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)

We conducted a randomized phase II trial of two different schedules of topotecan in patients with advanced-stage non small lung cancer (NSCLC) without prior cytotoxic chemotherapy. All patients had histologic or cytologic confirmation of stage IV (M1) or III-B NSCLC. Patients were stratified by performance status, stage and weight loss. Patients were randomized to receive topotecan at intravenous doses of 1.5 mg/m(2)/day over 30 min for 5 days every 3 weeks (Arm A) or 1.3 mg/m(2)grade 3 in both arms included leukopenia, thrombocytopenia, malaise, constipation, diarrhea, lethargy, pulmonary, vomiting, infection and myalgia. Severe (> or = grade 3) thrombocytopenia occurred in 15.8% of Arm A patients and 37.8% of Arm B patients and this difference was statistically significant (P=0.03). The median times to progression are 101 and 63 days (P=0. 75) and the median survival times are 257 and 179 days (P=0.83) for Arms A and B, respectively. These differences in time to progression and overall survival are not statistically significant. Topotecan has limited, single agent activity in advanced NSCLC when given as 1. 5 mg/m(2)/day over 30 min for 5 days every 3 weeks. We do not intend to pursue further investigations with topotecan in patients with NSCLC.
Lung Cancer 2000 May
PMID:A randomized phase II trial of two schedules of topotecan for the treatment of advanced stage non-small cell lung cancer. 1071 33

The purpose of the present trial was to determine the activity of gemcitabine as a second-line chemotherapy for non small cell lung cancer (NSCLC). To be eligible, patients had to have pathologically proven NSCLC that has failed to respond to a first-line chemotherapy with a cisplatin-containing regimen, a Karnofsky performance status greater than 50 and adequate renal, haematological and hepatic functions. After registration, patients were treated by gemcitabine given i.v. at a dose of 1 g/m(2) on days 1, 8, 15 every 4 weeks. Response was assessed after two courses of therapy. Eighty-two patients have been registered, five are ineligible and 65 are assessable for response. Four partial responses were observed (6%). No change was documented in 18 cases (28%). Tolerance was good. A few grade III leucopenia and grade III-IV thrombopenia were observed. We conclude that gemcitabine has a modest activity as second-line chemotherapy for NSCLC. It has the advantage to be well tolerated and may thus be one drug to be proposed to the patients who have disease progression after a first-line chemotherapy and who ask for further treatment.
Lung Cancer 2000 Jul
PMID:A phase II trial testing gemcitabine as second-line chemotherapy for non small cell lung cancer. The European Lung Cancer Working Party. 101473.1044@compuserve.com. 1088 Aug 49

We conducted a phase II study of tamoxifen, ifosfamide, epirubicin, and cisplatin (TIEP) chemotherapy in patients with non-small cell lung cancer (NSCLC) who had failed previous chemotherapy, in order to assess the response and toxicity of TIEP. Between November 1997 and May 1999, 25 patients were treated. Twelve of the 25 patients (48%) had been previously treated with cisplatin-based combination chemotherapy. TIEP doses were tamoxifen 60 mg oral twice daily on days 1-3; ifosfamide 2.4 g/m(2) intravenous infusion (IV) 60 min with mesna on day 2; epirubicin 40 mg/m(2) IV bolus on day 2; and cisplatin 50 mg/m(2) IV 60 min on day 2 every 4 weeks for up to six cycles. Seventy one cycles were given to 25 patients, with a median of three cycles (range one to six cycles). All patients were evaluable for toxicity profile and response rate. As expected, the major toxicity was myelosuppression. Grade 3 or 4 neutropenia occurred in 15 patients (60%) during treatment, as well as in 31% of the total courses. Febrile neutropenia occurred in two patients. No toxic death occurred in this study. Grade 3 thrombocytopenia occurred in five patients with five cycles. Toxicities other than myelosuppression were few and mild in severity. After two cycles of treatment, five of 25 patients (20%) had a partial response (95% confidence interval 4.3-35.7%). Among 12 patients previously treated with cisplatin-based chemotherapy, three patients (25%) achieved a partial response. The median time to disease progression was 4.9 months and median survival was 7.7 months. The response rate and median survival were better than in our previous study of salvage chemotherapy with ifosfamide, 5-FU, and leucovorin; and with ifosfamide, epirubicin, 5-FU, and leucovorin. In conclusion, TIEP appears to be an active combination regimen with an acceptable toxicity profile in Chinese patients with NSCLC who have failed previous chemotherapy.
Lung Cancer 2000 Aug
PMID:Phase II study of tamoxifen, ifosfamide, epirubicin and cisplatin combination chemotherapy in patients with non-small cell lung cancer failing previous chemotherapy. 1096 44

