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)

One hundred eighty-nine patients received a four-drug combination consisting of cyclophosphamide, Oncovin (vincristine), methyl CCNU, and bleomycin (COMB), according to three different drug regimens, performed sequentially. Of the 189, 62 had a partial response (33%) including 11/33 with squamous lung cancer, 11/32 with squamous carcinoma of the head and neck, 13/15 with oat cell carcinoma of the lung, and 7/41 with malignant melanoma. The response rate for patients with squamous lung or head and neck cancer appeared to be higher at weekly bleomycin doses of 30 and 60 mg (15/33 = 45%), compared to a weekly bleomycin dose of 15 mg (7/32 = 25%). A median survival from treatment of 30 weeks was observed in oat cell carcinoma, which represents considerable prolongation over that expected from supportive care alone or single-agent chemotherapy. Toxicity included: 1) myelosuppression, resulting in hospitalization for antibiotics in 20% of patients; 2) probable bleomycin lung damage in 4% of patients; and 3) dose-limiting vincristine neuropathy in 11%. The combination of twice-weekly vincristine and bleomycin for more than 6 weeks produced a disturbing "debilitation syndrome," characterized by weakness, anorexia, weight loss, and apathy. The encouraging response rate suggests a future role for these drugs in combination, especially for vincristine and bleomycin, with other agents showing activity in squamous and oat cell carcinoma. Toxicity precludes recommendation of this combination, in the regimens tested, for broader Phase III studies.
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PMID:COMB (cyclophosphamide, oncovin, methyl-CCNU, and bleomycin): a four-drug combination in solid tumors. 5 Aug 70

As bleomycin has up to now proved effective when used alone, the main thrust of current clinical investigations predominantly concerns its use in combination with other drugs. This has occurred along three broad patterns: 1) combination with vinca alkaloids which has been mainly in testicular carcinoma; 2) as part of multidrug regimens where bleomycin added for its lack of myelosuppression. This has occurred in the malignant lymphomas, lung cancer, and head and neck cancer; 3) in combination with radiotherapy which has taken place mostly in head and neck cervix cancer. To date, the combination of velban and bleomycin has had a major impact in improving the ability to induce complete remissions in advanced testicular carcinoma. Other drugs such as cis-platinum diaminedichloride and actinomycin D have been added and no definitive combination has been established. In the lymphomas the addition of bleomycin to the MOPP or CVP regimen has given higher complete response rates, but long-term survival data are still awaited.
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PMID:A review of the bleomycin experience in the United States. 8 99

The 49 patients with squamous cell type of cervical, lung, esophagus and head and neck cancers were treated with a sequential combination of bleomycin (BLM) and mitomycin C (MMC) as follows; 5 mg of BLM daily for 5 or 7 days followed by a single injection of 10 mg of MMC on day 6 or day 8. After one week of rest period, this course was repeated two to five times depending on the response or adverse effects. For cervical cancer, 17 patients out of 18 (94%) responded with complete remission (CR) in 13 (72%) and partial remission (PR) in 4 (22%). For lung cancer, four patients out of five responded. In two of the responders, metastatic tumors disappeared completely, but primary tumors decrease to about 10% in volume. For esophagal cancer, one patient out of 3 had CR after combining the BLM and MMC treatment with radiotherapy. For head and neck cancer, these were some differences in the response rates between two hospitals. In one hospital, 12 patients out of 22 (53%) responded, with CR in 4 (18%), whereas in the other hospital, 10 patients out of 11 (94%) responded, including eight with CR (72%). Regarding the toxicity, the overall incidence was very low, although lung complications were frequent. These results are promising with hopeful prospects for the control of advanced squamous cancers with metastasis.
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PMID:A sequential combination of bleomycin and mitomycin C in the treatment of advanced squamous cancers. 8 1

