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)

The tissue levels of two proteolytic enzymes, plasminogen activator and cathepsin B - like cysteine proteinase, which were found to be increased in malignant tumors and to be proportional to tumor metastatic potential in some instances, have been determined in a panel of solid metastasizing tumors in mice. The examination of B16 melanoma, MCa mammary carcinoma and of two lines of Lewis lung carcinoma with widely different potential to spontaneously metastasize, showed no correlation between metastatic potential and the tissue content of the proteinases considered. The treatment of the animals with cytotoxic antitumor drugs (CCNU, GANU, cisplatin, and cyclophosphamide) or with antimetastatic drugs acting with a mechanism unrelated with cytotoxicity (ICRF 159 and DM-COOK) caused only marginal inhibition in some instances, whereas no meaningful pattern of inhibition either based in terms of metastatic potential of the tumor or on drug mechanism of action was recognizable. A direct involvement of the two proteinases examined in the process of metastasis in the tumor panel used is thus not apparent, although a more complex interaction with other latent proteinases and inhibitors might be operative.
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PMID:Proteinases and proteinase inhibition by cytotoxic and antimetastatic drugs in transplantable solid metastasizing tumors in mice. 389 94

Between March 1979 und January 1983 122 patients with small-cell carcinoma of the lung were treated with different polychemotherapy regimen. 33 patients received VP-16-213 (etoposid), ifosfamide and vindesine (VPIV). 37 patients were treated with adriamycin, cisplatin and vincristine (APO). A third 3-drug combination, cyclophosphamide, methotrexate and CCNU (CMCC), was given to the remaining 52 patients alternating with the two other regimen. Response rates varied between 61% for the APO regimen and 85% for the VPIV regimen. The median survival was 10 months for patients treated with VPIV or APO and 12 months for patients treated with alternating drug combinations. This difference was not statistically significant. The rate of long-term survivors (longer than 2 years after diagnosis) was 9.9%. Side effects were seen more frequently in the group treated with APO.
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PMID:[3 multicenter phase II studies of the treatment of small cell bronchogenic carcinoma (incl. AIO studies BI + BII)]. 608 31

One hundred forty-seven eligible patients with small-cell carcinoma of the lung (SCCL) have been randomized to receive alternating (A) or sequential (S) combination chemotherapy. Initial treatment was with three cycles of VAM (A) or two cycles of POCC (S). VAM consists of VP16-213 200 mg/m2 intravenously (IV) day 1, Adriamycin (Adria Laboratories, Columbus, Ohio) 50 mg/m2 IV day 1, and methotrexate 30 mg/m2 IV day 1 repeated at 21-day intervals. POCC consists of cyclophosphamide 600 mg/m2 IV days 1 and 8, vincristine 1.5 mg/m2 (maximum, 2 mg) IV days 1 and 8, CCNU 60 mg/m2 po day 1, and procarbazine 100 mg/m2 po days 2 through 15. After initial treatment, all patients received whole brain radiation therapy (3,000 rad/10 fractions/2 wk). Patients with limited disease in addition received irradiation encompassing the tumor, hilar, mediastinal, and supraclavicular regions (5,000 rad/25 fractions/5 wk). After radiation, patients on arm A received POCC alternating with VAM; patients on arm S received POCC until progression when they were to be treated with VAM. The alternating arm was superior with respect to rate of complete remission (CR), median disease-free survival (MDFS), and median survival (MS). The advantage of alternating therapy was not as clearly demonstrated in the limited disease groups when interposition of involved field radiation delayed the initiation of the alternating schedule. In limited disease alone, comparing arm A with arm S, no statistically significant differences were noted. The CR rate was 42% v 54%, MDFS was 14 v 10 months, and MS was 16 v 10 months. In extensive disease, the CR rate was 44% v 20% (P = .03), MDFS was 6 v 4 months (P = .003), and MS was 10 v 7 months (P = .001). Improved treatment outcome in SCCL is achieved when combination chemotherapy regimens of similar effectiveness are administered in an alternating rather than sequential schedule.
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PMID:Chemotherapy of small-cell carcinoma of lung: a randomized comparison of alternating and sequential combination chemotherapy programs. 609 54

