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)

From June 1974 to October 1976, 288 patients with small cell undifferentiated lung carcinoma were entered into a randomized, controlled study comparing the two noncycle-active induction regimens of cyclophosphamide vs. the combination of cyclophosphamide, doxorubicin and imidazole carboximide (DTIC). Patients were stratified by extent of disease, previous radiotherapy and performance status. Responding patients and those who did not progress were then randomized to receive their initial regimen alone, or their initial regimen with added cycle-active therapy (vincristine, hydroxyurea and methotrexate). While only 4/34 (12%) evaluable patients treated with cyclophosphamide achieved a response (greater than 50% regression), a final total of 119/217 (57%) evaluable patients on the three drugs have responded (p = 0.005). The survival curve for all the combination-treated patients was significantly better than for those treated with cyclophosphamide alone (p = 0.012). There was no demonstrable statistical superiority in length of remission or survival for patients on the combination who received in addition cycle-active consolidation therapy. In the combination chemotherapy group, survival duration was longer for patients with limited disease than extensive disease (p = 0.035). There was a strong correlation between quality of remission produced by the combination and survival.
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PMID:The superiority of combination chemotherapy over single agent chemotherapy in small cell lung carcinoma. 22 97

Two dimethyltriazenoimidazoles, DTIC and BRL 51308, and a benzenoid dimethyltriazene, CB 10286, have been examined for their effects in mice bearing Lewis lung carcinoma. A slight reduction of primary tumor growth was found after treatment with DTIC and BRL 51308, whereas CB 10286 caused no significant effect. On the contrary, all the tested compounds sharply reduced the number of lung metastases and also resulted in a high proportion of animals free of metastases at death. No significant cytotoxic effect of the triazenes was observed in small established pulmonary tumors, as determined by evaluating the effects of treatment on the fractional incorporation of 3H-TdR into DNA of the lung colonies. These results are in contrast to those obtained with a purely cytotoxic agent, cyclophosphamide, and indicate that all three triazene derivatives tested have selective antimetastatic properties.
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PMID:Antimetastatic action of some triazene derivatives against the Lewis lung carcinoma in mice. 65 57

The combination of Interferon and low-dose cyclophosphamide synergistically inhibits the growth of human breast cancer xenografts, explanted human non-small cell lung carcinoma, and other experimental tumors. To determine whether this combination would demonstrate clinical efficacy against refractory solid tumors, we used recombinant alpha-2b-Interferon, 10 MU/m2 subcutaneously three times per week, and cyclophosphamide, 25 mg orally twice daily, in 42 patients (25 renal cell carcinoma, 17 melanoma). Two patients were inevaluable due to premature removal from the study. The toxicity profile did not differ substantially from that of Interferon alone with malaise, fatigue, fevers, and chills predominating. Sixteen percent of patients experienced an alteration in mental status. Of 40 patients evaluable for response, there were two partial responders (one renal cell carcinoma, one melanoma) and four minor responders (all renal cell carcinoma). The responder with melanoma had previously failed therapy with dacarbazine (DTIC). Seventeen patients remained stable for a median follow-up of 6 months. We conclude that this regimen is well tolerated; however, the combination of Interferon and low-dose cyclophosphamide used in this way does not appear to be superior to the same dose and schedule of Interferon used alone.
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PMID:Phase II trial of recombinant alpha-2b-interferon and low-dose cyclophosphamide in advanced melanoma and renal cell carcinoma. 327 75

Two lines of Lewis lung carcinoma with a different potential to metastasize spontaneously to the lungs have been examined for their cytological and histological characteristics. Metastatic potential appears to be related with parenchymal organization of the primary tumours, since large haemorrhagic areas containing detached tumour cells and the absence of endothelialized capillaries are observed only in the line with high metastatic potential. At the same time, the cytological characteristics of the cells of the two tumour lines are similar, and do not seem to be related with metastatic potential. After treatment with the selective antimetastatic drugs ICRF-159 and DM-COOK, and with DTIC, the histological appearance of the line with high metastatic potential becomes similar to that of the line with low metastatic potential. These data seem to indicate that the early phases of tumour spread occurring in the primary tumour are of relevance for metastatic potential and control by antimetastatic drugs, and suggest that for DTIC such antimetastatic action may participate to its clinical antitumour effects.
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PMID:Morphological analysis of metastatic potential and antimetastatic drug effects in mice bearing two lines of Lewis lung carcinoma. 365 53

