one day with heavy osmotic hydration (Group A), and for the other 10 the dose was subdivided over 3 consecutive days (Group B). The renal tubular toxicity of DDP treatment was evaluated over a total of 120 courses. After the first DDP administration, there was a prompt, reversable and dose-dependent increase in the urinary excretion of beta 2 microglobulin with no difference between the two groups: Group A from 405 to 990 and Group B from 109 to 585 ng/mg creatinine. An increase always occurred during subsequent courses, but it was significantly lower in Group B after the sixth course, from 125 to 331 ng/mg creatinine. A similar pattern was found for the urinary excretion of N-acetyl-glucosaminidase (NAG), a lysosomal enzyme of tubular origin. The percentage fraction of urinary sodium excretion (FeNa%) increased after each dose of DDP; Group A from 0.82 to 2.30 and Group B from 0.68 to 2.53. This effect was reversible and it occurred to the same extent during the subsequent courses. There was no impairment of the glomerular filtration rate. Thus, enzymuria and beta 2 microglobulin excretion are a sensitive tool to reveal minor tubular damage. Their use to predict serious renal dysfunction in longitudinal studies, however, seems questionable.

Acetylglucosaminidase↗
PubMed1985

Antiemetic activity of two different high doses of metoclopramide in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research.

High-dose metoclopramide has been proposed as an effective antiemetic agent in patients treated with cisplatin. Its optimal dosage schedule, however, has not yet been completely defined. We report the results of a multicenter, double-blind, randomized clinical trial where the efficacy and safety of two fixed high-dose regimens of metoclopramide (60 and 120 mg, respectively) have been tested in 112 patients receiving cisplatin treatment. No statistically significant difference has been found between the two groups. In patients treated with cisplatin at doses greater than 100 mg/m2, the higher dose regimen seems more efficacious, but this result should be confirmed in a larger group of patients. Treatment was generally well-tolerated. However, a consistent percentage of patients (about 60%) still present with vomiting, and this makes further investigation necessary.

Adult↗