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)

Thirty-one patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of folinic acid, fluorouracil, vincristine, and mitomycin (F-FOMi). Eight partial responses (26%), eight stable disease (26%), and 15 progressive disease (48%) were obtained. Patients with performance status (PS) 0-1 had a significantly better response rate than those with PS 2-3. Overall actuarial survival was 10 months. Toxicity was mild and mainly gastrointestinal with mucositis and diarrhea. F-FOMi seems to be comparable to regimens more widely used in the treatment of NSCLC.
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PMID:Advanced non-small-cell lung cancer (NSCLC) treated with folinic acid (F), fluorouracil (FU), vincristine (O), and mitomycin-C (Mi), (F-FOMi). 133 68

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

This phase I study investigated flavone acetic acid (FAA) given as a 12-h intravenous infusion every 3 weeks in the absence of urinary alkalinisation. Cohorts of three patients were treated at doses of 7, 10 and 13 g/m2. One subject had colon cancer; 5, renal cancer; and 3, lung cancer. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in four patients, 1 in two subjects and 2 in three cases. The maximum tolerated dose was 13 g/m2. The dose-limiting toxicities were WHO grade 3 hypotension and grade 3 diarrhoea. Other toxicities included lethargy and dizziness, nausea, temperature fluctuation, myalgia and dry mouth, but no significant myelosuppression was encountered. One patient receiving 10 g/m2 for renal cancer showed a partial response that lasted for 3 months and included the resolution of pulmonary and cutaneous metastases. The pharmacokinetics showed large interpatient variability. At 12-16 h post-infusion, the plasma elimination profile entered a plateau phase, with frequent increases in concentration suggesting enterohepatic recycling. Neither peak FAA levels nor AUC values were dose-dependent at the doses studied. Peak plasma levels were 101-402 micrograms/ml and AUC (0-48 h) values were 75-470 mg ml-1 min. Plasma protein binding varied with total concentration. Two metabolites were detected in the plasma, and both also underwent apparent enterohepatic recycling. Repeat dosing resulted in decreases of up to 48% in peak levels and AUC values for FAA in three of six patients. Of the total FAA dose, 39%-77% was excreted in the urine as FAA or metabolites within 2 days. The dose recommended for further phase II studies is 10 g/m2.
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PMID:A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. 155 Nov 73

The long-acting somatostatin analogue octreotide is a synthetic cyclic peptide consisting of 8 amino acids. Depending on the organ, it acts either as a hormone or as a neurotransmitter. The effect on various physiological functions in the brain and the gastrointestinal tract is mainly inhibitory. Due to its inhibitory actions, the possibility of intravenous and subcutaneous administration and the lack of serious side-effects, octreotide offers a broad spectrum of possible indications. Today octreotide is recommended in acromegaly patients and for the treatment of hormone dependent symptoms in patients with gastroenteropancreatic tumours. New indications are enterocutaneous and pancreatic fistulas and the prevention of complications in major pancreatic surgery. In patients with dumping and short-bowel syndrome, octreotide may be helpful until dietary regimens are established. In Aids patients with severe diarrhea, octreotide can be used to stabilize patients with severe dehydration and malnutrition. The clinical effectiveness on upper GI-bleeding due to gastric ulcer and oesophageal varices is still controversial. Future studies must prove whether octreotide may be helpful in treating diabetic retino- and nephropathy because of the possibility of suppressing growth hormone and IGF-I. The antiproliferative effect of octreotide also allows its use in patients with somatostatin-receptor-positive, non-endocrine solid tumors (e.g. brain, breast and small-cell lung cancer). A promising area is the scintigraphic visualization of somatostatin-receptor-positive tumors with a radio-labelled octreotide analogue and the possible target irradiation of these tumors by beta-particle emitting isotopes attached to such analogues.
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PMID:[Somatostatin analog (octreotide) in clinical use: current and potential indications]. 162 Oct 78

