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N Colombo

Publications and source records attributed to N Colombo.

At least 73 records · Page 4Linked to original sources
PubMed1993

[Intraperitoneal administration of interferon gamma. An efficient adjuvant to the chemotherapy of ovarian cancers. Apropos of an European study of 108 patients].

One hundred and eight patients with residual epithelial ovarian cancer at second laparotomy, after first line plastine-based chemotherapy were treated with intraperitoneal rHU-interferon-gamma at a dose of 20 x 10(6) U/m2, twice a week for 3-4 months. 86% of the patients had residual macroscopic tumors and 33% bulky tumors (> 2 cm). From the 99 evaluable patients, 62 had an evaluative third laparotomy and nine additional patients a laparotomy. Complete pathologic and global response rates to interferon-gamma were 23 and 32% respectively. Age and tumor size were independently correlated with treatment response. Patients (n = 41) under the age of 60 with a tumor size less than 2 cm had a complete and global response rate of 42 and 54% respectively. Interferon-gamma was equally effective in chemo-resistant and chemosensitive tumors. Median duration of response was 21 months and median survival of responder patients was 86% at 2 years. In multivariate analysis, response to interferon-gamma was the most prominent prognostic factor of this population of patients with residual ovarian cancer.

Adult↗
PubMed1993

Advanced ovarian cancer. Dose intensity.

BACKGROUND: The rationale for dose intensity is based on pre-clinical observations in experimental model systems of cancer as well as upon retrospective studies correlating the impact of dose intensity upon response rates and survival. MATERIALS AND METHODS: A review has been performed based on trials attempting to compare the effects of two different dose intensities of either cisplatin or carboplatin, combinations of cisplatin and carboplatin, combined platinum with additional agents, and high-dose chemotherapy, regimens requiring hematologic support. RESULTS: The early phase II trials suggested that there may be an important dose response range over clinically achievable platinum doses, but randomized trials have failed to consistently show a clinically significant improvement with high-dose therapy. Reasons for this may be differences in patient selection, that total dose is the most important factor, or that a more than two-fold increase in dose intensity is needed to detect differences in response and survival rates. Phase I and II studies indicate that high, but short lasting, response rates can be achieved with high-dose therapy with haematopoietic support in refractory patients, but the toxicity is substantial. Paclitaxel dose intensity is presently being studied in several trials. CONCLUSIONS: Future trials of dose intensity should be focused upon patients with small volume disease and drug sensitive tumours.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Anti-tumor and immunomodulatory activity of intraperitoneal IFN-gamma in ovarian carcinoma patients with minimal residual tumor after chemotherapy.

Eight patients with epithelial ovarian carcinoma persisting after chemotherapy, selected for having a residual tumor no larger than 1 cm in diameter, were treated intra-peritoneally (i.p.) with recombinant interferon-gamma twice weekly for 3 months. Toxicity consisted of fever and malaise in all patients and a transient rise in hepatic enzyme levels in 3 patients. The cytotoxic function of peripheral blood and peritoneal tumor-associated lymphocytes (TAL) and macrophages (TAM), was studied using cell lines as targets. I.p. IFN-gamma augmented the cytotoxic activity of lymphocytes and mononuclear phagocytes: stimulation was more marked and more frequently observed with TAL and occasionally TAM than with blood effectors, suggesting preferential modulation at the site of tumor growth and IFN administration. Surgical laparotomy revealed that 1 patient had a complete response, 2 a partial response and 2 had stable disease, while 3 patients had progressive disease. In this small series of patients there was no obvious, strict correlation between immunomodulation by IFN-gamma and clinical response. These results indicate that, in contrast to its lack of activity in advanced ovarian carcinoma, IFN-gamma has definite immunomodulatory and antitumor activity in the presence of limited tumor burden.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Cisplatin-induced peripheral neurotoxicity is dependent on total-dose intensity and single-dose intensity.