The anthracenedione analogue, BBR 2778 is an active antitumour agent preclinically and has reduced potential for cardiotoxicity compared with other similar drugs in preclinical models. BBR 2778 was administered 3 weekly by a 1 h intravenous (i.v.) infusion to 24 patients and the dose escalated rapidly from 20 to 240 mg/m2. The dose-limiting toxicity (DLT) was neutropenia, common toxicity criteria (CTC) grade 4 in 3/5 patients at 240 mg/m2. Other toxicities > or = CTC grade 3 were: vomiting, lymphopenia, thrombocytopenia and lethargy. Blue discoloration of veins and urine was also noted. In 1 patient (120 mg/m2, four cycles) left ventricular ejection reaction (LVEF) fell (CTC grade 2) but with no clinical sequelae. BBR 2778 plasma pharmacokinetics were biphasic (mean t(1/2) at 180 mg/m2 = 14.1 h) and the urinary elimination of the unchanged drug was < 10%. In a patient with previously treated small cell lung carcinoma (SCLC), a 49% reduction in measurable disease was noted with resolution of pericardial and pleural effusions (120 mg/m2 x eight cycles). From the results of this phase I study a dose of 180 mg/m2 as a 1 h infusion every 3 weeks would be recommended for phase II trials.
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PMID:A clinical phase I and pharmacokinetic study of BBR 2778, a novel anthracenedione analogue, administered intravenously, 3 weekly. 1109 9

The aim of the present study was to determine the clinical activity and toxicity of a novel chemotherapy combination regimen of gemcitabine, ifosfamide and cisplatin (GIP), administered every 3 weeks, in patients with inoperable non-small cell lung cancer (NSCLC). From October 1998 to July 1999, 18 previously untreated stages IIIb (4) and IV (14) patients were enrolled into the study. Gemcitabine and ifosfamide (with mesna as uroprotection) was administered on days 1 and 6, at a dose of 1000 and 1500 mg/m2, respectively; and cisplatin was given on day 1 at a dose of 60 mg/m2, every 3 weeks. All 18 patients were evaluable for response and toxicity profiles. One patient achieved a complete response, and II patients achieved a partial response, with an overall response rate of 66.7% (95%, CI, 45-89%). The main toxicity was hematological, a NCI grade 3-4 neutropenia in 16 patients (88.9%) during the treatment course. Febrile neutropenia occurred in three patients (16.6%). Grade 3 anemia occurred in eight patients (44.41%) and grade 3-4 thrombocytopenia occurred in 11 patients (61.1%). Non-hematological toxicity was mild and tolerable. No toxic death occurred. The median survival was 12.7 months and 1 year survival was 58.4%. The GIP combination chemotherapy produced a high response rate in advanced NSCLC; however, there was a relatively high percentage of hematological toxicity that still could be tolerated. A randomized trial comparing GIP to a two-drug combination of gemcitabine and cisplatin is planned.
Lung Cancer 2000 Dec
PMID:Phase II study with gemcitabine, ifosfamide and cisplatin in advanced non-small cell lung cancer. 1113 5

