Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with Stage III non-small cell lung carcinoma continue to pose a therapeutic problem with dismal cure rates. In an effort to improve on these results, 129 patients with biopsy-proven clinical Stage III non-small cell lung carcinoma from November 1982 through November 1987, were entered into two consecutive Phase II studies at Rush-Presbyterian-St. Luke's Medical Center. Treatment in the first study consisted of Cisplatin and 5-Fluorouracil infusion with concomitant split course radiation; in the second Etoposide was added. Radiation and chemotherapy were given simultaneously on days one through five of each cycle in a preoperative fashion for four cycles in patients considered eligible for surgery and in a definitive fashion for six cycles in patients considered ineligible for surgery. Radiation was given in 2 Gy fractions for a planned preoperative dose of 40 Gy and a definitive dose of 60 Gy. Surgical resection was attempted four to five weeks later in patients treated preoperatively. Thus, 83 patients were treated preoperatively and 46 definitively. Eighty-three patients (64%) had IIIA disease and IIIB disease was found in the remainder of the patients. Sixty-two patients (75%) in the eligible for surgery group had a thoracotomy after the combined treatment with a resectability rate of 97% and an operative mortality rate of 5%. There were 17 patients (27%) with no evidence of residual cancer in the resected specimen. Three-year survival for the eligible for surgery group at 40% was significantly better than 19% observed in the ineligible for surgery group (p = 0.003). Seventy-six percent of the patients with no residual cancer in the resected specimen are recurrence-free at three years compared to 34% of the patients with gross residual. A total of 81 patients have failed after their treatment; 49 (59%) in the eligible for surgery group and 32 (70%) in the ineligible for surgery group. Of all the patients who failed, local failure alone and as a component occurred in 21 (26%) and 36 (44%) patients, respectively. Failure in distant sites alone was noted in 56% of the overall failures. Severe toxicity was unusual. There were three treatment related deaths (2%). Radiation esophagitis and pneumonitis were only mild to moderate seen in less than 10% of the patients. Survival rates and patterns of failure according to the stage of the disease, histology, treatment group and pathologic response will be presented in detail.
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PMID:Combined modality therapy for stage III non-small cell lung carcinoma: results of treatment and patterns of failure. 132 96

Chemotherapy is not a common treatment for cerebral metastases. The authors report results of combination chemotherapy with cisplatin (CDDP) and fluorouracil (5-FU). Sixteen men (age range 31-73 years) with brain metastases were treated with CDDP 20 mg/m2/day in continuous infusion for 5 days (d 1-5) and 5-FU 1 g/m2/day in continuous infusion for 4 days (d 1-4), and the treatment schedule repeated every 3 weeks. A brain computerized tomography after 2, 4 and 6 cycles was performed to assess efficacy. It was considered that complete response was achieved if no lesion was found on the CT scan, and partial response if at least half of the total volume had decreased. After 2 cycles, the response rate was therefore 8/16 (50%). Treatment toxicity was very mild with only 1 case of severe but reversible myelotoxicity (grade III). It is concluded that chemotherapy combination with CDDP and 5-FU is a useful treatment for brain metastasis of lung carcinoma.
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PMID:[Chemotherapy with cisplatin and 5-fluorouracil in inoperable brain metastases of bronchopulmonary cancers]. 175 34

Forty seven patients with inoperable adenocarcinoma and large cell carcinoma of the lung were treated with a combination of cisplatin (25 mg/m2), ifosfamide (1.5 g/m2), 5-FU (1.0 g/m2 c.i.) on day 1 through 4. The overall response rate (PR) was 34.8% with 16 partial responses. The median duration of response was 81 days. The median duration to show 50% decrease was 27 days. The median survival time was 359 days for all evaluable patients and 555 days for responders versus 196 days for non-responders. The side effects were mild and tolerable. The response rate of CIF therapy was same as the one reported in recent years but the survival time for responders was long and side effects were mild, suggesting that CIF therapy is an effective chemotherapy.
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PMID:[Clinical study of combination chemotherapy with cisplatin, ifosfamide, 5-FU (CIF therapy) of inoperable adenocarcinoma and large cell carcinoma of the lung]. 184 83

5-Fluorouracil (5FU) is rapidly metabolised in the liver by dihydrouracil dehydrogenase. Bromovinyluracil is formed in the liver from (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) by pyrimidine nucleoside phosphorylase and is a potent inhibitor of dihydrouracil dehydrogenase. The co-administration of 5FU (intravenously) and BVDU (orally) was investigated in normal BDF1 mice and in those bearing liver metastases of Lewis lung carcinoma. 5FU alone rapidly disappeared from plasma and liver within 60 min of dosing. Administered with BVDU, 5FU persisted in plasma and liver for 60-180 min. The combination also significantly enhanced the life-span of tumour-bearing mice. 5FU plus BVDU may have therapeutic potential in the treatment of primary and secondary liver tumours.
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PMID:Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on life-span and 5-fluorouracil metabolism in mice with hepatic metastases. 214 85

