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Biomedical subjects

O Vinante

Publications and source records attributed to O Vinante.

32 records · Page 2Linked to original sources

Cisplatin, etoposide, and ifosfamide in non-small cell lung carcinoma. A phase II randomized study with cisplatin and etoposide as the control arm.

A Phase II randomized study testing the combination of cisplatin, etoposide, and ifosfamide (PEI) in non-small cell lung cancer (NSCLC) was performed. The standard combination of cisplatin and etoposide (PE) was used as the control arm. Since January 1987, 78 patients were enrolled and then stratified for previous treatments and performance status (PS). The response rate (RR) of PEI was 26% (95% confidence limits [95 CL], 12% to 40%), with one complete response (CR). The RR of PE was 26% (95 CL, 13% to 39%), with no CR. The median response duration was 5 months (range, 2 to 13 months) for PEI and 4 months (range, 2 to 6 months) for PE. The median survival time was 6 months (range, 1 to 22+ months) for PEI and 7 months (range, 1 to 21+ months) for PE. Leukopenia at recycling was similar in both arms (25% for PEI and 29% of PE). The median leukocyte nadir was 2100/microliters (range, 430 to 4870/microliters) for PEI patients and 3150/microliters (range, 500 to 5000/microliters) for PE patients. Three patients had a drug-related death secondary to infections. This Phase II randomized study suggested that the combination of cisplatin plus etoposide and ifosfamide produces results similar to those obtainable with cisplatin and etoposide.

Adenocarcinoma↗

Cisplatin plus vindesine versus cisplatin plus VP16 versus doxorubicin plus cytoxan in non-small-cell carcinoma of the lung. A randomized study.

From March 1981 to January 1984, 116 patients with advanced non-small-cell carcinoma of the lung (NSCCL) were randomly assigned to 3 combinations as follows: CDDP + DVA, CDDP + VP16 and DXR + CTX. 94 patients were evaluable for response, 106 for toxicity and survival. Of 31 patients, 15 (48%; 3 CRs and 12 PRs) responded to CDDP + DVA; of 33 patients, 12 (36%, 2 CRs and 10 PRs) responded to CDDP + VP16; of 30 patients, 3 (10%) obtained a PR with DXR + CTX (CDDP + DVA vs DXR + CTX, P less than 0.005; CDDP + VP16 vs DXR + CTX, P less than 0.05; CDDP + DVA vs CDDP + VP16, P = NS). The median duration of response was 22 weeks in the CDDP-DVA group, 17 weeks in the CDDP-VP16 group, and 16 weeks in the DXR + CTX group. No significant difference in survival was observed among the 3 groups (median: 43, 47, 41 weeks, respectively). Hematologic and neurologic toxicities were significantly higher in the DVA-containing regimen. Despite the lack of improvement of overall survival with the CDDP-containing combinations over the DXR + CTX control group, the good response rate makes them suitable to be used in combined therapeutic strategies.

Adult↗

Localized ovarian cancer: surgery plus chemotherapy.

Fifty-four patients were referred to Medical Oncology after operation for "limited" ovarian cancer; 7 were excluded because immediate restaging showed evidence of macroscopic spread to structures outside the true pelvis, and 10 will be considered separately because of microscopic spread shown only by cytology. Thirty-seven patients (31 stage I and 6 stage II) were accordingly accepted as "localized", because peritoneal cytology and diaphragm and omental plus parietal peritoneum histology could rule out the spread to the large abdominal cavity. Some of the referred patients had been operated in nearby hospitals; the Padua GYN Cin. performed 14 of the 37 first surgery operations and 30 of the 37 second look operations. All patients soon after surgery underwent first-line chemotherapy with 5 courses of high dose adriamycin plus cyclophosphamide for 4 months, then surgical second look, and second-line non-cross-resistant chemotherapy for 3 months. During the second look the organ and tissue removal was completed in those 21 patients having received "limited" first surgery. Two patients died within 5 years from admission, so that the overall 5 year actuarial survival from referral is 93% for the entire group with 11 patients still at risk; 87% are disease free 5 years after the second look with 7 at risk. Subdivision of the patients according to "adequate" vs. "limited" first surgery, may select a group (the "adequate" one, composed of 16 patients) completely free from relapses, up to now. The complex therapeutic program described seems to offer long term relapse-free survival to the majority of patients, while the few failures seem closely related with inadequacies of the initial surgical procedure.