The therapeutic efficacy of the preoperative administration of DTIC and its benzenoid analog DM-COOK, in terms of prolongation of the life-span of mice bearing Lewis lung carcinoma lines with different metastatic potential, has been evaluated in combined experiments with surgery and postsurgical non-specific immunotherapy with the peptidoglycan monomer PGM. The effects of the presurgical selective antimetastatic treatment with the dimethyltriazenes consist of a statistically significant prolongation of the survival time of the treated mice. The activity is more pronounced, in terms of animals cured, using the tumor line which is endowed of a low ability to colonize the lungs. The addition of postsurgical immunotherapy with PGM improves the overall therapeutic efficacy of the combined treatment with triazenes and surgery, independently from the tumor line used. In general, the presurgical treatment with the benzenoid triazene DM-COOK, causes antineoplastic effects slightly better than those observed using the imidazole derivative DTIC.
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PMID:Effects of dimethyltriazenes combined with surgery and non-specific immunotherapy in mice bearing Lewis lung carcinoma lines. 401 44

Seventy patients with small-cell lung carcinoma limited to the thorax +/- ipsilateral supraclavicular lymph nodes were randomized to either of two study arms: 33 patients received radiation therapy (RT) alone consisting of 4500 rads in 5-6 weeks to primary tumor and regional lymph nodes, and 3500 rads in 2 1/2 weeks to brain as prophylaxis; 37 patients received, in addition to the RT above, chemotherapy (CT) with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and DTIC (250 mg/m2) every 3 weeks given in two cycles before RT and seven cycles post-RT. Patients receiving RT alone who showed recurrence were crossed over to receive CT as above. Of 23 patients receiving RT alone who were evaluable 17 or 74% were responders; seven of these responses were complete (30%). On the RT and CT arm, of 24 evaluable cases, the response rate was 75%, of which 12 (50%) were complete. The median duration of disease-free survival of patients receiving RT + CT was 27 weeks, which ws superior to that of patients receiving RT alone (9.9 weeks, p = 0.019). The median survival of responders was essentially the same on both treatment arms; RT + CT, 47.7 weeks vs. RT alone, 50 weeks (p = N.S.).
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PMID:Combined modality treatment of localized small-cell lung carcinoma. A randomized prospective study of the Southeastern Cancer Study Group. 625 99

In a randomized trial of the Southeastern Cancer Study Group, patients with metastatic small-cell lung carcinoma were treated with a combination of cyclophosphamide (500 mg/m2 I.V.), Adriamycin (50 mg/m2 I.V.), DTIC (250 mg/m2 I.V.), and vincristine (1 mg/m2 I.V.) every 4 weeks for three cycles. Complete and partial responders to this induction regimen were then randomized to receive either the same combination every 4 weeks for an additional six cycles versus a non-cross-resistant drug combination of BCNU (100 mg/m2 I.V.), procarbazine (100 mg/m2 p.o. daily x 10 days), methotrexate (25 mg/m2 I.V.), and vinblastine (5 mg/m2 I.V.) every 4 weeks for six cycles versus alternating treatments with the two regimens for a total of six cycles of therapy. Patients who were less than good responders received six cycles of the non-cross-resistant drug combination. Of 202 evaluable patients, 40% responded (complete + partial responses) to induction; the complete response rate for the whole group was low (14%). Patients randomized to the BPMV combination, or crossed over to it, failed to improve upon their response to induction. Patients who responded to induction had a median survival of 41 weeks versus 20.6 weeks for the nonresponders, p less than 0.001. Performance status greater than or equal to 60%, and absence of prior radiotherapy were associated with improved survival (30 and 31.5 weeks, respectively). The toxicity of these regimens was acceptable. Failure to improve on results of our earlier protocol were probably due to the long (weeks) interval between treatments, inclusion of a relatively inactive but toxic drug (DTIC) in the induction combination which limited doses of the more active agents, and the use of a non-cross-resistant drug regimen which was inactive.
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PMID:Alternating non-cross-resistant drug combinations in the treatment of metastatic small-cell carcinoma of the lung. 626 9