Eighty-three patients with histologically proven small cell carcinoma of the lung were entered into a prospective randomised clinical trial to evaluate two induction regimes. A 'low' dose methotrexate regime which employed three cycles of etoposide, adriamycin and methotrexate given at conventional dosage was compared with a regime which employed three cycles of etoposide and adriamycin together with five courses of high dose methotrexate and folinic acid rescue. All patients achieving a complete response (CR) received prophylactic cranial irradiation. Patients with limited disease who achieved a CR received additional radiotherapy to the primary site. An alternative four drug regime (procarbazine, vincristine, cyclophosphamide and CCNU) was evaluated in patients failing to achieve or subsequently relapsing from a complete response. Response rates for the low dose and high dose methotrexate arms were 54 and 55% respectively with median survivals of 8.6 and 9.7 months. Median survival for complete and partial responders was 20.2 and 11 months respectively. The alternative four drug regime showed limited activity in patients failing to achieve a complete response after primary therapy. We conclude that high dose methotrexate as used in this study has no role in small cell lung cancer. The 'low' dose regime was well tolerated by outpatients, is effective and is suitable for generalised use in the palliation of small cell lung cancer.
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PMID:Combination chemotherapy using high or low dose methotrexate for small cell carcinoma of the lung--a randomised trial. 610 Apr 97

Thirty-nine evaluable patients with squamous cell lung carcinoma were treated with combination chemotherapy consisting of doxorubicin, oncovin, bleomycin, cytembena and cis-platin. Objective responses were seen in 46 per cent of the patients. Patients with limited disease had a response rate of 56 per cent. Two of the four complete responses were endoscopically and histologically verified. The median survival time was 37.6 and 26.3 weeks for patients with limited and extensive disease, respectively (p less than 0.05), and 29.9 weeks for the whole group. Hematologic and gastrointestinal toxicities were moderate. There was one drug-related death due to septicemia and 2 reversible acute renal failures. The chemotherapeutic combination appears to be relatively effective. It causes some tumor regression and may extend the survival of responding patients with acceptable quality of life. Maintenance chemotherapy with CCNU, cyclophosphamide, methotrexate, procarbazine alternating with vinblastine, nitrogen-mustard, methotrexate, procarbazine, frequently had to be discontinued because of severe toxicity.
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PMID:Doxorubicin, vincristine, bleomycin, cytembena and cisplatin as combination chemotherapy for squamous cell lung cancer. 618 45

The antitumor effects of GANU have been examined in a panel of mouse tumors for which data appear to be lacking in the literature. GANU has significant activity against P388 leukemia and TLX5 lymphoma, and also against the solid tumors B16 melanoma and Lewis lung carcinoma; pulmonary metastases of this tumor are particularly sensitive to the effects of GANU. The effects of GANU on TLX5 lymphoma and Lewis lung carcinoma are less pronounced than those of BCNU and CCNU, as already reported for L1210 leukemia. In contrast with other results obtained with this tumor, chlorozotocin has a less pronounced effect than GANU, and virtually none in lung metastases of Lewis lung carcinoma.
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PMID:Antitumor effects of GANU and other nitrosourea derivatives against transplantable leukemias and solid tumors in mice. 622 44

Experimental studies with orally administered MCNU, a water-soluble nitrosourea, yielded the following results. MCNU produced a significant increase in life span, and 60-day survivors were observed by various schedules in L1210 leukemia. The therapeutic ratios of MCNU were almost similar to those of CCNU. With Lewis lung carcinoma and Ehrlich ascites carcinoma implanted into the stomach wall, its antitumor activity by oral administration was slightly more effective than by intravenous route. In Beagle dogs, hematologic toxicity and gastrointestinal toxicity (vomiting, diarrhea) were noted by oral administration, similar to intravenous administration, but its toxicity was mild. The maximum blood level of MCNU was noted at 30 minutes after oral administration in Beagle dogs. The half life (23.7 min) by oral administration was similar to that by intravenous route. From these results, the oral administration of MCNU deserves the consideration as a form of treatment now given other MCNU routes.
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PMID:[Experimental studies on oral administration of nitrosourea anti-tumor agent, MCNU]. 623 61

