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)

A chemotherapeutic regimen consisting of BCNU, cyclophosphamide, vincristine, and procarbazine was evaluated in 43 patients with small cell carcinoma of the lung. The majority of patients received radiation therapy of the primary tumor, but chemotherapy alone was utilized in a group of patients with widely disseminated disease. In addition to thorough staging with radioisotope scans and bone marrow biopsies, a study of calcitonin and histaminase as biochemical markers was performed. The BCVP chemotherapy resulted in a complete and partial response rate of 53% when given alone or in conjunction with radiotherapy. The survival data are preliminary, but the complete responders do have a statistically significant better survival (mean of + -95 days) than the partial responders and nonresponders. Hypercalcitonemia was not detected in our patients, but elevated histaminase activity was found in eight of 24 patients with small cell carcinoma and in only one of 19 patients with squamous and large cell carcinoma.
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PMID:Management of small cell carcinoma of the lung: therapy, staging, and biochemical markers. 18 55

Fifteen patients with extensive small cell carcinoma of the lung and no prior therapy were treated with a chemotherapeutic regimen similar in intensity to the approach used in acute myelocytic leukemia. The patients received intensive induction therapy with cyclophosphamide, adriamycin, and VP-16-213 followed by treatment with a combination of BCNU, vincristine, methotrexate, and procarbazine. The objective response rate was 87% (13 of 15 patients) with three complete responses and ten partial responses. With the exception of one patient, the maximal response to therapy was achieved during therapy with the intensive cyclophosphamide, adriamycin, and VP-16-213 regimen. The three complete responders remain in remission for 159, 351, and 285 days but seven of the ten partial responders have relapsed and five of these have died. There was no unexpected morbidity associated with the intensive chemotherapy despite marked bone marrow suppression. This study demonstrates that very intensive combination chemotherapy can be safely used to achieve a high objective response rate in patients with extensive small cell carcinoma, but the complete response rate is low. An analysis of treatment failures and future directions is presented.
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PMID:Intensive induction therapy for small cell carcinoma of the lung. 22 Nov 17

Twenty-three patients with small cell carcinoma of the lung (15 with limited disease and eight with extensive disease) were randomized into one of two induction schedules of high-dose cyclophosphamide (CY), 60 mg/kg iv, given either on Days 1 and 2 or on Days 1 and 8. Following the high-dose CY, patients were treated with a sequence of three monthly courses of COMB (CY, 800 mg/m2; vincristine [Oncovin], 1.4 mg/m2; methotrexate, 20 mg/m2; and BCNU, 60 mg/m2) alternating with high-dose CY. The overall response rate to the high-dose CY was 70% with 17% being complete responses (CRs). COMB produced no additional responses. There was no significant difference in response rate with either high-dose CY schedule. There was no unexpected morbidity associated with the intensive regiment despite marked myelosuppression. The high-dose CY administered on Days 1 and 8 appeared less toxic than that given on Days 1 and 2. Laboratory studies demonstrated that small cell carcinoma cells respond to drug-induced humoral stimulation in vitro; and that tumor proliferation in vivo temporally coincides with increased serum stimulatory activity. This study demonstrates that high-dose CY is a safe and effective induction therapy for small cell carcinoma of the lung although the low CR rate obtained is disappointing.
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PMID:Intermittent high-dose cyclophosphamide chemotherapy for small cell carcinoma of the lung. 34 9

The nitrosoureas (BCNU, CCNU, methyl CCNU) represent a new class of antineoplastic agents with a broad spectrum of antitumor activity. They are cell-cycle nonspecific cytotoxic agents. Postulated modes of action and pharmacology of these nitrosoureas are reviewed. Their therapeutic effectiveness as single agents and in combinations have been recognized in malignant lymphomas, multiple myeloma, melanoma, glioblastoma multiforme, gastric and colorectal carcionma, and small-cell carcinoma of the lung. The nitrosoureas are administered on an intermittent 6--8-week schedule because of delayed and frequently severe bone marrow toxicity which may be cumulative in nature.
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PMID:Nitrosoureas: a reappraisal of clinical trials. 39 66

Nine patients with intracerebral metastasis from lung carcinoma were treated with intracarotid and intravertebral artery infusion of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Four of these patients considered definite responders showed unequivocal clinical improvement and definite decreases in the size of tumors evaluated by neurologic examination, computerized tomographic (CT) scan and radionuclide brain scan (RBS). One patient's clinical condition stabilized with doubtful improvement of diagnostic tests (probable responder). The remaining four patients had further unfavorable progression of the clinical and scan findings and were clearly nonresponders. Complications were transient and included: local pain in the eye, orbit, and occipital-nuchal area during infusion in 7 patients, focal seizure in 3 patients, mild confusion with disorientation in 2 patients, and nausea in 2 patients. Our findings suggest that intra-arterial BCNU therapy may be effective and may be used as an adjuvant to surgery and/or radiotherapy for the treatment of metastatic brain tumor from lung carcinoma.
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PMID:Intra-arterial BCNU therapy in the treatment of metastatic brain tumor from lung carcinoma: a preliminary report. 50 86