To investigate the characteristics in antitumor effects of 2-trimethylsilylethylthioethylamine(KAS-010) and its conjugate with 5-FU (KAS-011), the antitumor and immunomodulating activities of these silicon compounds were examined with various systems. Both KAS-010 and KAS-011 administered orally was found to be effective to B 16 melanoma, Meth A sarcoma and MM 46 mammary carcinoma in vivo. On the other hand, KAS-011 administered orally exhibited a marked antitumor activity against L 1210 leukemia bearing mice. Furthermore, these silicon compounds inhibited significantly metastases to the lymph nodes and lung of Lewis lung carcinoma implanted id into the right ear of BDF1 mice. Especially, KAS-011 in combination with tumor amputation resulted in a remarkable prolongation of the survival time (% ILS: 93.8%) in this antimetastatic model. The cell killing effect was mainly dependent on the exposure time of these silicon compounds in cultured KB and human lung cancer (OAT) cells. Moreover, a significant increase of delayed type hypersensitivity reaction (DTHR) to sheep red blood cell (SRBC) induced by KAS-010 was seen in old aged mice. The DTHR in B 16 melanoma and Ehrlich carcinoma bearing mice treated with KAS-010 was significantly higher than those of non-treated tumor bearing mice, indicating an enhanced cellular immunity to KAS-010 possibly resulting in a remarked antitumor effect. We also found that tumor free mice treated these silicon compounds were acquired specific tumor immunity to Meth A sarcoma and MM 46 mammary carcinoma.
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PMID:[Characteristics in antitumor effects of organic silicon related compounds]. 254 47

The aim of this study was to test cisplatinum and 5-FU chemotherapy. Thirty-five patients with epidermoid or undifferentiated lung carcinoma were entered in a multicentric phase II trial, in an attempt to further define the activity and toxicity of this association. None of them had been previously treated by chemotherapy. The dosage schedule was cisplatinum 100 mg/m2 D1 and 5-FU 1 g/m2 D1 to D5 every 3 weeks for 3 courses before evaluation. There were CR: 2, PR: 10, for a total response rate of 35%. Median survival was 7 months. Tolerance was acceptable. We conclude that this association can be safely administered, but that the results are not superior to others previously reported. Further studies are required to define the activity of a cisplatinum, 5-FU and radiotherapy association.
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PMID:[Results of a phase II study of the combination of cis-platinum and 5-FU in epidermoid or undifferentiated large cell bronchial cancer]. 256 18

New reactions of methyl 2,2-difluoro glycosides are described that were utilized for synthesis of some novel nucleoside derivatives. Thus, treatment of methyl 2-deoxy-2,2-difluoro-3,4-O-isopropylidene-alpha (beta)-D-erythro-pyranoside (2) with anhydrous HCl resulted in selective displacement of one fluorine atom with chlorine to give a 2-deoxy-2-chloro-2-fluoro glycoside 3. Reaction of 3 with silylated uracil in the presence of SnCl4 provided a 2-deoxy-2-fluoro-2-uracil-substituted glycoside 4. 2-Fluoro-2-deoxy glycosides substituted with other pyrimidines at C-2 were prepared similarly by the reaction of acylated 2,2-difluoro or 2-fluoro-2-bromo derivatives (5 and 6, respectively) with silylated pyrimidines. The resulting 2'-fluorinated isonucleosides were evaluated for their antitumor and antiviral activities. Compounds 7a,b, 8a,b, and 10a,b demonstrated 50% tumor cell growth inhibition in vitro (IC50) at 10(-4)-10(-5) M. At similar concentrations no antiviral activity was observed in vitro. Therapeutic activity was obtained with 7a,b and 8a,b in DBA/2 mice with L1210 leukemia. Administration of 7a,b at 500 mg/kg, ip daily, for 5 consecutive days, resulted in a 55% increase in life span (% ILS) while administration of 8a,b in the same manner at 200 mg/kg caused a 29% ILS. Treatment with 7a,b to mice with drug-resistant L1210 sublines (5-FU and araC) resulted in 22 and 57% increases in life span, respectively. Lewis lung carcinoma and M5076 sarcoma in mice also responded to the administration of 7a,b with reductions in tumor growth for both tumors and significant increases in life span in mice with Lewis lung carcinoma. Although the mechanism of action of 7a,b is not known, it has been found to be a relatively fast-acting, cell-cycle nonspecific cytotoxic agent that decreases [3H]deoxyuridine incorporation, blocks L1210 cells at the G2 phase of the cell cycle, and is not reversed by exogenous thymidine. These 2'-fluorinated isonucleosides have demonstrated biological activity and may have potential as antitumor drugs.
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PMID:2'-Fluorinated isonucleosides. 1. Synthesis and biological activity of some methyl 2'-deoxy-2'-fluoro-2'-pyrimidinyl-D-arabinopyranosides. 270 26

