Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of cis-diamminedichloroplatinum (CDDP) was studied in 21 patients with intracerebral metastatic brain tumors from lung cancer after CDDP 100 mg/sq m i.v. or i.a. administration for 20 minutes using an infusion pump during surgery. Surgical tissue specimens of tumor and edematous brain tissue adjacent to tumor were obtained with whole blood soon after CDDP administration and assayed for total platinum using an atomic absorption spectrophotometer. The pharmacological distribution rates were represented as the brain/plasma, tumor/plasma and tumor/brain ratios. No statistical differences in the CDDP concentrations in the plasma were found between i.a. and i.v. administrations. The platinum concentration in edematous brain tissue adjacent to the tumor was always lower than the platinum concentration in the metastatic intracerebral tumor. No differences were noted for the brain/plasma ratio in the brain tissue adjacent to the tumor between the two administration methods (i.a.: 0.38 +/- 0.09, n = 8; i.v.: 0.43 +/- 0.13, n = 11, M +/- S.E.). However, two cases who each underwent two different administration courses showed i.a. to be pharmacologically advantageous since it resulted in a 2-to-7 times higher concentration in the brain tissue adjacent to the tumor. The tumor/plasma and tumor/brain ratios for i.a. administration (1.72 +/- 0.26, 6.09 +/- 1.30, n = 8, M +/- S.E.) were two times higher than those for i.v. administration 0.90 +/- 0.23, n = 12, 3.40 = 0.59, n = 10, M +/- S.E. (p less than 0.05, p = 0.061, unpaired t-test). Toxic side effects were moderate, especially decreased creatinine clearance, but tolerable. Our preliminary results demonstrated the pharmacologic advantage of i.a. CDDP chemotherapy in the treatment of metastatic brain tumor patients.
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PMID:[Distribution of cis-diamminedichloroplatinum in patients with metastatic brain tumors after intravenous or intracarotid administration]. 198 91

cis-Diamminedichloroplatinum(II) (CDDP) was given as a single agent at a dose of 25 mg/m2 daily for 5 days by continuous infusion; treatment was repeated every 4 weeks in 30 previously untreated patients with advanced non-small-cell lung cancer (NSCLC). The median age of the patients was 61 years; 13 patients had limited disease and 17, extensive disease. The overall response rate was 40% (12/30; 95% confidence limits, 23-58%), with a median survival of 8 months. Vomiting was observed in 37% of patients; elevated serum creatinine levels (greater than 1.5 mg/dl), in 7%; leukopenia (less than 3,000/mm3), in 39%; thrombocytopenia (less than 70,000/mm3), in 26%; and anemia (hemoglobin less than 9.5 g/dl), in 60% of patients. In all cases, these toxicities were mild and transient, requiring no dose modification. The exposure to filterable platinum, determined from the area under the concentration-time curve, was 9.08 +/- 3.21 micrograms h ml-1. We conclude that CDDP given by 5-day continuous i.v. infusion is safe and effective for treatment of NSCLC.
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PMID:Phase II study of 5-day continuous infusion of cis-diamminedichloroplatinum(II) in the treatment of non-small-cell lung cancer. 217 93

In order to detect even subclinical hints of nephrotoxicity after application of carboplatin, sensitive non-invasive methods, e.g. determination of urinary enzyme (lactate dehydrogenase, leucine aminopeptidase, gamma-glutamyltransferase, N-acetyl-beta-glucosaminidase), glomerular and tubular protein excretion (albumin, alpha-1-microglobulin) and determination of the creatinine clearance, were used. Eighteen patients with small-cell lung cancer entered the study. All patients were treated with the three-drug combination chemotherapy: vincristine (1.5 mg i.v. on days 1, 8, 15, 22), etopside (escalating doses: 100-160 mg/m2 on days 1-3) and carboplatin (300 mg/m2 day 1). Investigations were made during the first, third and fifth treatment cycles. Deterioration of renal function occurred in 4 out of 18 patients in all three observed treatment courses. Abnormal amounts in the excretion of at least one of four urinary enzymes were found in 6 out of 18 patients during the first cycle and in 4 out of 8 patients during the third and fifth cycles. All patients with pathological enzymuria during the first treatment course also developed an increased enzymuria during cycles 3 and 5. Four patients developed pathological proteinuria during the first and 2 patients during the third and fifth cycles. These findings demonstrate that the new platinum analogue, carboplatin, is capable of inducing renal damage. In comparison with cisplatinum, the nephrotoxicity of this new analogue is reduced but not completely eliminated.
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PMID:Investigations on the acute and chronic nephrotoxicity of the new platinum analogue carboplatin. 218 39