Sixty-six patients were entered into a prospective, randomized clinical trial evaluating the use of alternating noncross-resistant chemotherapy in patients with extensive small cell carcinoma of the lung. Sixty-five were evaluable. One regimen utilized cyclophosphamide, VP-16, vincristine, cisplatin alternating with doxorubicin (Adriamycin) and DTIC (CVVP-AD). The second regimen utilized doxorubicin, VP-16, vincristine, and cisplatin alternating with cyclophosphamide and DTIC (AVVP-CD). There was no statistically significant difference between the two chemotherapeutic programs in terms of regression rate, time to progression, or survival. Overall regression rate for CVVP/AD was 91% (29/32) including five complete regressions (CRs). For AVVP-CD, the total regression rate was 82% (27/33) including nine CRs. Combined, the overall regression rate was 86% with a CR rate of 22%. Time to progression for CVVP-AD and AVVP-CD was 28 and 26 weeks, respectively. The median survival time of CVVP-AD and AVVP-CD regimens was 40 and 42 weeks, respectively. Prognostic variables significantly correlated with survival were performance score and extensive liver metastases at diagnosis. Correlations between initial sites of disease led to the observation that patients with no central nervous system (CNS) metastases at diagnosis were more likely to have more extensive liver and lung involvement. Further analysis revealed the lung to be the most common site of first progression (46%) and liver second (28%). Patients with extensive involvement of the liver or lung progressed sooner in these sites than those with a lesser tumor extent. At some point in the study, 40% of the patients experienced CNS metastases. The efficacy of these two alternating regimens is comparable to most current regimens reported in extensive SMCLC. Whether cyclophosphamide or doxorubicin is used first seemed to make little difference. The alternate noncross-resistant regimen was rarely effective in producing tumor regression following initial progression.
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PMID:Evaluation of alternating chemotherapy and sites and extent of disease in extensive small cell lung cancer. 627 81

The effects of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) and its benzenoid analog p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) have been examined in mice bearing two Lewis lung carcinoma lines with different potential to spontaneously metastasize to the lungs. DTIC similarly depresses the growth of intramuscular and pulmonary tumor nodules, and also reduces the development of spontaneous lung metastases for both tumor lines. DM-COOK causes effects similar to those of DTIC on the tumor line with low metastatic potential; on the contrary, although it is highly active in inhibiting lung metastasis formation for the line with high metastatic potential, it is ineffective or marginally cytotoxic on intramuscular or on pulmonary tumor nodules, respectively. These data indicate, at least for the dimethyltriazene DM-COOK, a dissociation between sensitivity to cytotoxic and antimetastatic effects, and that tumor cell populations with a higher potential to spontaneously metastasize have a greater sensitivity to selective antimetastatic effects, concomitant with a reduced cytotoxic response to the effects of this drug.
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PMID:Effects of antimetastatic dimethyltriazenes in mice bearing Lewis lung carcinoma lines with different metastatic potential. 648 Feb 89

The effects of a selective antimetastatic agent: the aryldimethyltriazene derivative 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) have been examined on two in vitro tumor cell lines derived from lung metastases of Lewis lung carcinoma. These stabilized in vitro tumor cell lines named C108 and BC215 have been reported to differ in their metastatic potential evaluated as lung colony forming ability and as the number of spontaneous metastases produced after intramuscular implant of tumor cells. The cytotoxic effect of DM-COOK in vitro was also compared with the one demonstrated by the structure-related compound 4-(3,3-dimethyl-1-triazeno)imidazole-5- carboxamide (DTIC) on the same variant lines. Survival curves show a different chemosensitivity of the two in vitro lines to the DM-COOK treatment, whereas no differences were detected between C108 and BC215 after exposure to DTIC. Moreover, DM-COOK and DTIC exhibit different trends of cell killing, implying different mechanisms of action for the two drugs. Results are discussed in view of the selective in vitro action of the aryldimethyltriazene derivative DM-COOK on cells which express a high metastatic potential.
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PMID:Effects of dimethyltriazenes on in vitro Lewis lung carcinoma tumor lines with different metastatic capacity. 648 Feb 90


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