With the objectives of improving response rate, duration of response, and survival in small-cell carcinoma of the lung, 39 patients were randomized to remission-induction with either one of two potentially non-cross-resistant drug combinations: APE (consisting of adriamycin, 35 mg/m2 IV, D1 Q 3 weeks; procarbazine, 60 mg/m2 PO, D1-10 Q 3 weeks; and the epipodophyllotoxin (VP16-213), 130 mg/m2 IV, D8, 15 Q 3 weeks) or MOCC (composed of methotrexate, 15 mg/m2 IV (with [vincristine] Oncovin) or PO twice weekly D8-21 Q 3 weeks; Oncovin, 1.5 mg/m2 IV, D8, 15 Q 3 weeks; cyclophosphamide, 600 mg/m2 IV, D1 Q 3 weeks, and CCNU, 60 mg/m2 PO Q 6 weeks). A fixed crossover to the alternate regimen occurred at three months. Radiotherapy was delivered to the primary tumor (locoregional disease only) by a split course technique (1,750 rads for five days with a three-week split, followed by 3,400 rads over 17 days). The median survival including both arms was 11 months for regional and nine months for extensive disease. The chemotherapeutic activity of both regimens was comparable, with 15/17 (88 percent) of the patients responding to APE (including six complete) and 14/17 (82 percent) responding to MOCC (including five complete). The median survival for the complete responders was 11.7 months, while the partial responders survived for a median of 9.7 months. There were 2/9 (22 percent) responders to the alternate regimen at progressive disease. The overall incidence of CNS progression was 17 percent. The toxicity of the regimens was moderate, except for one instance of granulocytopenic death. This study establishes two equipotent drug combinations for the treatment of small-cell carcinoma of the lung.
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PMID:A controlled clinical trial testing two potentially non-cross-resistant chemotherapeutic regimens in small-cell carcinoma of the lung. 625 71

Two hundred and eighty-four patients with inoperable non-small cell lung carcinoma were randomized by the Eastern Cooperative Oncology Group to receive one of seven primary chemotherapy regimens: cyclophosphamide and methotrexate; Baker's antifol; vincristine, bleomycin, and methotrexate; melphalan; cyclophosphamide and CCNU (control arm); 5-FU procarbazine; and hexamethylmelamine, doxorubicin, and methotrexate (HAM). Patients with disease progression were eligible for treatment with VM-26 or ascorbic acid. HAM resulted in higher response rates than cyclophosphamide and CCNU in patients with adenocarcinoma (32%) and large cell carcinoma (23%). It was not tested in patients with squamous cell carcinoma. In terms of survival, HAM was significantly better than cyclophosphamide and CCNU in patients with limited disease. Its toxicity was predominantly hematologic and gastrointestinal. This regimen is being further evaluated by the Eastern Cooperative Oncology Group in patients with inoperable non-small cell lung carcinoma. Crossover therapy with VM-26 or ascorbic acid had no therapeutic benefit.
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PMID:Results of a phase II protocol for evaluation of new chemotherapeutic regimens in patients with inoperable non-small cell lung carcinoma (EST-2575, generation I). 626 76

The authors present the results of a non randomized study of 33 patients suffering from small cell carcinoma of the lung. After a similar course of monthly chemo-therapy (Endoxan Oncovin, Natulan, CCNU) and mediastinal irradiation in a dose of 30 grays in 10 fractions over two weeks, 14 patients were given adjuvant cerebral irradiation, the 19 others made up the control group (30 grays to the brain overall in 10 fractions over two weeks). With a minimum follow up for 12 months, 42% of the control group had evidence of cerebral secondaries, as opposed to none in the irradiated group with any neurological signs whatsoever. The indisputable efficacy of adjuvant cerebral irradiation contrasts with the absence of any significant improvement in survival time : 2 patients are alive and in complete remission, 1 in each group, while the mean survival was 12.3 and 11.7 months respectively. This is explained by the continued occurrence of extra-cerebral metastatic deposits such as the liver or mediastinum where the efficacy of systemic therapy remains uncertain. The therapeutic approach is currently orientated in two directions : - to raise the dose delivered to the mediastinum even if it appears radiologically normal. - to continue research into new chemo-therapeutic combinations more specifically active at the hepatic level.
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PMID:[Cerebral irradiation as adjuvant therapy in the treatment of small cell carcinoma of the lung (author's transl)]. 627 68


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