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S Graziano

Publications and source records attributed to S Graziano.

15 recordsLinked to original sources
PubMed1992

Acute leukemia arising from a myelodysplastic syndrome after long-term administration of iproplatin.

BACKGROUND: Iproplatin (cis-dichloro-transdihydroxybis-isopropylamine platinum IV; CHIP) is a second generation cisplatin derivative that was developed to retain the antineoplastic effect of cisplatin with fewer toxic effects. Early clinical studies showed moderate activity in some neoplasms, with disappointing results in tumors of the lower gastrointestinal tract. Myelosuppression was the dose-limiting toxic effect in the acute setting. METHODS: The authors report a patient with metastatic adenocarcinoma of the colon who received long-term therapy with CHIP. RESULTS: The patient achieved complete remission of disease after prolonged treatment with CHIP. The patient subsequently had a myelodysplastic syndrome that rapidly transformed to acute myelogenous leukemia. CONCLUSIONS: Acute leukemia may represent a late complication of CHIP therapy.

Adenocarcinoma↗
PubMed1992

Hypersensitivity reactions to procarbazine with mechlorethamine, vincristine, and procarbazine chemotherapy in the treatment of glioma.

The authors report the clinical features of hypersensitivity reactions believed to result from procarbazine in eight patients treated with mechlorethamine, vincristine, and procarbazine (MOP) for high-grade glioma. There was one instance of hypersensitivity in 7 patients treated for recurrent disease and seven instances in 16 patients treated with an adjuvant protocol using MOP directly after surgery. Maculopapular rash was seen in seven of eight, fever was seen in four of eight, and reversible abnormal liver function test results were seen in three of four patients. Pulmonary toxic effects were seen in five of eight patients and consisted of isolated interstitial pneumonitis in one, fever and infiltrate after rechallenge with procarbazine after previous rash in two, and cough accompanying rash in two. The toxic effects were mild to moderate in six patients but severe to life threatening in the two who were rechallenged after development of rash. The observed incidence of rash during adjuvant therapy was higher than that previously found by the authors for recurrent disease, and it appears to be higher than has been reported in Hodgkin's disease, lymphoma, and other solid tumors. The findings by the authors suggest that a high index of suspicion be kept for hypersensitivity reactions to procarbazine when treating primary brain tumors and that, contrary to the experience in other settings, procarbazine be stopped if rash develops.

Aged↗
PubMed1992

Safety and cost effectiveness of high-osmolality as compared with low-osmolality contrast material in patients undergoing cardiac angiography.

BACKGROUND AND METHODS: Low-osmolality contrast agents produce fewer hemodynamic and electrophysiologic alterations during cardiac angiography, but they are 20 times more expensive than high-osmolality contrast agents. In a randomized, double-blind trial comparing a nonionic low-osmolality contrast agent (Omnipaque 350) with a high-osmolality agent that does not avidly bind calcium (Hypaque 76) in 505 patients undergoing cardiac angiography, we determined the incidence of minor, mild, moderate, and severe adverse reactions, identified risk factors for such reactions, and evaluated the cost effectiveness of various strategies for the use of contrast material. RESULTS: The 253 patients who received a high-osmolality contrast agent were three times more likely to have a moderate adverse reaction (95 percent confidence interval for the relative risk, 1.6 to 5.5) but no more likely to have a severe reaction (95 percent confidence interval, 0.2 to 2.3) than the 252 patients who received a low-osmolality agent. All 10 severe reactions occurred in patients who were older than 60 years or had unstable angina. Patients with these characteristics were also 3.5 times more likely (95 percent confidence interval, 1.8 to 6.8) to have a moderate reaction (44 of 310 patients, or 14 percent) than those without either characteristic (8 of 195 patients, or 4 percent). We estimated that the incremental cost of each moderate reaction avoided would be $1,698 with a strategy that involved giving a low-osmolality contrast agent only to patients who were over 60 years of age or had unstable angina, instead of giving a high-osmolality agent to all patients. The incremental cost per moderate reaction avoided by giving a low-osmolality contrast agent to all patients rather than only to those over 60 or with unstable angina would be $5,842. CONCLUSIONS: The use of contrast agents with low rather than high osmolality during cardiac angiography reduces the risk of moderate, but not of severe, adverse reactions to the agent used. A strategy of reserving low-osmolality contrast agents for use in patients at high risk for adverse reactions would be more cost effective than one requiring their use in all patients.