A multi-institutional prospective study for the analysis of prognostic factors for patients with osseous metastasis was performed. From February 1986 through June 1988, a total of 216 patients were included in this study. Cox's regression model made it clear that the most significant overall prognostic factor was primary site (p = 0.0002). In the lung cancer group, performance status (p = 0.0036) and metastasis of organs than bone (p = 0.0105) were also significant prognostic factors. In the breast cancer group, no significant factors were obtained. In the hepatoma group, the values for alkaline phosphatase (ALP) (p = 0.0021), lactate dehydrogenase (LDH) (p = 0.0195), and sex (p = 0.0264) proved significant. In the group of other cases, the most significant prognostic factor was the value for urinary hydroxyproline/creatinine ratio (p = 0.0001), followed by the pain score of RTOG (p = 0.0018). These factors and actual survival periods obtained in this study will be useful for the future stratification of patients for individualized optimal radiation schedules.
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PMID:Prognostic factors for patients with osseous metastasis: a multi-institutional prospective study. 219 3

This phase I study was carried out to determine the maximal tolerated dose of carboplatin (Car) together with a fixed dose of etoposide (E) and to recommend the optimal dose for a phase II study. The dose of E was 100 mg/m2 given i.v. on days 1-3, and the starting dose of Car was 200 mg/m2 given i.v. on day 1. The dose was escalated until WHO grade 4 toxicity developed after two treatment cycles in more than one-third of the patients. A total of 33 patients with advanced lung cancer entered the trial. The maximal tolerated toxicity of the combination was reached at a dose of 500 mg/m2 Car. Myelosuppression was moderate, and hematological toxicity of WHO grade 4 was encountered in one of five patients at 475 mg/m2 and in two out of five patients at 500 mg/m2. The main toxic effects were leucopenia and thrombocytopenia. The frequency of treatment-related infections was low and no deaths were caused by treatment. There was a significant overall correlation between the platelet nadir and creatinine clearance. One complete response and three partial responses were achieved after two treatment cycles. Based on the results of the present study, the dose of carboplatin (combined with 100 mg/m2 eposide given on days 1-3) recommended for phase II studies is 450 mg/m2.
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PMID:Carboplatin and etoposide in advanced lung cancer:--a phase I study. 226 60

Urinary levels of immunoreactive (IR) human NH2-terminal (hNT) of pro-opiomelanocortin were measured in 43 patients with various cell types of lung cancer (19 squamous cells, 12 oat cells, 2 large cells, and 10 adenocarcinoma), 32 patients with benign lung disease, two patients after hypophysectomy, and in 23 healthy volunteers. Lung cancer patients were divided into two subgroups according to the stage of the disease: 22 patients had "limited", and 21 patients "extensive" disease. Urinary and plasma levels were measured in 9 patients with lung cancer before and after radio- and chemotherapy or surgery. Urine samples were dialyzed and IR hNT material was extracted by Sep Pak C-18 cartridges using a propanol-2/TFA solvent system. The plasma and urinary IR hNT levels of the normal controls were 124 +/- 25 pg/ml and 47.8 +/- 14.5 pg/mg creatinine, respectively. The plasma levels of IR hNT were elevated (greater than mean + 2SD) in 65% of our patients with histologically proven lung cancer (422 +/- 775, mean +/- SD, pg/ml). The highest incidence of an elevated plasma level of IR hNT was found in oat cell carcinoma (83%). Elevated plasma IR hNT occurred in 66% of the patients with benign pulmonary disease (246 +/- 141 pg/ml, N.S.). In cancer patients with "limited" disease we found levels of 226 +/- 143 pg/ml and in patients with "extensive" disease 627 +/- 1074 pg/ml (N.S.). The urinary IR hNT level in lung cancer patients was 186 +/- 337 pg/mg creatinine and 81% of our patients had elevated levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urinary levels of immunoreactive NH2-terminal of pro-opiomelanocortin in patients with malignant pulmonary disease. 253 37

The authors investigated the reductive effects of a Kunitz-type proteinase inhibitor, urinastatin, on the nephrotoxicity seen in lung cancer patients treated with cisplatin by measuring N-acetyl-beta-D-glucosaminidase (NAG) activity and beta 2-microglobulin (BMG) content in 24 hour urine, creatinine clearance, blood urea nitrogen (BUN), serum creatinine, uric acid, and BMG as factors of nephrotoxicity. In control patients treated with anticancer drugs containing cisplatin but no supplemental urinastatin, the 24 hour urine NAG and BMG levels increased more than three-fold over the pretreatment levels, 3 days after anticancer therapy, respectively. Creatinine clearance significantly decreased and levels of BUN, serum uric acid, and BMG in control patients significantly increased over the corresponding pretreatment levels, 3 days after anticancer therapy. However, supplemental urinastatin reduced abnormalities in levels of all these factors 3 days after therapy. These results suggest that supplemental urinastatin protects from cisplatin-induced nephrotoxicity, especially proximal tubular damage.
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PMID:Urinastatin (Kunitz-type proteinase inhibitor) reducing cisplatin nephrotoxicity. 255 2