The authors prospectively evaluated the effects of three different schedules of cisplatin (DDP) administration in 60 patients with advanced epithelial ovarian cancer. The individual total dose of DDP was 450 mg/m2 in all three groups, and the anti-cancer response at the end of treatment was similar for the different regimens. The clinical and neurophysiologic results confirmed that axonal sensory neuropathy occurred after the standard administration of DDP (75 mg/m2 in 3-week cycles) and probably not only the peripheral, but also the central sensory pathway, was involved. Although the total dose of the drug was identical, the two less conventional schedules were less neurotoxic. These results suggest that not only the total-dose intensity, but also the single-dose intensity are relevant in the onset of DDP-induced sensory neuropathy; therefore, the use of less neurotoxic schedules may prevent or reduce sensory nerve damage.

Aged↗
PubMed1992

In search of specific cytotoxic T lymphocytes infiltrating or accompanying human ovarian carcinoma.

Lymphocytes infiltrating human ovarian carcinoma obtained directly from the tumour mass (tumour-infiltrating lymphocytes, TIL) or from the carcinomatous ascites (tumour-associated lymphocytes, TAL) were expanded in vitro in long-term cultures with interleukin-2 and tested for their specific cytolytic activity. Killing of the autologous tumour was detected only in a proportion of the patients, less frequently in TIL compared to TAL. In fact two out of ten TIL and four out of nine TAL cultures tested showed significant levels of lysis against the autologous tumour. This cytotoxic activity was not restricted to the autologous tumour, as other tumour cell lines, including non-ovarian ones, were lysed as well. The cultures that were not cytotoxic against the autologous tumour were in most cases able to lyse other tumour cell lines of ovarian or other histology. Cloning of TIL from one patient was performed: of 22 clones tested, 4 displayed higher cytotoxicity against the autologous tumour compared to the uncloned population and 3 out of these 4 did not kill an irrelevant carcinoma cell line. In order to stimulate the expansion of putative specific effectors we performed mixed lymphocyte/tumour cultures (MLTC) with autologous or allogeneic tumour cells. No stimulation of cytotoxicity against the autologous tumour was detected after MLTC in nine different TAL populations, using autologous or allogeneic tumours as stimulators. On the contrary, peripheral blood lymphocytes from two patients after MLTC with the autologous tumour showed increased killing of the autologous and decreased killing of an allogeneic target. In conclusion TIL and TAL from ovarian carcinoma expanded in vitro with interleukin-2 usually have non-MHC-restricted cytotoxicity and variable degrees of reactivity against the autologous tumour. A preferential killing for the autologous tumour was not observed even after MLTC. These results do not exclude the existence of tumour-specific cytotoxic T lymphocytes in ovarian carcinoma; nevertheless they suggest that putative specific effectors have very low frequency and that culture techniques for expanding their growth more selectively are still to be optimized.

Cells, Cultured↗
PubMed1991

Phase I and pharmacologic evaluation of intraperitoneal 5-fluoro-2'-deoxyuridine.

Intraperitoneal (i.p.) 5-fluoro-2'-deoxyuridine (Floxuridine, FUdR, FdUrd) was evaluated in a phase I study at a starting level of 500 mg given on 1 day in 2 I 1.5% dialysate. Escalations within patients were allowed every other cycle. A total of 23 patients (age, 32-78 years) received 108 treatment courses. Local tolerance at all dose levels was excellent, with no cases of drug-related peritonitis being observed. Nausea and vomiting increased in severity in relation to dose and was universal at greater than 3,000 mg x 3 days. One patient each developed grade 1 mucositis as well as diarrhea at a dose of 3,000 mg x 3 days and leukopenia and thrombocytopenia at 5,000 mg x 3 days. Peritoneal fluid (PF) and plasma (PL) FdUrd profiles were monitored by an HPLC method in 13 subjects, with 7 being studied serially at 2-4 increment doses for up to 6 h. Profiles that exhibited apparent linear pharmacokinetics gave PF drug levels 2-4 logs higher than the PL counterparts, with the latter essentially declining in parallel to the former, indicating that the disposition of FdUrd from the peritoneal compartment is rate-determining. The mean terminal half-life for PF FdUrd was found to be 115 min and mean peritoneal clearance was 25 ml/min. The vast differences in drug levels and AUC found between the PF and the PL profiles suggests a high systemic clearance of FdUrd, which was confirmed in two patients receiving 2 g FdUrd by short i.v. infusion. A disproportionate increase in the plasma FdUrd levels and the corresponding AUC values was found with increasing dose, suggesting a disproportionate increase in the systemic partitioning of FdUrd when doses were escalated within a patient. Substantial levels of peritoneal 5-fluorouracil (FUra) were also detected in most of the subjects. Thus, FdUrd was found to have several desirable properties for i.p. administration: (1) a 2- to 4-log pharmacologic advantage. (2) the absence of local toxicities, and (3) a favorable antitumor spectrum and some evidence of antitumor effects in this phase I and pharmacology study. A 3,000-mg dose given in 2 1 1.5% dialysate for 3 consecutive days exhibited antitumor activity and produced no systemic toxicity except nausea and vomiting, which was controlled by antiemetics. This dose schedule is therefore recommended for phase II trials directed against small-volume disease in the peritoneal cavity, such as may be found in some stages of ovarian and gastrointestinal cancers.(ABSTRACT TRUNCATED AT 400 WORDS)