Age Factors↗
PubMed1992

Nephrotoxicity of high-osmolality versus low-osmolality contrast media: randomized clinical trial.

The comparative frequency of and risk factors for nephrotoxicity with low-osmolality contrast medium (LOM) versus high-osmolality contrast medium (HOM) were investigated. A randomized, double-blind clinical trial was conducted in patients undergoing diagnostic angiocardiography (n = 430) or contrast material-enhanced body computed tomography (CT) (n = 499). Nephrotoxicity was defined as an increase in serum creatinine level that was greater than both 33% and 0.4 mg/dL (40 mumols/L) above the baseline level within 48 hours after the radiologic procedure. The frequency of nephrotoxicity was similar in patients who received LOM versus those who received HOM: 13 of 479 (2.7%) versus 13 of 450 (2.9%), respectively (P = .87), overall; 4.4% versus 4.0% in angiocardiography patients (P = .84); and 1.2% versus 2.0% in body CT patients (P = .35). Factors associated (P less than .05) with increased risk of nephrotoxicity were insulin-dependent diabetes, baseline serum creatinine level greater than 1.5 mg/dL (130 mumols/L), concurrent use of furosemide, and angiocardiographic examination. Patients who have preexisting renal insufficiency may be at higher risk for nephrotoxicity with HOM than with LOM.

Angiocardiography↗
PubMed1991

Carboplatin and vinblastine in advanced non-small-cell lung cancer: a phase II study.

Between July 2, 1987, and August 21, 1987, Cancer and Leukemia Group B (CALGB) conducted a phase II evaluation of carboplatin (CBDCA) and vinblastine (VBL) in advanced non-small-cell lung cancer. Of the 58 patients who entered the study, 55 were eligible and produced follow-up data. Chemotherapy, which was carried out in 28-day cycles, consisted of 4 mg/m2 VBL given on days 1 and 3 and 125 mg/m2 CBDCA given on days 1-3. Partial responses were observed in 10 cases (18%), and 1 patient (2%) exhibited regression of evaluable disease. No complete responses were achieved. The overall objective response rate was 20%. The median survival was 6.1 months, and the median time to treatment failure was 3.3 months. Life-threatening (grade 4) toxicity was mainly leukopenia (20%), followed by anemia (7%), infection (4%), thrombocytopenia (2%), fever (2%), nausea and vomiting (2%), and weight loss (2%). There were two deaths due to infection. The results of this study demonstrate that the combination CBDCA/VBL is active in advanced NSCLC; however, whether this combination is more active than either CBDCA or VBL alone is unknown.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Molecular mapping of deletion sites in the short arm of chromosome 3 in human lung cancer.

We used 10 restriction fragment length polymorphism (RFLP) probes spanning the length of the short arm of chromosome 3 (3p) to map deletion sites in human lung cancer. Two approaches were used. 1) When a patient's tumor and normal tissue were available, loci with allelic heterozygosity in the normal tissue were tested for loss of alleles at 3p. 2) When the corresponding normal tissue was not available, the frequency of heterozygosity at each locus in a panel of tumors was compared to the corresponding published frequencies in nontumor tissue of healthy individuals or patients with lung cancer. In 14 small cell lung carcinomas (SCLC) with normal DNA for comparison, allele loss was found at all heterozygous loci, with one exception at a locus near the 3p centromere (D3S4). In the total of 53 SCLCs, which included tumors without paired normal tissue, frequency of heterozygosity was significantly reduced in all 10 3p loci. Three loci, DNF 15S2, RAF1, and D3S18, were homozygous in all tumors in the SCLC panel. These loci, which are in regions 3p21 and 3p25, may thus be involved in the origin or evolution of SCLC. We also investigated 24 non-SCLC tumors. In this panel, frequency of heterozygosity was significantly reduced at seven of the 10 loci tested. Comparison of the results shows that the pattern of allele loss on 3p is different in SCLC and non-SCLC, suggesting a difference in pathogenesis at the genetic level.