Adolescent↗

Phase II evaluation of 4'epi-doxorubicin in patients with metastatic colorectal carcinoma.

Thirty-four evaluable patients with metastatic colorectal carcinoma (13 rectal primary and 21 colonic primary, 4 pretreated and 30 untreated) received 4'epi-doxorubicin at the dose of 75 mg/m2 i.v. once every 21 days, for a minimum of 2 courses. Symptomatic toxicity (mainly confined to gastrointestinal complaints) was short-lived and easily managed. Hematologic toxicity was mild. Transient electrocardiographic abnormalities were found in 50% of patients, without signs of significant cumulative cardiotoxicity. Three previously untreated patients achieved a partial response (lasting 16, 12 and 12 weeks, respectively) with a response rate of 9% (3%-23%, 95% confidence interval). More interestingly, all responsive patients had rectal cancer: further studies of 4'epi-doxorubicin confined to the rectal localization seem warranted.

Adult↗

Vindesine in the treatment of squamous cell carcinoma (WHO I), adenocarcinoma (WHO III), and large cell carcinoma (WHO IV) of the lung.

The antineoplastic activity of vindesine was evaluated in 57 patients with non-small-cell carcinoma of the lung, 53 patients were fully evaluable for response and toxicity. Twenty-seven patients had squamous cell carcinoma (WHO I), 14 had adenocarcinoma (WHO III), and 12 had large cell carcinoma (WHO IV). Forty percent of patients were previously treated. Vindesine was administered at a weekly i.v. dose of 3 mg/m2. Partial remissions were observed in 2 of 12 patients with large cell carcinoma and in 1 of 27 patients with squamous cell carcinoma. Among 14 patients with adenocarcinoma, 3 minor responses were observed. Drug-related toxic effects (mainly leukopenia with manageable and reversible neurotoxicity) required modification of dose in 41% of patients: this finding and previous treatment may have adversely affected the response rate. It is concluded that vindesine as a single agent has some activity in large cell carcinoma. Activity in the other histologic types was minimal but not totally absent and deserves further evaluation, possibly in non-pretreated patients.

Adenocarcinoma↗

Phase II study of 4'epi-doxorubicin.

Sixty-five patients with advanced solid tumors were treated with 4'epi-doxorubicin, a new analogue of doxorubicin (DXR). Forty-three of 61 evaluable patients had not received previous chemotherapy and/or hormonal treatment. 4'Epi-doxorubicin has been administered at the dose of 75 mg/m2 i.v. once every 21 days, for a minimum of 2 courses. The pattern of acute toxicity was similar to that of DXR. Transient electrocardiographic abnormalities were found in about 50% of patients. The ratio of pre-ejection period to the left ventricular ejection time (PEP/LVET) increased within 1 h after drug injection and returned to near basal values after 24 h. Three patients received a total dose of more than 550 mg/m2, still maintaining a baseline PEP/LVET ratio near to pretreatment values. Up to now, no patient has developed clinical signs of heart failure. Partial responses were seen in patients with tumors generally sensitive to DXR such as breast carcinoma (6 of 14) and soft tissue sarcomas (2 of 6), and in patients with tumors generally resistant to DXR such as melanoma (1 of 9), colorectal carcinoma (3 of 18) and pancreatic carcinoma (1 of 2). These data suggest that 4'epi-doxorubicin may have a broader spectrum of antitumor activity than DXR.

Adult↗

Phase II evaluation of vindesine in mycosis fungoides, extraosseous plasmacytoma and other hematologic malignancies.

We conducted a phase II trial of Vindesine in 24 patients, mostly pretreated (23/24 fully evaluable for therapeutic response) with advanced hematologic malignancies. The drug was administered at weekly bolus doses of 3 mg/m2 i.v. Overall, objective tumor regressions were seen in 9 of 23 patients. The drug appeared effective in extraosseous plasmacytoma (1 complete response, 1 partial response and 1 minor response in 6 patients). Further phase II trials in these 2 diseases are justified. In addition, 3 partial responses in 7 patients with advanced lymphoma were also obtained. Previous vinca-alkaloid exposure did not adversely affect the response rate: 8 of 9 responsive patients had previously received vincristine and/or vinblastine. Drug-related toxic effects were mainly represented by manageable and reversible neurotoxicity and by moderate leukopenia with apparent lack of thrombocytopenia. In heavily pretreated patients, leukopenia may be occasionally severe: in these conditions a starting dose of 2 mg/m2 seems more appropriate.

