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)

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

CPT-11 is a new derivative of Camptothecin. Phase I clinical study of single administration with CPT-11 was carried out by a cooperative study group. Starting from 50 mg/m2 (n), dose was escalated to 350 mg/m2 (7n). Dose limiting factor was found to be a decrease in WBC counts (especially in neutrophils), and MTD was presumed to be 250 mg/m2 or more. Nadir of WBC counts was observed after about a week, and it took 2-3 weeks for recovery. The decrease in platelet number and hemoglobin content was mild. Other side effects included G-I toxicities, alopecia, etc. However, no toxic effects on the heart, kidney, lung were observed. SN-38, main metabolite of CPT-11, was observed in blood, and excreted rapidly. Anticancer effects were suggested with dose of 165 mg/m2 or more against colon cancer, gastric sarcoma, melanoma and lung cancer. It is suggested that the optimal dose schedule for an early Phase II study is 200 mg/m2 every 3-4 weeks. However, not only leukopenia but also marked G-I toxicities being noted in some cases, care should be taken for those side effects.
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PMID:[Phase I clinical study of CPT-11. Research group of CPT-11]. 240 54

Phase I study with a new oral purine antagonist, SM-108, was conducted in a total of 73 cases in a 5-day consecutive schedule with the dosage ranging from 20-2,500 mg/m2 at II institutes. The incidences of subjective and objective side effects were 20.5% (15/73) and 31.5% (23/73), respectively, however the correlation between these effects and their dosages was unclear. MTD and DLF values were not determined. SM-108 levels in serum reached maximum in 2-4 hours after oral administration of SM-108, and exhibited a dose-response relationship up to the dosage of 2,000 mg/m2/day. Forty to 60% of the administered drug was excreted into urine in 24 hrs; thus, the main excretory pathway was considered to be renal. An early phase II study was undertaken in patients with lung cancer in 5 cancer centers and university hospitals. Each patient had received 400 mg/m2/day (in two divided doses) or 600 mg/m2/day (in three divided doses) for more than 2 weeks. Only one case (adenocarcinoma) showed a minor response out of 27 cases but not reached partial response according to our criteria. In the 400 mg/m2/day group and the 600 m/m2/day group the incidences of subjective side effects (mainly GI tract disturbance) were 33.3% (4/12) and 40.0% (6/15), while objective side effects (hematological changes) were 16.7% (2/12) and 26.7% (4/15) respectively. In conclusion, we could not determine the dose limiting factor and maximum tolerated dose from our phase I clinical study and early phase II study for lung cancer.
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PMID:[Phase I study and early phase II of SM-108 (4-carbamoylimidazolium-5-olate) in lung cancer. SM-108 Study Group]. 264 91

In patients with small-cell lung cancer (SCLC), relapse with resistant disease often causes death. N901-blocked ricin (N901-bR), a murine monoclonal antibody (MAb)-blocked ricin immunotoxin, is a potential therapeutic for SCLC. N901-bR targets CD56, present on SCLC and cells of neuro-ectodermal origin. N901-bR kills up to 5 logs of CD56-positive cells at a concentration of 0.25 nM, while CD56-negative cells require 1000-fold more drug to achieve similar cell kill. We treated 21 patients with relapsed or refractory SCLC with a single 7-day course of N901-bR as a continuous infusion. We determined the MTD and toxicity profile, demonstrated drug binding to tumor cells in biopsies of lung, liver and bone marrow, and determined the time to development of human anti-mouse and anti-ricin antibodies. One patient had a documented PR and 6 patients demonstrated stable disease. Toxicity included transient elevation of liver enzymes, mild thrombocytopenia, hypoalbuminemia, fever, malaise, and evidence of capillary leak syndrome. Toxicities were controllable and reversible. No apparent drug-related central- or peripheral-nervous-system toxicity was noted by serial neurologic examinations, EMGs, and nerve conduction studies. Trials of N901-bR are planned in SCLC patients achieving CR and PR following chemoradiotherapy, and in relapsed/refractory patients. Anti-B4-bR will be added as an immunosuppressant in order to permit delivery of multiple courses of N901-bR. Additional trials will investigate synergy with conventional chemotherapeutics and the use of N901-bR as a sensitizing agent for chemotherapy-resistant tumors.
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PMID:Use of the immunotoxin N901-blocked ricin in patients with small-cell lung cancer. 751 30