Ascitic Fluid↗
PubMed1991

Consolidation with intraperitoneal cisplatin in first-line therapy of advanced ovarian cancer.

Seventy-five patients with advanced epithelial ovarian cancer were treated with a combined modality regimen of systemic, induction chemotherapy followed by intraperitoneal therapy (IPT). All patients underwent initial surgery for staging and/or cytoreduction followed by cisplatin 20 mg/m2 intravenously (IV) for 5 days and cyclophosphamide 600 mg/m2 on day 4 every 3 to 4 weeks for two to four cycles. Patients were then evaluated for IPT and, if eligible, had an intraperitoneal (IP) catheter placed. IPT consisted of cisplatin 60 mg/m2 in 2 L on day 1 and IV cyclophosphamide 600 mg/m2 on day 2 every 3 weeks for three to six cycles. Patients who demonstrated a clinical complete response (CCR) were then referred for second-look laparotomy (SLL). Of 71 patients who completed the induction phase, 53 (75%) were eligible for IPT, and 49 patients entered the therapy phase. Toxicity of the combined modality approach was acceptable and did not differ from our previous experience using the same drugs systemically. Thirty-two of the 49 patients who completed IPT achieved a CCR, which was confirmed by SLL in 20 patients. Twenty recurrences were documented in the 32 CCR patients, 13 occurred in patients after SLL. Projected median survival of all patients is 38 months. Median survival correlated with amount of residual disease following initial surgery (23 months for bulky v 45 months for minimal residual; P less than .001) and with performance status ([PS]; 24 months for PS 2, 3 v greater than 46 months for PS O; P less than .001). Patients who presented with bulky tumors were less likely to reach the consolidation IPT phase. Incorporation of IP cisplatin into the first-line regimen for treatment of ovarian cancer does not appear to have major impact on the survival of all treated patients when compared with our historical control series. Combined IV and IPT cisplatin and cyclophosphamide is feasible with acceptable toxicity. Its impact on response and survival may be limited to only "good-prognosis" patients.

Adult↗
PubMed1990

Intraperitoneal recombinant gamma-interferon in patients with recurrent ascitic ovarian carcinoma: modulation of cytotoxicity and cytokine production in tumor-associated effectors and of major histocompatibility antigen expression on tumor cells.

Seven patients with advanced epithelial carcinoma and ascites, relapsing after two or more regimens of standard chemotherapy, have been treated with recombinant gamma-interferon (rIFN-gamma) i.p., via a permanent catheter. rIFN-gamma (Immuneron; Biogen; 0.5 mg = 10(7) IU in 2 liters of saline) was administered 3 times a week, on alternate weeks, for a total of nine courses. No major toxicities were observed: mild fever, malaise, and a flu-like syndrome occurred in all patients. The modulation of immunological parameters was studied. Cytotoxic activity of immunocompetent cells against tumor cell lines was measured both in the peritoneal compartment and in peripheral blood mononuclear cells. A significant increase of cytotoxicity of tumor-associated macrophages was observed in 5 of 7 patients and in 4 of 7 patients with tumor-associated peritoneal lymphocytes. Circulating effector cells were only occasionally stimulated. Tumor-associated macrophages isolated from the ascitic fluid and stimulated with lipopolysaccharide produced higher amounts of interleukin 1 in 5 of 6 patients tested, while interleukin 6 production by unstimulated tumor-associated macrophages was augmented in 2 of 2 patients after rIFN-gamma treatment. Freshly isolated ovarian carcinoma cells from the ascitic fluid has a variable, although usually low, expression of HLA-DR antigens. rIFN-gamma treatment caused a marked increase in HLA-DR expression in all patients tested. Expression of HLA class I antigens was negative in 2 of 5 patients and was strongly increased in 1 of the 2 after treatment. The observation that rIFN-gamma administered i.p. activates in situ effector cells and augments major histocompatibility antigen expression in tumor cells, with minimal toxicity, encourages further efforts to investigate its therapeutic potential in ovarian carcinoma.