More than 1/3 of all non-small cell lung carcinoma (NSCLC) patients present with locally advanced non-metastatic disease. Despite radiation therapy and surgery the survival of these patients remains poor. In an effort to improve upon these results 33 clinical Stage III M0 patients from April 1985 through September 1986 were entered into a Phase II study at Rush-Presbyterian-St. Luke's Medical Center. Treatment included 5-FU by continuous infusion, VP-16, cisplatin and concurrent split course radiation therapy followed by surgical resection when possible. The overall clinical response rate is 74%. Fifty-seven percent of the preoperative group of patients went to surgery with a 100% resectability rate. These patients had a 50% pathologic complete response with no tumor found in the resected specimen. All surgical margins were free of disease and there were no operative deaths. This concurrent combined modality therapy is feasible with the major toxicities being leukopenia, nausea, and vomiting. With an overall median follow-up of 15 months, 36% of the patients remain alive. Overall local control is 71%. Actuarial observed 2 yr. survival is 33% and the median survival is 15 months. Histologic complete response appears to be an early indicator of the efficacy of this treatment regime. With 83% of the resected pathologic complete responders alive without evidence of disease, this preoperative combined modality therapy offers an appealing approach.
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PMID:Preoperative combined modality therapy for stage III M0 non-small cell lung carcinoma. 283 40

The antitumor activity of 5'-deoxy-5-fluorouridine (5'-DFUR) against Lewis lung carcinoma was examined by implanting the tumor subcutaneously into young (8-11 weeks) and old (24-41 weeks) hybrid (C57BL/6 x DBA/2)F1 (BDF1) male mice. Oral administration of 5'-DFUR induced a small (7 of 100) but significant (p less than 0.05) number of 70-d survivors in young mice. However, the antitumor activity was further enhanced in the old mice, and 15 of 46 (32.6%) and 11 of 62 (17.7%) mice survived for 70-d by treatment with 2000 and 1000 mg 5'-DFUR/kg/d, respectively, given on days 1, 5, and 9. The reason for the higher cure rate in old mice was partly analyzed. Toxicity of 5'-DFUR in young and old mice did not differ significantly, regardless of the presence (except 2000 mg/kg) or absence of Lewis lung carcinoma. No survivors were observed after treatment with 5'-DFUR when the tumors were implanted into the aged (15-38 weeks) syngeneic hosts, C57BL/6 mice. On the other hand, the survival time of BDF1 mice implanted with a constant number of the tumor cells increased significantly with the increase in host age and reached a maximum at the age of 24 weeks. These findings suggest that an optimal activation of 5'-DFUR (to 5-FU) was carried out in the old BDF1 mice bearing Lewis lung carcinoma and/or that a host-mediated antitumor mechanism of BDF1 mice, which is reinforced with aging, might participate in the enhancement of the antitumor activity of 5'-DFUR against this tumor.
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PMID:Enhanced antitumor activity of 5'-deoxy-5-fluorouridine against Lewis lung carcinoma in aged hybrid (C57BL/6 x DBA/2) F1 mice. 295 66

The blood level of PH-FU following oral administration to rabbits and tumor-bearing mice was considerably lower than that of Tegafur, HCFU or 5'DFUR, and decreased more rapidly. The t1/2 beta was 0.48 h (rabbits) and 1.74-1.91 h (mice). The blood level of 5-FU derived from PH-FU was higher at an earlier time after administration than that derived from other 5-FU derivatives, but it disappeared more rapidly. The tissue level of PH-FU in S-180-and Lewis lung carcinoma-bearing mice was detected at a low level in various tissues of mice, except for a higher level in the digestive tract and a lower level in the brain and muscle. The tissue level of 5-FU in both types of mice was high in the digestive tract and kidney. The 5-FU level in the 2 kinds of tumor tissues was relatively high and persisted for several hours. After incubating PH-FU and tissue homogenates from humans and mice at 37 degrees C for 2 h, PH-FU was converted to 5-FU very strongly in the liver and kidney, and considerably strongly in the muscle, heart, tongue and testis. In conclusion, PH-FU seems to be characterized by a low blood and tissue level of unchanged drug, a high production of 5-FU and a short duration of the level.
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PMID:[Pharmacokinetics of 1-phthalidyl-5-fluorouracil (PH-FU)]. 371 64


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