The therapeutic usefulness of chlorpromazine (CPZ) and caffeine (CAF) in combination with selected nitrosoureas was investigated in mice bearing L1210 leukemia, Lewis lung carcinoma, and B16 melanoma. We found that using BCNU with either CAF or CPZ was therapeutically superior to using either agent alone to treat mice bearing L1210 leukemia. Administering all three drugs in combination did not improve upon the therapeutic responses obtained with the two-drug combinations. In mice implanted with Lewis lung carcinoma or B16 melanoma, responses to treatment with the triple combination of methyl-CCNU, CAF, and CPZ suggested, but did not clearly establish, superiority over each two-drug combination or methyl-CCNU alone.
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PMID:Therapeutic potentiation of nitrosoureas using chlorpromazine and caffeine in the treatment of murine tumors. 75 16

A comparison has been made of the effects of three nitrosoureas (BCNU, CCNU, and methyl-CCNU) on the cells of Lewis lung carcinoma and B16 melanoma in vivo using a new in vitro method for assaying colony-forming cells. In addition, the effect on early hemopoietic precursors has been studied using the in vivo spleen colony assay and the in vitro agar colony assay. The results show that the three nitrosoureas are selective against Lewis lung carcinoma and B16 melanoma relative to normal hemopoietic precursors. Furthermore, the effect of these nitrosoureas is unchanged when the rate of proliferation of the hemopoietic precursor cells is increased.
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PMID:Differential sensitivity of colony-forming cells of hemopoietic tissue, Lewis lung carcinoma, and B16 melanoma to three nitrosoureas. 120 97

Fourteen patients with small cell carcinoma of the lung in relapse or with disease refractory to chemotherapy were treated with carmustine (BCNU) at doses of 600 to 1000 mg/m2 intravenously followed by autologous bone marrow transplantation. All patients previously were treated with cyclophosphamide, doxorubicin, vincristine, and etoposide. Seven of the 14 patients responded to the high-dose BCNU (50% response with 95% confidence limits ranging from 23% to 77%). Three patients had a complete response, and four had a partial response. Regrowth of tumor occurred within 60 days of treatment in the responding patients. Death occurred in six patients before the recovery of the platelet count to 50,000 cells/microliters. Although the response rate was high, the toxicity was excessive. In the dosage range of 600 to 1000 mg/m2 in heavily pretreated patients, BCNU is not recommended, but additional investigation may be warranted in patients with central nervous system metastases who previously were treated with radiation therapy.
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PMID:High-dose carmustine and autologous bone marrow reinfusion in the treatment of refractory or relapsed small cell lung carcinoma. 164 84

Beneficial antitumor effects of low-dose chemotherapy (Adriamycin, BCNU, cisplatin, 5-fluorouracil, methotrexate, 6-thioguanine or vincristine) combined with an immunotherapy with a partially purified polysaccharide of Viva-Natural, an edible seaweed extract, have been demonstrated against intraperitoneally implanted Lewis lung carcinoma in syngeneic mice. Adriamycin, cisplatin, 5-fluorouracil and vincristine at low doses, that were not effective when given alone, manifested antitumor activity when combined with the polysaccharide fraction of Viva-Natural. Other three drugs (BCNU, methotrexate and 6-thioguanine) at the noneffective low doses exhibited no further antitumor activity when combined with Viva-Natural. Cytotoxic activation of peritoneal macrophages in mice has been induced by single administration of the polysaccharide fraction of Viva-Natural, but the combined regimen of low dose drugs plus viva-Natural was no more effective than Viva-Natural alone. Therefore, the mechanism of action of the beneficial combination is not clear yet.
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PMID:Antitumor potential of low-dose chemotherapy manifested in combination with immunotherapy of Viva-Natural, a dietary seaweed extract, on Lewis lung carcinoma. 232 29

Aliphatic triazenes, such as 1,3-dimethyltriazene, are potent biological alkylating agents because they form alkyldiazonium ions. They are also subject to very rapid proteolytic decomposition, even at physiological pH. The acylated analogues 1,3-dialkyl-3-acyltrizenes are much more stable in aqueous solution, but they also give rise to alkyldiazonium ions. Four acylated 1,3-dimethyltriazenes, where the acyl groups were diethylphosphoryl (DMP), carbethoxy (DMC), acetyl (DMA), and N-methylcarbamoyl (DMM), were studied kinetically. Rate-pH profiles indicated that the acyl group had a profound effect on the mechanism of decomposition. The cytotoxic potential of all four compounds was studied in vitro by using the MTT-tetrazolium assay. The compounds had fair-to-good activity against some cell lines, particularly those deficient in methylation repair. In vivo assays of DMC and DMM against several tumor xenografts in nude mice showed promising activity for some cancers, particularly in the case of DMM. In vitro assays were also carried out on three 1-(2-chloroethyl)-3-methyl-3-acyltriazenes. The acyl groups were carbethoxy (CMC), acetyl (CMA), and N-methylcarbamoyl (CMM). The activity of these compounds largely paralleled that of bis(2-chloroethyl)-N-nitrosourea (BCNU), except for those cell lines which exhibited the Rem phenotype; triazenes were more active in those lines than BCNU. The in vivo activity of CMC, CMA, and CMM was tested in the P388 leukemia assay. All three were active but CMC and CMA proved to be rather toxic. CMM was well tolerated and was examined in several tumor xenografts in nude mice. Significant activity was found against MX-1 mammary carcinoma, against LX-1 small cell lung carcinoma, and particularly against LOX amelanotic melanoma, where complete cures were effected. The antineoplastic activity of the acyltriazenes is well-correlated with their chemical behavior.
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PMID:1,3-Dialkyl-3-acyltriazenes, a novel class of antineoplastic alkylating agents. 239 96


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