Ascites↗
PubMed1990

Selection of cancer chemotherapy for a patient by an in vitro assay versus a clinician.

One hundred thirty-three patients with advanced metastatic cancer were randomized to receive single-agent chemotherapy selected by either a medical oncologist or an in vitro capillary cloning system. Thirty-six of the 65 patients (55%) who were randomly assigned to selection of a drug by the clinician actually received a drug; these patients were able to be evaluated for clinical response. Of these 36 patients, one had a partial tumor response (3%). Only 19 of the 68 patients (28%) who were randomly assigned to selection of a drug by the capillary system actually received a drug; these patients were able to be evaluated for clinical response. Of these 19 patients, four (21%) had partial tumor responses. In the assessable patients (36 in the clinician's choice group, 19 in the capillary cloning group), the partial response rate was superior for drug selection by the capillary cloning system (P = .04). For all patients randomly assigned to a group (65 in the clinician's choice group, 68 in the capillary cloning group), the response rate was not significantly different (1.5% and 5.9%, respectively; P = .37). When overall survival rates for patients in the two groups were compared, there was no difference. We conclude that drug sensitivity testing in capillary tubes can improve the response rate for patients with advanced malignancies. This improved response rate, however, does not translate into improved survival times for these patients.

Antineoplastic Agents↗
PubMed1990

In vitro and in vivo effects of cisplatin on the generation of lymphokine-activated killer cells.

Pretreatment of human peripheral blood lymphocytes (PBL) with cisplatin (CDDP) before in vitro culture with interleukin-2 (IL-2) inhibited the generation of lymphokine-activated killer (LAK) cells and strongly inhibited proliferation. This inhibition was dose dependent, was significant only at concentrations greater than 6 microM, and it required exposure to the drug for more than 1 hour. This period of IL-2 unresponsiveness was maximum at 6 hours, but was spontaneously recovered within 24-48 hours and was more rapidly restored by increasing dosages of IL-2. Because inhibition of the generation of LAK cells by CDDP was observed only at relatively high levels of exposure to the drug (greater than 6 microM for greater than 1 hr), it was important that we explore the in vivo significance of these findings. The peripheral blood lymphocytes from patients bearing ovarian adenocarcinoma collected 1 hour after an iv infusion of 50 mg of CDDP/m2 were not inhibited, compared with those collected immediately before therapy. Relatively high levels of exposure to CDDP are required for inhibition of the generation of new cytotoxic effectors, most likely because of its antiproliferative effect. These results may bear relevance to approaches involving the combined use of CDDP and IL-2-LAK.

Adenocarcinoma↗
PubMed1990

Phase II study of esorubicin (4'deoxydoxorubicin) in anthracycline naive patients with ovarian cancer.

Sixteen patients with metastatic ovarian cancer who had not previously been treated with anthracyclines were treated with 4'deoxydoxorubicin at a dose of 30 mg/m2 intravenously every 3 weeks. There were no clinical responses in this group of patients. Toxicities were infrequent with neutropenia and thrombocytopenia being dose limiting. Nausea and vomiting occurred in only 4 patients. We conclude that 4'deoxydoxorubicin is an inactive drug in this patient population and does not warrant further investigation in this disease.

Adult↗
PubMed1990

Value of magnetic resonance imaging in spontaneous extradural spinal hematoma due to vascular malformation: case report.

A case of spinal cord compression due to spontaneous extradural spinal hematoma is reported. A spinal arteriovenous malformation was suspected on the basis of magnetic resonance imaging. Early surgical exploration allowed a complete neurological recovery. The vascular malformation was histopathologically confirmed. The role of magnetic resonance imaging in the evaluation of acute spinal cord compression syndromes is stressed.