Gemcitabine (dFdC) and DMDC are new antimetabolites with good antitumor activities against various tumors which include human leukemic cell lines and a number of rodent and human solid tumors and human tumor. They are structurally related to cytarabine (Ara-C) which is known as one of the most effective drugs against adult acute leukemia, but many solid tumors are insensitive not been found to the drug. Gemcitabine acts as an inhibitor of ribonucleoside diphosphate reductase and inhibits DNA synthesis. Biochemically Gemcitabine is rapidly phosphorylated to dFdCTP which has a comparatively longer half-life than that of Ara-C, showing a therapeutic activity against tumors. In the phase I trials, the reported maximum-tolerated doses were 790 mg/m2 to 1370 mg/m2 at the schedule of 30 minutes i.v. infusion once a week for three weeks but higher dose levels (2,500 mg/m2 to 4,800 mg/m2) were reported in the schedule of prolongation of the infusion time. Reported toxicities were myelosuppression, fatigability, fever, appetite loss and skin rash. Toxicities were seemed to be mild. In USA, Europe and South Africa, phase II trials of Gemcitabine at the schedule of 30 minutes infusion once a week for three weeks followed by one week rest were performed against solid tumors (breast cancer, ovarian cancer, renal cancer, colorectal cancer, pancreas cancer, head and neck cancer, and lung cancer) and showed good responses to those tumors. DMDC was developed in Japan, and a phase I trial is currently on-going.
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PMID:[New antitumor antimetabolites--gemcitabine and DMDC]. 133 22

Topoisomerase I represents a unique new target that can be exploited for development of new antineoplastic agents. There are now two new topoisomerase I inhibitors that are in early clinical trials that have generated a tremendous amount of interest. Topotecan (SKF 104864-A) is a topoisomerase I inhibitor that has been explored in phase I trials using a variety of dosages and schedules. The dose-limiting toxicity of the agent is neutropenia. Other toxicities include alopecia, very mild nausea and vomiting, anemia, and occasional fever. Responses have already been noted in patients with advanced, refractory ovarian cancer and non--small-cell lung cancer. The drug is currently undergoing intense phase II testing. Irinotecan (CPT-11) is also a topoisomerase I inhibitor, which has already undergone extensive phase I and early phase II clinical testing in both Japan and the United States. Dose-limiting toxicities of the agent have included neutropenia and diarrhea. Responses have been noted in patients with refractory colorectal cancer, non--small-cell lung cancer, lymphoma, ovarian cancer, head and neck cancer, pancreatic cancer, and breast cancer. There is no doubt both of these agents will be important additions to our chemotherapy armamentarium.
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PMID:Clinical trials with the topoisomerase I inhibitors. 133 79

Data from the Surveillance, Epidemiology, and End Results (SEER) Program were used to compare the histological distribution of second lung cancer following an initial cancer of the lung, head and neck, and breast to primary lung carcinoma occurring as a first cancer. Following initial head and neck cancer or initial squamous cell carcinoma of the lung, the proportion of second primary lung cancer which was of squamous cell histology rose dramatically, while the proportion of pulmonary adenocarcinomas rose following initial adenocarcinoma of the lung. The histological distribution of lung cancer following an initial breast cancer in women was similar to the distribution of de novo lung cancer in women. These results persisted as the time interval between diagnosis of the two primaries was increased from 12 to 48 months. We conclude that the histology of a second primary lung cancer following an initial cancer of the lung or head and neck tends to repeat the histology of the initial cancer (field effect), and this observation is not likely to be due to misdiagnosis of a recurrence of the initial cancer.
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PMID:Differences in histology between first and second primary lung cancer. 130 75

Advances in the understanding of the process of carcinogenesis may allow prevention, diagnosis, and treatment of cancer to be approached at the molecular level. Studies in our laboratory show that growth factors (transforming growth factor alpha), dominant oncogenes (HER-2/erb B2 and K-ras), and tumor suppressor genes (p53) are functionally important in the maintenance of the malignant phenotype of human non-small-cell lung cancer cells. Application of these findings to clinical problems include the identification of p53 mutations as markers for malignant change in Barrett's epithelium, the use of discordant p53 mutations to diagnose second primary malignant neoplasms in patients with head and neck cancer, and the potential for therapy by the reversal of genetic lesions.
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PMID:Molecular surgery for cancer. 144 90

The need for validated intermediate end point markers to facilitate lung cancer chemointervention research is compelling. Three major classes of lung markers are relevant for this application. Since lung cancer includes four distinct histologies, markers that map degrees of histologic differentiation are important. Many of the markers for squamous differentiation overlap with the candidates for application in the study of head and neck cancer. Production of tissue-specific cell products especially for surfactant or CEA is of interest, because the gene structure is known and many differentiation-related polymorphisms exist. This strategy would be useful for adenomatous type tissue. A second type of marker is the broad group of differentiation markers. The carbohydrate or blood group-like antigens comprise a representative example. Carbohydrate structures are expressed in a specific sequence during fetal processes, and this sequence appears to reverse with the development of a cancer. Retrodifferentiation of specific differentiation markers is the basis of a major effort to effect earlier lung cancer detection using sputum immunocytochemistry. The final class includes markers which affect either positive or negative aspects of growth. Candidates in this area include growth factors or their receptors, or genes that regulate growth. If the intermediate end point marker reflects tumor biology and that biology is in the causal path of tumor progression, serial observation of that parameter should indicate the success of the intervention. In all three of these examples, the clinical material to be analyzed could be sputum specimens, bronchial biopsies or resected lung tissue. Systematic analysis of these markers in context of intervention trials is required to validate their utility.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Candidate biomarkers for application as intermediate end points of lung carcinogenesis. 146 99

