Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007131 (non-small cell lung cancer)
 22,601 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Preclinical and preliminary clinical data suggested a potentiation of the cytotoxic activity of cisplatin (CDDP) by interferon-alpha (IFN-alpha) in non-small cell lung cancer (NSCLC). This open, non-randomised, phase II study was set up to determine the response rate, duration of response, survival, safety and tolerability following treatment with the combination of recombinant IFN-alpha 2a and CDDP in NSCLC. 100 previously untreated patients with unresectable, measurable or evaluable stage III/IV NSCLC were enrolled for treatment with a combination of IFN-alpha 2a (9 MIU three times weekly) and CDDP (100 mg/m2 every 28 days). Patients were stratified according to histology, i.e. squamous cell carcinoma versus non-squamous cell carcinoma. The planned maximum treatment duration was 6 months or until disease progression. Responding patients could be treated with IFN-alpha 2a as maintenance for an additional 6 months. To be evaluable, the patients must have received at least 2 weeks of treatment with IFN-alpha 2a and at least one dose of CDDP. There were 75% male and 25% female patients with a mean age of 59 years (range 34-74). An overall response rate of 33% (95% confidence interval (C.I.) = 23-44) was achieved among the 84 evaluable patients. There was one complete responder and 27 partial responders, while 32 patients had stable disease. The duration of partial response ranged from 3 to 12 months. The median survival was 6.4 (95% C.I. = 5.7-8) months. The response rate in patients with stage IIIa disease (45%) was significantly higher (P = 0.047) than in patients with stage IV disease (22%). The median survival in patients with stage IIIa disease (9.3 months) was significantly longer (P = 0.025) than patients with either stage IIIb (6.3 months) or stage IV disease (6.2 months). The major forms of toxicity were gastrointestinal and constitutional symptoms of mild to moderate severity. The main severe adverse events (WHO grade 3-4) were nausea and vomiting (32%), anorexia (16%) and fever (11%). The most frequent severe haematological toxicities (WHO grade 3-4) were neutropenia (27%), anaemia (18%) and thrombocytopenia (10%). 13 patients experienced WHO grade 3-4 renal toxicity. This study confirms the antitumor activity of the combination of IFN-alpha 2a and CDDP in NSCLC. Further study of this combination is warranted.
 ...
PMID:Combination of cisplatin and interferon-alpha 2a (Roferon-A) in patients with non-small cell lung cancer (NSCLC). An open phase II multicentre study. 769 76

A late phase II trial on RP 56976 (Docetaxel) was carried out against stage IIIB or IV non-resectable non-small cell lung cancer as a multicenter cooperative trial. Of 78 enrolled patients, seventy five patients were eligible and 71 were evaluable for the response. The overall response rate was 19.7% (14/71): 27.9% (12/48) of patients with adenocarcinoma and 10.0% (2/20) of patients with squamous cell carcinoma responded to docetaxel. The response rate was 15.0% (3/20) in patients with stage III B disease and 21.6% (11/51) in patients with stage IV disease. Leukopenia (neutropenia) occurred frequently, but most tended to recover in a short period of time. Other adverse reactions included nausea/vomiting, anorexia, general malaise, alopecia, all of which were not severe. Severe hypersensitivity reactions occurred in 2 patients (2.7%). The results seemed to show usefulness of docetaxel for the treatment of patients with non-small cell lung cancer.
 ...
PMID:[Late phase II trial of RP56976 (Docetaxel) in patients with non-small-cell lung cancer]. 782 79

Oral BOF-A2 (Emitefur), a new derivative of 5-fluorouracil (5-FU) containing both 1-ethoxymethyl-5-FU (EMFU), a masked form of 5-FU, and 3-cyano-2,6-dihydroxypyridine (CNDP), an inhibitor of 5-FU degradation, was administered to 71 non-small cell lung cancer (NSCLC) patients in a multi-center phase II study. The patients were scheduled to receive at least 2 courses of treatment, each consisting of 200 mg twice daily for 2 weeks followed by a 2-week rest period. Out of 62 evaluable patients, 11 (18%) responded (8 of 44 adeno- and 3 of 15 squamous cell carcinomas). Thirty-four patients showed no change and 17 progressive disease. The incidences of grade > or = 2 hematologic toxicity were 5-8% for leukopenia, thrombocytopenia, and anemia. The incidences of non-hematologic toxicity of grade > or = 2, such as anorexia, nausea/vomiting, and diarrhea, were close to 20% or lower.
 ...
PMID:Efficacy of a new 5-fluorouracil derivative, BOF-A2, in advanced non-small cell lung cancer. A multi-center phase II study. 791 66