Arteriovenous Malformations↗
PubMed1990

Prognostic factors in advanced epithelial ovarian cancer. (Gruppo Interregionale Cooperativo di Oncologia Ginecologica (GICOG)).

The data on 914 patients enrolled in four randomised trials in advanced ovarian cancer, consecutively conducted by the same cooperative group between 1978 and 1986, were analysed with the aims of: (1) determining the impact of selected prognostic variables on survival; (2) finding, from the interaction of favourable prognostic factors and treatment, an approximate estimate of the magnitude of the survival advantage associated with the use of platinum-based combination chemotherapy. The overall 3-year survival in this series of patients is twice that reported historically (22%; 95% CL 18.7-25.4). The proportional hazard regression model was used to perform the analysis on survival. Residual tumour size, age, FIGO stage and cell type were all independent determinants of survival. Differences in survival from the various prognostic groups were impressive with 5-year survival rates ranging from 7 to 62%. However, these differences were not qualitative (i.e. the kinetics of survival were similar for the best and the worst groups) suggesting that current prognostic factors are of little use for selecting 'biologically' different sub-populations. Platinum-based regimens were associated to an overall prolonged median survival, but this benefit was not observable in the subgroup with most favourable prognosis (less than 2 cm residual tumour size). The implications of these observations for clinical research and ovarian cancer patients care are discussed.

Age Factors↗
PubMed1990

Intraperitoneal carboplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy.

From August 1985 to November 1989 we conducted a trial of intraperitoneal (IP) carboplatin including a dose-escalation design in 25 women with advanced gynecologic malignancies. All had extensive prior therapy with cisplatin (median cumulative dose, 525 mg/m2). Carboplatin was administered IP in 2 L of 1.5% dextrose with a 4-hour dwell time every 4 weeks for six cycles at a starting dose of 200 mg/m2. Patients with reduced creatinine clearance (30 to 60 cc/min) were escalated more slowly than those with high (greater than 60 cc/min) clearance. Thrombocytopenia was dose-limiting and often more severe in patients with compromised renal function; there was no local drug toxicity. The median time of follow-up is 25 months. Complete responses (CRs) were documented in six of 23 assessable patients (26%) by repeat laparotomy, and an additional 11 patients (48%) had no disease evident by noninvasive restaging. Five of the CRs and six of the patients with no clinically evident disease have relapsed from 3 to 40 months after therapy. Six patients (26%) are alive and free of disease 8 to 47 (median, 20) months after therapy. IP carboplatin is effective against relapsed ovarian cancer, even after prior cisplatin therapy.

Adenocarcinoma↗
PubMed1989

Intraperitoneal and subcutaneous xenografts of human ovarian carcinoma in nude mice and their potential in experimental therapy.

Human ovarian carcinomas (HOC) were established s.c. and i.p. in nude mice and the biological characteristics were investigated for 4 xenografts. HOC8 and HOC18, derived respectively from a primary tumor of the ovary and a pleural effusion (from 2 different patients) were established s.c. in nude mice. HOC10 and HOC22, derived from the ascites of 2 patients, were directly established as ascites after i.p. injection in nude mice. The s.c. and i.p. growth behavior of the 4 HOC lines was investigated. HOC18, HOC8 and HOC22 cells produced progressively growing tumor after s.c. injection but HOC10 ascites would not grow s.c. The cell suspension derived from HOC18 only produced carcinomatosis upon i.p. injection, while HOC8 cells produced both ascites and carcinomatosis. The 2 ascites HOC10 and HOC22 produced ascites in nude mice, but only HOC22 formed i.p. carcinomatosis. Histopathological characteristics of the patients' primary tumors persisted in nude mice, regardless of the site of tumor implantation. DNA histograms of the xenografts closely matched the patients' tumors and remained stable at different passages. Cisplatin, adriamycin and cyclophosphamide given i.v. were tested against HOC8 and HOC18 growing s.c. and HOC22 and HOC10 growing i.p. HOC8 showed a significant response to DDP and almost no sensitivity to ADR and CTX. HOC18 showed only moderate growth delay with all 3 drugs. Mice bearing HOC10 and HOC22 ascites had a prolonged survival time after DDP and ADR treatment.

Animals↗