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) is a novel camptothecin derivative that has been selected for clinical evaluation because of its broad spectrum of antitumor activity in animal models and its unique inhibitory effects on mammalian DNA topoisomerase I. Seventeen patients with advanced non-small-cell lung cancer were treated with CPT-11 at weekly dose levels ranging from 50 to 150 mg/m2. At least three weekly doses were given to all patients except four, and a total of 74 weekly doses were given to the 17 patients. The dose-limiting toxic effects were myelosuppression (predominantly leukopenia) and unpredictable diarrhea. Gastrointestinal toxic effects were severe and not well controlled by standard therapy in some patients. Interpatient variability of toxic effects was substantial (including two deaths) and did not correlate with the pharmacokinetic parameters of CPT-11 and 7-ethyl-10-hydroxycamptothecin, its major metabolite. Two previously untreated patients, who received doses of 100 and 125 mg/m2, had partial responses lasting 3.2 and 4.0 months, respectively. The maximum tolerated dose on this schedule was 100 mg/m2, which we also recommend as a starting dose for phase II studies. This schedule appears to allow a CPT-11 dose intensity which is double the dose intensity possible on a once-a-month schedule. However, careful supervision to assess gastrointestinal toxic effects and myelosuppression is indispensable because of wide individual differences in drug tolerance.
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PMID:Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small-cell lung cancer. 165 62

We conducted a phase I study of CI-898 (trimetrexate), a new diaminoquinazoline antifolate in 22 patients with solid cancer in a multicenter collaborative study. The dosage schedule was single-dose intravenous administration (single treatment), followed by one or two courses of 5-day intravenous administration (5-day treatment) at 3-week intervals. Starting at 2 mg/m2 (1 n), the dose was increased up to 15 mg/m2 (7.5 n) for single treatment and 12 mg/m2 (6 n) for 5-day treatment. Evaluable cases numbered 18 for single treatment and 17 for 5-day treatment. In single treatment, the highest dose of 15 mg/m2 caused no serious side effect and did not reach the maximum tolerated dose (MTD). In 5-day treatment, leukocytopenia and thrombocytopenia were found dose dependently, the dose-limiting factor was bone marrow depression, and MTD was 10 mg/m2/day. The leukocyte and platelet counts reached the nadir in 1-3 weeks after initiation of 5-day treatment. The recovery from the nadir required about one week. Subjective side effects included mucitis (mouth, anus), malaise and gastro-intestinal symptoms (nausea, anorexia, diarrhea). None of alopecia, cardiotoxicity and nephrotoxicity were found. In the present phase I study, a tendency of tumor reduction was found in one case each of breast cancer (adenoma) and lung cancer (squamous cell carcinoma). The plasma concentration of the unchanged compound after single treatment showed a biphasic elimination pattern (t1/2 alpha 0.8-1.4 hr, t1/2 beta 9.4-13.0hr). The urinary excretion of the unchanged compound was 14.7-23.5% of the administered dose. In 5-day treatment, no accumulation was found. From the results of the present study, the recommended dosage of CI-898 in the early phase II study was considered to be 8 mg/m2/day intravenously for 5 days (every 3-4 weeks).
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PMID:[Phase I study of CI-898. CI-898 Study Group]. 183 40

An early phase II study of CPT-11 was carried out in patients with primary lung cancer in 15 institutions throughout Japan. The efficacy and safety of CPT-11 were studied at 200 mg/m2 based on the results of the previous phase I study. Thirty-eight of 52 enrolled patients were eligible. CPT-11 proved to be effective for primary lung cancer. The response rates were 20.0% (7/35) for non-small cell lung carcinoma and 33.3% (1/3 for small cell lung carcinoma. Hematological toxicities included leukopenia (less than or equal to 3,000) in 44.7% of the patients. Other major toxicities were nausea/vomiting (greater than or equal to grade 2) in 50.0% and diarrhea (greater than or equal to grade 2) in 47.4%.
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PMID:[An early phase II study of CPT-11 in primary lung cancer]. 184 91