Alleles↗
PubMed1990

Carboplatin in malignant mesothelioma: a phase II study of the Cancer and Leukemia Group B.

Carboplatin (400 mg/m2) was given at 28-day intervals to 41 patients with malignant mesothelioma. In all, 40 patients were eligible and evaluable for response. Partial responses were seen in 2 cases (5%); regression of evaluable disease, in 1 patient (2%); and stable disease, in 19 subjects (48%). A median of two doses of carboplatin per patient resulted in mild toxicity. Leukopenia (less than or equal to 2,000 cells/microliters) and thrombocytopenia (less than 100,000 cells/microliters) were seen in only 6% and 20% of the patients, respectively. Median survival from study entry was estimated at 7.1 months, with a 1-year survival of 25% +/- 7%. Carboplatin given at a dose of 400 mg/m2 at 28-day intervals shows minor activity against malignant mesothelioma.

Adult↗
PubMed1990

Integrating technology assessment and medical practice evaluation into hospital operations.

The Johns Hopkins Program for Medical Technology and Practice Assessment, established in 1986, assesses the clinical efficacy, safety, and cost of specific technologies; evaluates the costs and benefits of alternative approaches to management of clinical problems; and examines the clinical and economic impact of health care program innovations. For example, program faculty have conducted analyses of clinical economic, and health policy issues related to radiographic contrast media. The director of the program chairs a committee that formulates guidelines for the appropriate use of low-osmolality contrast media and that will develop a mechanism to ensure compliance with guidelines. Program faculty are currently studying variations in the pre-, intra-, and postoperative management of patients with cataract and the relationship between such variations and outcomes. Faculty are also attempting to develop an improved mechanism for paying health maintenance organizations that enroll Medicare beneficiaries. Program activities have had a direct impact on decision making within the Johns Hopkins Health System.

Baltimore↗
PubMed1990

Mechlorethamine, vincristine, and procarbazine chemotherapy for recurrent high-grade glioma in adults: a phase II study.

We undertook a phase II study of combination chemotherapy with mechlorethamine (nitrogen mustard) 6 mg/m2 intravenously day 1 and day 8, vincristine 2 mg intravenously day 1 and day 8, and procarbazine 100 mg/m2 orally days 1 through 14 (MOP) in adults with recurrent high-grade glioma. There were 31 patients entered and 27 patients assessable for response. The median age was 49 years old. All patients had prior maximal radiotherapy, and eight had previous chemotherapy. Responses were determined based on clinical and computed tomographic (CT) scan/magnetic resonance imaging (MRI) criteria. The response rate (partial response [PR] plus objective qualitative response [OQR] plus complete response [CR]) was 52% with one CR. The response rate was higher in patients with anaplastic astrocytoma as compared with glioblastoma multiforme (P less than .05). The median duration of response was 42 weeks. Median survival for all assessable patients was 30 weeks, and for responders, it was 60 weeks. Response was correlated with ability to decrease dexamethasone doses and improved performance status. Toxicity was mainly hematologic with leukopenia being common. There was one treatment-related death from listeria meningitis, and two patients developed Pneumocystis carinii pneumonia. There were three episodes of neutropenic fever. We conclude that MOP is active and merits further investigation in adult high-grade glioma.

Adult↗
PubMed1989

Cooperation of c-raf-1 and c-myc protooncogenes in the neoplastic transformation of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells.

Overexpression of c-raf-1 and the myc family of protooncogenes is primarily associated with small cell carcinoma, which accounts for approximately 25% of human lung cancer. To determine the functional significance of the c-raf-1 and/or c-myc gene expression in lung carcinogenesis and to delineate the relationship between protooncogene expression and tumor phenotype, we introduced both protooncogenes, alone or in combination, into human bronchial epithelial cells. Two retroviral recombinants, pZip-raf and pZip-myc, containing the complete coding sequences of the human c-raf-1 and murine c-myc genes, respectively, were constructed and transfected into simian virus 40 large tumor antigen-immortalized bronchial epithelial cells (BEAS-2B); this was followed by selection for G418 resistance. BEAS-2B cells expressing both the transfected c-raf-1 and c-myc sequences formed large cell carcinomas in athymic nude mice with a latency of 4-21 weeks, whereas either pZip-raf- or pZip-myc-transfected cells were nontumorigenic after 12 months. Cell lines established from tumors (designated RMT) revealed the presence of the cotransfected c-raf-1 and c-myc sequences and expressed morphological, chromosomal, and isoenzyme markers, which identified BEAS-2B cells as the progenitor line of the tumors. A significant increase in the mRNA levels of neuron-specific enolase was detected in BEAS-2B cells containing both the c-raf-1 and c-myc genes and derived tumor cell lines. The data demonstrate that the concomitant expression of the c-raf and c-myc protooncogenes causes neoplastic transformation of human bronchial epithelial cells resulting in large cell carcinomas with certain neuroendocrine markers. The presented model system should be useful in studies of molecular events involved in multistage lung carcinogenesis.