CDDP, commonly used in cancer chemotherapy, behaves as not only effector but also modulator of 5-FU when combined with 5-FU and the derivatives. Therefore, the antitumor activity of combination treatment of BOF-A2, a new 5-fluorouracil derivative, with CDDP was evaluated with two human lung cancers (H-74 and LC-376) xenografted in nude mice. BOF-A2 was orally administered at 30 mg/kg (MTD) or 15 mg/kg (1/2 MTD) 3 times a week totally twelve times, and CDDP was administrated interperitoneally at 5 mg/kg (MTD) or 2.5 mg/kg (1/2 MTD) once a week totally 4 times. The antitumor effect of combination of two drugs at the 1/2 MTD was effective to H-74 and markedly effective to LC-376, and the effect was more remarkable than each drug administered individually at the 1/2 MTD, and the combination effect was additive. The effect by the combination was not synergistic but showed a similar activity compared with single drug given individually at the MTD. Moreover, the side effect of combination of the 1/2 MTD was less than group given MTD of CDDP in terms of body weight loss. These data suggests a clinical usefulness of combination BOF-A2 with CDDP against lung cancer.
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PMID:[Antitumor activity of combination treatment of BOF-A2 with CDDP against human lung cancers xenografted in nude mice]. 838 36

A phase I trial was performed to investigate the tolerability and efficacy of the novel nucleoside analogue gemcitabine in combination with cisplatin in the treatment of advanced non-small cell lung cancer. Both cisplatin and gemcitabine were administered as 30 min infusions weekly x 3 with a week of rest. There was one dose escalation of cisplatin from 25 mg/m2 (dose level 1) to 30 mg/m2 (in subsequent dose levels 2-5), such that the mean dose intensity for the weekly x 3 q 4 week cycle was 22.5 mg/m2/week which is close to that achieved with 100 mg/m2 bolus monthly. Gemcitabine was initiated at 1000 mg/m2 (dose levels 1 and 2) then escalated by 250 mg/m2/week to 1750 mg/m2 (dose level 5). Of 32 chemotherapy-naive patients entered (22 males, 10 females; median age 61 years, range 29-74 years), 11 had localized tumours (2 stage IIIa, 9 IIIb) and 21 had stage IV tumours with haematogenous metastases and a poor prognosis. Twenty-one patients had adenocarcinoma, 4 squamous cell carcinoma, 6 large cell undifferentiated tumors, and one had mixed squamous and adenocarcinoma. Dose-limiting toxicity was not seen in more than one patient in cycle 1 at any dose level. Grade 4 granulocytopenia and thrombocytopenia occurred more frequently with repeated dosing, necessitating dose reductions except at the lowest dose level (cisplatin 25 mg/m2, gemcitabine 1000 mg/m2). Non-haematological toxicity was mild and rapidly reversible. Cisplatin administration led to a higher frequency of nausea and vomiting than that seen with gemcitabine alone, but this was easily controlled with antiemetics. In the 28 patients evaluable, to date responses have been seen at most dose levels, with an overall response rate 35.7%. This phase I trial is ongoing and further dose escalation is intended to determine the MTD of gemcitabine.
Lung Cancer 1996 Feb
PMID:Phase I trial of gemcitabine and cisplatin in advanced non-small cell lung cancer: a preliminary report. 869 17