A Phase II study of CPT-11, a new camptothecin, was performed in patients with primary lung cancer. Patients with previously untreated non-small cell carcinomas (group A), or previously treated non-small cell carcinomas (group B), and with small cell carcinomas (group C), were enrolled in this study. CPT-11 was given at a dose of 100 mg/m2 i.v. infusion once a week for three weeks or more. Out of 153 patients enrolled, 128 (A: 67; B: 26; C: 35) were assessed to be evaluable for response by an extramural review committee. Response rates were 34.3% (23/67) for A, 0% (0/26) for B and 37.1% (13/35) for C. The response rate was 50% for previously untreated patients (4/8), and 33.3% for previously treated patients (9/27) including 2 complete responses in the group C. Major toxicities were leukopenia, nausea/vomiting, diarrhea, anorexia and alopecia. Leukopenia and diarrhea were considered to be dose limiting toxicities, but they were reversible. It was, however, suggested that some patients should be monitored carefully for severe reactions and delay in recovery. The results showed that CPT-11 was highly effective against non-small cell and small cell carcinomas of the lung.
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PMID:[A phase II study of CPT-11, a camptothecin derivative, in patients with primary lung cancer. CPT-11 Cooperative Study Group]. 185 8

The present report describes a 69-year-old man displaying the clinical features of the Cronkhite-Canada syndrome. After taking medicine for the common cold, he suffered hypogeusia and watery diarrhea, eruptions on the lower extremities and an 8 kg loss in body weight. All his finger and toenails began to fall out. He underwent an upper gastrointestinal examination, upon which multiple polyps of the stomach were detected. Three years later, he again developed diarrhea, bloody stools, body weight loss and eruptions on the lower extremities. An upper gastrointestinal series showed a diverticulum of the esophagus and multiple polyps in the stomach. A barium enema examination revealed polyps throughout the entire colon. Endoscopical biopsy specimens revealed juvenile type polyps and adenomas. The patient was treated with predonine therapy and, in a few days, his symptoms improved. Following the predonine therapy, an upper gastrointestinal endoscopy revealed superficial esophageal cancer and early gastric cancer. The patient received successful surgical treatment. Macroscopically, the esophageal cancer was of the superficial type, and its histologic type was that of moderately-differentiated squamous cell carcinoma. The gross finding on the stomach cancer was one of superficial depressed type, and its histologic type was that of well-differentiated tubular adenocarcinoma. One year later, lung cancer was detected. The gross appearance of the resected lung tumor was one of a grayish-white color and the neoplasm was histologically diagnosed as undifferentiated carcinoma, small and large cell type. The coexistence of carcinoma of the gastrointestinal tract with Cronkhite-Canada syndrome has been reported in 21 cases. We have found no report, however, of lung cancer associated with Cronkhite-Canada syndrome. The case described herein is, therefore, the first case of Cronkhite-Canada syndrome to be associated with esophageal, gastric and lung cancer.
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PMID:Triple carcinomas in Cronkhite-Canada syndrome. 194 50

A phase I clinical study of intravenous Tegafur was conducted in nineteen previously treated patients with primary lung cancer. The dose of Tegafur was elevated from 1.0 to 3.0 g/m2/day for five consecutive days to determine the maximum tolerated dose. The dose-limiting factors were gastrointestinal and neurological toxicity and fatigability observed with the dose level of 2.5 g/m2/day for 5 days. Hematologic, hepatic and renal toxicities were not observed. Gastrointestinal toxicity including nausea, vomiting, anorexia and diarrhea of over grade 2 were seen to result from the dose of 2.5 g/m2/day. Neurological toxicity consisted of headache, dizziness, anxiety and depression. At the dose level of 2.0 g/m2/day, one patient, who had epileptic seizures in the past, experienced a psychomotor seizure. Depression (Grade 2 CNS toxicity) was observed at the dose level of 3.0 g/m2/day. Dose limiting factors were neurological toxicities. The pharmacokinetics of tegafur and 5-FU (the active form of Tegafur) has been studied in all patients. Serum level of tegafur was measured by HPLC method, and serum level of 5-FU was analyzed by GC-MS method. At the dose level greater than 2.0 g/m2/day for 5 days, the mean serum 5-FU values appear over the therapeutic range (0.1 micrograms/ml). In conclusion, 2.5 g/m2/day for 5 days was considered to be MTD, and 2.0 g/m2/day for 5 days intravenous administration was recommended for the phase II trial of single agent chemotherapy.
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PMID:[High-dose Tegafur (FT) for primary lung cancer: a phase I trial]. 201 1


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