The effect of pretreatment with bismuth subnitrate (BSN) for prevention of the renal toxicity of cisplatin (CDDP) was examined in 44 patients with lung cancer (43 non-small cell and one small cell lung cancer). In non-small cell lung cancer cases, the effect of the antitumor activity of chemotherapeutic drugs was observed in 62% of patients pretreated with BSN, and 42% in the group without pretreatment with BSN. No antitumoral activity of chemotherapeutic drugs was suppressed by treatment with BSN. In the group without pretreatment of BSN, serum creatinine and BUN were in proportion to the number of administrations of chemotherapeutic drugs. On the other hand, no renal toxicity was shown in the group with pretreatment by BSN. No protective effect against myelosuppression with pretreatment by BSN was demonstrated, perhaps because of the influence of anti-cancer drugs apart from CDDP.
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PMID:[Prevention of renal toxicity of cisplatin by administration of bismuth subnitrate]. 255 15

Thrombocytopenia, the dose-limiting toxicity of carboplatin, is manageable and predictable with the dosing equation: Dose (mg/m2) = (0.091) (creatinine clearance)/(body surface area) (desired percentage change in platelet count) + 86. We used this equation to dose patients receiving carboplatin (day 1) and etoposide (80 mg/m2 days 1 to 3). An initial cohort of 14 patients with non-small-cell lung cancer (NSCLC) were treated with 75% of the calculated dose of carboplatin (29 evaluable courses) as a precaution against added myelosuppression from combination chemotherapy. The observed reduction in platelets was essentially equal to the reduction in platelets predicted if patients had received carboplatin alone. Subsequently, a second cohort of 20 evaluable patients with NSCLC received the full calculated dose of carboplatin and etoposide (51 evaluable courses). There was a linear relationship between observed (o) and predicted (p) reductions in platelets. With full-dose carboplatin in combination with etoposide, there was a significantly greater carboplatin dosage administered, greater reduction in platelets, and lower platelet nadir. Among 34 evaluable patients (80 courses) there was one complete response (CR) and four partial responses (PRs) for an overall response rate of 15% (90% confidence +/- 9%). The median duration of survival for responders was 336+ days and for nonresponders was 204+ days. Therapy was well tolerated. This study, in addition, supports our concept of individualized dosing of carboplatin and the underlying pharmacokinetic/pharmacodynamic relationships and represents an interesting pharmacodynamic and quantitative approach to studying potential drug-drug interactions and defining appropriate dosages for combination chemotherapy.
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PMID:A novel pharmacodynamically based approach to dose optimization of carboplatin when used in combination with etoposide. 169 37

Eleven aged patients over 65 years of age with advanced lung cancer (mean age = 70.8 +/- 1.4, non-small cell:small cell = 9:2, stage III:IV = 5:6) were treated with combination chemotherapy consisting of cisplatin (50 or 80 mg/m2) and vincaloids (vindesine 3 mg/m2 or etoposide 80 mg/m2). To evaluate this cisplatin combination therapy, the aged group was compared with a young group consisting of eleven patients (mean age = 53.3 +/- 1.7, non-small cell:small cell = 9:2, stage III:IV = 5:6) matched for cell type, stage and dose regimen. The mean dose of cisplatin was 58.2 mg/m2 in the aged and 63.6 mg/m2 in the younger group. A notable reduction in tumor size was observed in 9.1% of the aged and 27.3% of the young, while one-year survival rate was 63.6% in the aged and 72.7% in the young. The common side effects were nausea and vomiting, while diarrhea was seen in 18.2% of the aged. Neutropenia, anemia and thrombocytopenia were found in both groups and the time course of myelosuppression in the aged (18.2 +/- 0.8 days) was significantly shorter than that in the younger patients (22.0 +/- 1.4 days, p less than 0.05). With regard to nephrotoxicity, creatinine clearance rate in the aged decreased remarkably from 56.9 to 38.9 ml/min, while there was no significant change in BUN, serum creatinine and urine NAG between the aged and the young. Disorders of electrolytes such as hypokalemia and hyponatremia were seen in 45.5% of the aged. We conclude that advanced lung cancer in the aged was effectively treated with cisplatin combination therapy with tolerable nephrotoxicity and myelosuppression.
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PMID:[Cisplatin combination chemotherapy in advanced lung cancer in the aged]. 260 73


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