An early phase II clinical study of RP56976 (Docetaxel), a new anticancer agent of plant origin, was conducted in patients with primary pulmonary cancer as a multicentered study involving 28 Japanese institutions. Docetaxel was administered at an intravenous dose of 60 mg/m2 based on the results of a phase I clinical study, and efficacy and safety were examined. Of the 65 patients enrolled, 57 patients were evaluated to have completed the scheduled course of treatment by the Evaluation Committee. The antitumor effect in patients with non-small cell lung cancer was 21.4% (9/42). In patients not previously treated, the antitumor effect was 30.0% (6/20), in patients previously treated the antitumor effect was 13.6% (3/22), and in 13.3% (2/15) of patients with small cell lung cancer. This shows that docetaxel had an efficacy for non-small cell lung cancer. Hematological adverse reactions included leukopenia and neutropenia of Grade III or more as specified in the Adverse Event Reporting Form proposed by the Japan Society for Cancer Therapy in 53.3% (32/60) and 78.3% (47/60) patients, respectively. Other major adverse reactions included alopecia and anorexia. Neurological symptoms developed at a low frequency and were mild in severity.
 ...
PMID:[Early phase II clinical study of RP56976 (docetaxel) in patients with primary pulmonary cancer. Docetaxel Cooperative Study Group for Lung Cancer]. 797 21

A phase-I clinical study with coadministration of a new vinca alkaloid derivative KW-2307 with cisplatin (CDDP) at 80 mg/m2 to patients with non-small cell lung cancer was conducted by a collaborative study among 6 institutions. CDDP was given on day 1 and KW-2307 on days 1, 8 and 15, both intravenously. One 28-day course was specified to be repeated twice. The initial dose of KW-2307 was 15 mg/m2 and increased to 20 mg/m2 and then to 25 mg/m2. The numbers of enrolled subjects for each dose were 5, 8 and 12 cases, respectively, in the total 25 cases. This regimen as well as KW-2307 monotherapy induced leukocytopenia (neutropenia) as the main adverse reaction. The coadministration with CDDP tended to increase the occurrence of anorexia and nausea/vomiting. Tumor response was obtained in 5 among 24 evaluable cases (CR1, PR 4). The response rate in the cases untreated with KW-2307 and given at 20 mg/m2 or higher doses was 29.4% (5/17, 95% confidence interval of the response rate: 10.3 to 54.7%). Considering drug compliance, etc., the maximum tolerated dose in this regimen was supposed to be 25 mg/m2, and the recommended dose in phase-II study to be 20 mg/m2.
 ...
PMID:[Phase-I clinical study of KW-2307 combined with cisplatin in non-small cell lung cancer patients]. 800 39

A late Phase II clinical study of KW-2307, a new vinca alkaloid derivative, in previously untreated patients with non-small cell lung cancer was jointly carried out in 26 medical institutions. Of 80 enrolled cases, 75 cases were eligible, and PR was attained in 23 cases (30.7%). The main adverse effect of this drug, leukopenia (neutropenia), was observed in 62.7% (83.3%) of Grade 3 and 4 cases, but they recovered rapidly. In addition to decreased hemoglobin in 67% (Grade 3 in 5.7%) of the cases, adverse effects included slight disorder of hepatic function, anorexia, nausea and vomiting, fever, general fatigue, phlebitis, paresthesia and interstitial pneumonia. Peripheral neuropathy such as paresthesia occurred rarely and was slight, if any.
 ...
PMID:[Late phase II clinical study of KW-2307 in previously untreated patients with non-small cell lung cancer. KW-2307 Study Group (Lung Cancer Group)]. 808 45