Adult↗

False positive bone scan in bone tumors of the lower limb.

When examined using bone scanning agents, eight out of nine patients with lower limb malignancy, and neither of two affected in the upper limb showed a pathologic focus of isotope uptake in an area distal to the tumor. On pathologic examination the positive findings proved false. Such misleading results were found to be avoidable if a tumor-seeking agent instead of a bone scanning one is used.

Adolescent↗

Conditioned medium from MCF-7 cell line induces myofibroblast differentiation, decreased cell proliferation, and increased apoptosis in cultured normal fibroblasts but not in fibroblasts from malignant breast tissue.

We studied the effect of conditioned medium (CM) obtained from cultures of oestrogen-receptor positive breast cancer MCF7 cell line on the differentiation, proliferation and apoptosis patterns of cultured breast fibroblasts from normal interstitial and malignant stromal tissue. Fibroblasts were grown in the presence or absence of CM and examined for the differentiation pattern by immunofluorescence and Western blotting procedures, for proliferation profile by Ki67 expression, and for apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling technique. Monoclonal antibodies specific for non-muscle (NM), smooth muscle (SM) lineage and differentiation markers were applied to these cultures. CM is able to induce a SM-like differentiation in interstitial fibroblasts, i.e., essentially myofibroblast formation. Fibroblasts from tumour stroma showed the presence of a small number of smooth muscle cells (SMC) along with a large number of myofibroblasts. Treatment of these cultures with CM was unable to change this pattern. Only normal fibroblasts were responsive to the proliferation/apoptotic-inhibitory effect of the CM. These data suggest that structural and functional differences exist between stromal fibroblasts from normal breast and breast cancer with respect to the responsiveness to soluble factors present in the CM. We hypothesize that the lack of in vitro sensitivity to CM shown by 'tumour' fibroblasts is the result of an in vivo inherent and stable phenotypic change on the fibroblasts surrounding breast tumour cells occurring via a paracrine mechanism.

Apoptosis↗

A new nested primer pair improves the specificity of CK-19 mRNA detection by RT-PCR in occult breast cancer cells.

Reverse transcription polymerase chain reaction (RT-PCR) of cytokeratin-19 (CK-19) has been widely used to detect small numbers of circulating malignant epithelial cells in the bone marrow or the peripheral blood of patients with breast cancer. However, a high percentage of false positive results has been recorded and conflicting reports question the clinical relevance of this technical approach. We demonstrate that the use of a new nested primer pair for CK-19 RT-PCR avoids false positive results without affecting the sensitivity of the assay. Our experiments were carried out using MCF-7 cells alone or mixed with peripheral blood mononuclear cells (PBMNC) of healthy donors. The results were also validated in a large series of healthy donors and in a preliminary study on a limited number of patients with breast cancer, thus suggesting that our assay is feasible for application in the clinical evaluation of occult malignant epithelial cells.

Adult↗

Quantitative chemiluminescent immunoassay of p53: prognostic significance in 220 node-negative breast cancer tissue.

The prognostic and predictive role of p53 overexpression in breast cancer samples is usually investigated by using molecular biology or immunohistochemical methods. However, the results are to date controversial, and this is in part due to the methodological pitfalls of both the methods. To study the possibility of overcoming, at least in part, these problems we evaluated a commercially available chemiluminescent immunoassay with which the p53 concentrations of 220 specimens from node negative breast cancer were determined. The assay showed good analytical performance and found detectable levels in 84.7% of cases (median 0.22 ng/mg of proteins, range 0-50 ng/mg of proteins). p53 has been found inversely correlated with estrogen receptors and directly correlated with cathepsin D. The prognostic role of p53 was evaluated in two different ways: a) two previous studies (Borg et al 1995, DeWitte et al. 1996) using the same method found almost 30% of samples had significantly shorter DFS and OS. We subdivided our cases in order to identify the same positivity rate and to verify if the previous cathegorizations were effective also in our patient series. We confirmed the independent association with DFS (p = 0.006) and OS (p = 0.0005); b) considering that any categorization of quantitative parameters could cause a loss of clinical information, we also evaluated p53 as a continuous variable. Multivariate analysis showed a significant quantitative relationship between p53 and both disease free (p = 0.026) and overall survival (p = 0.02).

Aged↗