Animals↗
PubMed1988

Phase II trial of 4'-deoxydoxorubicin (DxDx) in non-small cell lung cancer: a Cancer and Leukemia Group B Trial.

Eighty-seven patients with histologically or cytologically proven non-small-cell carcinoma of the lung were treated with 4'-deoxydoxorubicin (DxDx) 30 mg/m2 every 3 weeks. Three responses (4%), all partial, were observed. All responses occurred in patients with large-cell anaplastic lung cancer and none in squamous or adenocarcinoma histologies (P less than 0.01). The durations of partial response for these three responders were 70, 198+ and 209+ days. The side effects noted were predominantly neutropenia, anemia, and weight loss. In three patients, declines in cardiac ejection fraction of 7%, 12%, and 23% occurred after cumulative drug doses of 150 mg/m2, 150 mg/m2, and 233 mg/m2, respectively. 4'-Deoxydoxorubicin had little activity in non-small-cell lung cancer at the dose used in this study.

Carcinoma, Non-Small-Cell Lung↗
PubMed1987

Molecular analysis of the short arm of chromosome 3 in small-cell and non-small-cell carcinoma of the lung.

Previous studies have suggested that the loss of DNA sequences on the short arm of chromosome 3 (3p) is associated with small-cell lung carcinoma. We therefore looked for loss of 3p alleles in tumor tissue from 42 patients with either small-cell or non-small-cell lung carcinoma. All 13 patients with small-cell lung carcinoma who were heterozygous for one or more alleles at 3p in normal tissue had the loss of at least one codominant allele in the tumor tissue. Cell lines of small-cell lung carcinoma from an additional eight patients were homozygous for 3p alleles; this result was significantly different from the predicted frequency of homozygosity. The tumor tissue studied included cell lines of small-cell lung carcinoma obtained from biopsy specimens, an autopsy sample, and an excised lymph node containing tumor cells. Loss of alleles at 3p was observed in tumor samples obtained before and after chemotherapy. Four of 15 evaluable patients with non-small-cell carcinoma of the lung had loss of 3p alleles. We conclude that loss of alleles at 3p is a change found consistently in small-cell lung carcinoma and occasionally in non-small-cell lung carcinoma.

Alleles↗
PubMed1987

Carboplatin or iproplatin in advanced non-small cell lung cancer: a Cancer and Leukemia Group B Study.

The effect of the cisplatin analogs carboplatin (CBDCA) or iproplatin (CHIP) was evaluated in patients with extensive non-small cell lung cancer. The randomized phase II design was used to achieve balance between patient groups and comparison of response rates was not a primary objective of the study. CBDCA (400 mg/m2 iv) or CHIP (270 mg/m2 iv) was administered every 4 weeks until relapse of disease. Overall, 11 of 70 patients (16%; 95% confidence interval: 7%-25%) responded to CBDCA and five of 71 patients (7%; 95% confidence interval: 1%-13%) responded to CHIP. There were two complete responses to CHIP and none to CBDCA. The most frequent severe or life-threatening toxic effects were thrombocytopenia and leukopenia. Median survival for patients receiving CBDCA was 6.5 months; for those on CHIP it was 5.0 months (P = 0.59). CBDCA is probably active in patients with non-small cell lung cancer whereas CHIP has limited activity. Further evaluation of CBDCA as part of combination chemotherapy for non-small cell lung cancer is warranted.

Adult↗