Phase I study on a new vinca alkaloid derivative, KW-2307(vinorelbine), was conducted by multiple institutions in 40 patients with a variety of malignant tumors. KW-2307 was given intravenously by single administration or by weekly repeated for 4 weeks (hereinafter as the repeated administration). The initial dose, 10 mg/m2(ln), was escalated to 35 mg/m2(3.5n) in single administration and to 30 mg/m2(3n) in the repeated administration. A total of 35 cases were eligible for evaluation, consisting of 18 cases in single administration group and 17 in the repeated group. Both of single and repeated administration caused leukopenia dose-dependently, and the dose limiting toxicity (DLT) was judged as leukopenia. The maximum tolerated dose (MTD) was 30 mg/m2 in single administration and 25 mg/m2 in the repeated administration provided that administration is made weekly for 4 consecutive weeks. As subjective and objective adverse effects, general fatigue, anorexia, constipation, phlebitis etc. were observed, but all of these symptoms were relatively mild and recoverable. Peripheral neuropathy were found in two cases and judged as Grade 1. In this phase I study, a tendency of the decrease in tumor size was seen in 3 cases; 2 of non-small cell lung cancer and 1 of breast cancer. The pharmacokinetics of KW-2307 in blood after single administration showed a triphasic disappearance pattern with half-life of about 20 to 60 hrs. The data of pharmacokinetics after repeated administration revealed no accumulation of this agent. The recommended dose for early phase II study was supposed to be 20 to 25 mg/m2/week.
 ...
PMID:[Phase I clinical study on new vinca alkaloid derivative, KW-2307 (vinorelbine). KW-2307 Study Group]. 831 88

Phase II study of a novel combination regimen composed of cisplatin, carboplatin and etoposide (CPVP) was conducted against unresectable non-small cell lung cancer. The treatment schedule consisted of cisplatin 50 mg/m2 on day 1, carboplatin 200 mg/m2 on day 1, and etoposide 100 mg/m2 on days 1, 3, 5 every 3 or 4 weeks. The response rate and toxicities were evaluated in 28 patients, who were diagnosed and treated in the Cancer Institute Hospital (GANN-KEN) from March 1991 to September 1992. Partial response (PR) was found in sixteen out of 28 patients (57.1%). In myelotoxicities, 5 out of 28 patients (17.9%) showed grade 4 thrombocytopenia, but, white blood cell count and hemoglobin level stayed at grade 3 or milder in most patients, revealing safety of this regimen. In gastrointestinal toxicities, the median number of days in the patients suffered from nausea and loss of appetite was about 3 and 7 days, respectively. Median weight loss of the patients through the entire treatment was 2.3 kg. These results suggest that CPVP regimen is no less effective, but more tolerable, in other words, more favorable in QOL than standard regimens, and that it warrants further study in phase III trials.
 ...
PMID:[Phase II study of a novel combination regimen composed of cisplatin, carboplatin and etoposide against unresectable non-small cell lung cancer]. 838 50

The concomitant generation of macrophage-mediated suppressive events, as documented by the increase in neopterin and soluble interleukin-2 (IL-2) receptor (SIL-2R), and the enhanced production of cortisol, would represent the most investigated phenomena responsible for the reduced anticancer efficacy of IL-2 immunotherapy in humans. Based on our preliminary experimental studies suggesting a modulatory role of IL-3 on immune and endocrine effects induced by IL-2, a study was performed to evaluate the influence of IL-3 on biological effects of IL-2 cancer immunotherapy. We have evaluated 12 immunotherapeutic courses with IL-3 plus IL-2, which were performed in 6 patients with metastatic non-small cell lung cancer. The results were compared to those seen in 22 courses with IL-2 alone, carried out in 12 patients with metastatic non-small cell lung cancer. IL-3 was given intravenously at a daily dose of 1 microgram/kg/b.w. at 6 p.m. for 14 consecutive days, starting 7 days before IL-2. IL-2 was given subcutaneously at a dose of 3 million IU twice/daily for 5 days/week for 3 weeks. The increase in serum levels of the specific macrophage marker neopterin, induced by IL-2, was completely blocked by IL-3. The IL-2-induced SIL-2R rise was significantly lower during IL-3 plus IL-2 than under IL-2 alone. The increase in cortisol levels in response to IL-2 was neutralised by IL-3. The increase in lymphocyte, T lymphocyte, natural killer (NK) cell, activated T lymphocyte and eosinophil mean number was significantly higher during IL-3 plus IL-2 than during IL-2 alone. Episodes of fever, asthenia, anorexia, vomiting, anaemia and thrombocytopenia were significantly more frequent in patients receiving IL-2 alone than in those treated with IL-3 and IL-2. This preliminary study would suggest that IL-3 may improve the tolerability of IL-2 immunotherapy and enhance the biological antitumour properties of IL-2 by neutralising cortisol increase and macrophage-mediated suppressive events, with a following potential amplification of Il-2 anticancer efficacy.
 ...
PMID:In vivo biological results of the association between interleukin-2 and interleukin-3 in the immunotherapy of cancer. 839 Aug 45

Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
 ...
PMID:Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. 856 73


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>