JM216 [bis-acetato-ammine-dichloro-cyclohexylamine-platinum(IV)] is an oral platinum complex that is currently in phase II trials in ovarian cancer and lung cancer on a daily-times-5 schedule. This trial examined an alternative schedule of two doses given 12 h apart, which may be better tolerated by patients. A total of 19 patients were given 50 cycles of treatment at doses ranging from 150 to 350 mg/m2 b.i.d. The study was stopped before the MTD was reached due to non-linear pharmacokinetics. Toxicity was similar to that encountered in previous phase I studies, with nausea, vomiting and diarrhoea being seen at all dose levels, although this was generally mild and short-lived, and grade 3 and 4 myelosuppression being seen at dose levels ranging from 250 to 350 mg/m2. There was no nephro-, oto-, or neurotoxicity, but one patient had an allergic reaction at 300 mg/m2 on the fifth and sixth cycles. No response was seen, but two patients with mesothelioma had stable disease and received six cycles. There was considerable interpatient variability in plasma pharmacokinetics at all dose levels. There was no relationship between dose and AUC (dose 1 and dose 2) or Cmax after dose 1. In a limited number of patients the first dose was given in the morning rather than in the evening, apparently resulting in lower AUC, Cmax and Tmax values at the 250-mg/m2 dose level, but this was not seen in one patient at 300 mg/m2. This study confirms that the pharmacokinetics of JM216 is non-linear and highly variable due to saturable absorption and that the daily times 5 schedule is the optimal schedule for further phase II trials.
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PMID:Phase I study of oral JM216 given twice daily. 965 14

A dose escalation study of paclitaxel in combination with vinorelbine was conducted in 21 patients with previously untreated stage IIIb or IV non-small cell lung cancer (NSCLC). All three patients treated with the initial dose of paclitaxel 135 mg/m(2) administered as a 1-h intravenous infusion and vinorelbine 25 mg/m(2) experienced dose-limiting toxicity (febrile neutropenia). After modification of the dosing schedule, the MTD of paclitaxel was found to be 115 mg/m(2) when combined with vinorelbine 20 mg/m(2) on day 1, followed by vinorelbine 20 mg/m(2) on day 5. Partial responses were achieved in 24% of patients, with a median duration of response of 126 days (range from 84 to 484 days) and a 1-year survival rate of 42%. In conclusion, haematologic toxicity (febrile neutropenia/neutropenia) severely restricts the dosing schedule of combined paclitaxel and vinorelbine, and possibly limits anti-tumour efficacy.
Lung Cancer
PMID:Phase I study of paclitaxel (Taxol) plus vinorelbine (Navelbine) in patients with untreated stage IIIb and IV non-small cell lung cancer. 1116 10

Gemcitabine is a new deoxycytidine derivative that shows a distinguishing, potent antitumor activity against various human tumor lines transplanted to nude mice. We have investigated the antitumor activity of gemcitabine combined with cisplatin (CDDP) or vindesine (VDS) using a lung cancer line, H-74, that was insensitive to almost all antitumor drugs and relatively insensitive to gemcitabine. We found that the antitumor effects of gemcitabine combined with CDDP or VDS were more potent and lasted longer than that of each drug alone, without an increase in side effects such as body weight loss. In this study, the antitumor activity of combined gemcitabine with topotecin (CPT-11) was evaluated using a similar method for 8 weeks, including a 4-week treatment period and a subsequent 4-week drug-free period, with reference to tumor growth inhibition rate, histological changes, and side effects. The treatment combining gemcitabine with CPT-11 administered at each 1/2 MTD showed an additive effect at 4 and 8 weeks after start of administration. Furthermore, no remarkable side effects were observed. Since these study results demonstrated that gemcitabine combined with CPT-11 increased and prolonged the antitumor activity without increasing side effects such as body weight loss, it is expected that CPT-11 could be one of the useful drugs used in combination with gemcitabine for lung cancer therapy.
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PMID:[Antitumor activity of combination treatment combining gemcitabine with topotecin against human lung cancer xenografted in nude mice]. 1197 42

A phase I study of gemcitabine (GEM) and docetaxel (TXT) combination chemotherapy was performed for unresectable non-small-cell lung cancer. Chemotherapy consisted of a fixed dose of GEM (1,000 mg/m2) on day 1, 8 and an escalated dose of TXT (50, 60, 70 mg/m2) on day 8 every 21 days, > or = 2 courses. Nine patients were entered (each dose level: 3 patients). Leukopenia, neutropenia, GOT increase, GPT increase, anorexia, fatigue, fever, and alopecia occurred, but no dose-limiting toxicity was found at any dose level and no MTD was reached. The recommended dose for the phase II study is GEM 1,000 mg/m2 and TXT 70 mg/m2 with consideration of application to outpatients and continuing courses.
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PMID:[Phase I study of gemcitabine (GEM) and docetaxel (TXT) combination chemotherapy for unresectable non-small-cell lung cancer]. 1246 92


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