Cisplatin (CDDP), 5-fluorouracil (5-FU), and hydroxyurea (HU) have individually demonstrated activity against several solid tumors, act synergistically with each other in vitro, and may act as radiation sensitizers. Therefore, we designed a phase I study to determine the maximally tolerated dose of cisplatin as given in addition to our previously described combination of 5-FU, HU, and concomitant radiotherapy (XRT). Patients exhibiting advanced solid tumors requiring palliative XRT were eligible. The regimen consisted of 1 g HU given p.o.b.i.d. on days 1-5, 600 mg/m2 5-FU given i.v. daily by continuous infusion (c.i.) on days 1-5, escalating doses of cisplatin starting at 10 mg/m2 daily given by c.i. on days 1-5, and involved-field XRT carried out on days 1-5. The cycle was repeated every 14 days until the target XRT dose had been reached. In all, 19 patients were entered at the first dose level, and cumulative grade 3-4 myelosuppression was seen in 16 subjects. As no dose escalation was feasible, the chemotherapy was subsequently altered by using the above regimen for cycles 1, 3, 5, and 7 and substituting the less myelosuppressive regimen of 1 g HU given p.o.b.i.d. on days 1-5, 400 mg/m2 5-FU given i.v. daily by c.i., and 100 mg leucovorin given p.o.4 h on days 1-5 for cycles 2, 4, and 6. On this alternating program, 28 patients were treated with escalating doses of CDDP. The dose-limiting toxicity was again myelosuppression, which was prohibitive at a CDDP dose of 20 mg/m2 daily. In the final phase of the protocol, 30 subjects were treated with the above alternating-cycle regimen at a CDDP dose of 20 mg/m2 daily and a decreased HU dose of 500 mg p.o.b.i.d. in an attempt to circumvent the myelosuppression associated with this dose of CDDP. Although severe acute toxicity (cycles 1 and 2) was observed less frequently, cumulative toxicity (all cycles) remained pronounced. The other major toxicity encountered was mucositis, which was particularly pronounced in patients receiving radiation to the head and neck and following leucovorin-containing cycles. Plasma concentrations of free platinum did not correlate with the CDDP dose, possibly due to the narrow range of doses given. Pharmacodynamic modeling demonstrated that the CDDP dose and the HU dose were associated with leukopenia. Antitumor activity was demonstrated in a number of solid tumors particularly non-small-cell lung cancer and head and neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:5-Fluorouracil, leucovorin, hydroxyurea, and escalating doses of continuous-infusion cisplatin with concomitant radiotherapy: a clinical and pharmacologic study. 173 49

The authors investigated the effects of radiation therapy on the immune system by studying lymphocyte subsets and other parameters in 32 patients undergoing radiation therapy for solid cancer. With monoclonal antibody techniques, we studied both T- and B-lymphocytes; cell suspensions were analyzed by means of a Facs Spectrum III Ortho (Ortho-Diagnostic) unit. The first control was performed right after the beginning of radiotherapy, when the dose to the patients was 50 Gy or higher. The second control was performed at 40 Gy because all patients received this dose. 30% of the patients exhibited lymphopenia from the beginning of the study; at 40 Gy the number of T-lymphocytes was low and helper/suppressor ratio was altered. A variable response of B-cells was observed, although all patients exhibited restoration of normal values at 6 months. Four patients only suffered from side-effects: a patient with tongue cancer presented oral mycosis, and a woman--treated for breast cancer--presented vaginal mycosis. Two cases of cystitis were also observed, after 18 Gy, in patients with uterine carcinoma undergoing pelvic irradiation. Disease progression was observed in 2 patients with head and neck cancer, while 3 patients died from lung cancer progression. Another one, with head and neck cancer, died because of heart failure.
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PMID:[Influence of radiotherapy on lymphocyte subpopulations]. 202 47


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