In a multicenter phase II Italian trial that used a 28-day dosing schedule of gemcitabine on days 1, 8, and 15 and cisplatin on day 2, thrombocytopenia and neutropenia were the main dose-limiting toxicities observed. The aim of the present study was to determine whether using 15-day cisplatin in lieu of the standard 2-day schedule in combination with weekly gemcitabine would decrease expected myelotoxicities, particularly thrombocytopenia. Fifty-one patients with advanced non-small cell lung cancer (NSCLC), a median age of 62 years (range 31-76) and baseline Eastern Cooperative Oncology Group (ECOG) performance status scores of 0-1, were enrolled. Twenty-four patients had stage IIIA-B disease and 27 had stage IV. Patients received gemcitabine 1000 mg/m(2) on days 1, 8, 15, and cisplatin 100 mg/m(2) on day-15, every 28 days for a total of 151 cycles. All patients were evaluable for toxicity. Grades 3 and 4 thrombocytopenia was observed in 16% of patients, grades 3 and 4 neutropenia in 35% of patients, and grade 3 anemia in 4% of patients (no grade 4 anemia). Nonhematologic toxicity was mild. Two patients had grade 3 vomiting, and another had grade 4 hepatic toxicity only after gemcitabine administration. The dose intensity of gemcitabine and cisplatin was well maintained. Of the 45 patients evaluable for response, there were 22 (49%) partial responders, 7 (15.5%) minimal responders, 9 (20%) with stable disease, and 7 (15.5%) progressions. Compared with the schedule used in a multicenter phase II Italian trial (day 2 cisplatin), day-15 cisplatin decreases incidences of thrombocytopenia (16 vs. 52%) and anemia (4 vs. 25%); the occurrence of neutropenia is similar (35 vs. 36%). Response rates are also similar (49 vs. 54%).
Lung Cancer
PMID:Decreased myelotoxicity of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC) with cisplatin infusion on day 15. 1116 7

Based on the results of our previous pilot study, we conducted a multi-institutional phase II study of combination chemotherapy consisting of oral UFT (Taiho Pharmaceutical Co. Ltd, Tokyo) plus cisplatin (CDDP) in patients with advanced non-small cell lung cancer (NSCLC). UFT capsule containing 100 mg tegafur and 224 mg uracil was orally administered in two divided doses on days 1 through 21 making the total tegafur dose 400 mg/m(2)/day (maximum 600 mg/body). CDDP was administered by drip infusion at a dose of 20 mg/m(2) on a 5-day schedule from day 8 to 12. Treatment was repeated every 4 weeks as long as the criteria for initiation of therapy were still met. Between April 1995 and March 1997, 51 patients were entered into the study. The mean age of all 50 eligible patients was 64 years(range: 40-78). There were 21 patients with clinical stage IIIB disease and 29 patients with IV disease. Thirty-two patients had adenocarcinoma, 14 had epidermoid carcinoma, and four had large cell carcinoma. Of the 47 assessable patients, 18 achieved a partial response with an overall response rate of 38.3% (95% confidence interval: 24.4-52.2%). The median response duration was 113 days. The median survival time of the eligible patients was 12.8 months, and the 1-year survival rate was 54%. Among the 51 patients enrolled, grade 3 or 4 leukopenia developed in one patient (2%), neutropenia in six patients (11. 8%), thrombocytopenia in six patients (11. 8%), and anemia in three patients (5. 9%). Non-hematological grade 3 or 4 toxicities included anorexia in 10 patients (19.6%), nausea in ten (19.6%), vomiting in two (3.9%), and diarrhea in two (3. 9%). Grade 3 abnormal laboratory data included bilirubinemia in four (7. 8%), GPT elevation in one (2.0%), and hematuria in one (2.0%). In conclusion, combination of CDDP plus oral UFT is efficacious, with low toxicity, in the treatment of advanced NSCLC. In particular, the low hematological toxicity may warrant application of this regimen to the treatment of elderly patients and in trials of concurrent chemoradiotherapy in patients with locally advanced NSCLC.
Lung Cancer
PMID:A phase II trial of oral UFT plus cisplatin (CDDP) in patients with non-small cell lung cancer (NSCLC). 1116 9

BBR 2778 is a novel aza-anthracenedione with no cardiotoxicity in preclinical models. This Phase I dose escalation trial of BBR 2778 was conducted to determine the maximum tolerated dose, the dose-limiting toxicity, and the pharmacokinetic profile of BBR 2778 in patients with advanced solid tumors. BBR 2778 was given in three consecutive weekly 30-min i.v. infusions over a 4-week cycle (cy). Thirty patients (pts) were treated with BBR 2778 at doses ranging from 5 to 150 mg/m2/week. The dose levels 5, 10, 16.5, 25, 37.5, 75, 112.5, and 150 mg/m2/week were investigated in 4 pts (9 cy), 3 pts (3 cy), 3 pts (5 cy), 6 pts (9 cy), 1 pt (1 cy), 4 pts (9 cy), 6 pts (18 cy), and 3 pts (4 cy), respectively. The dose-limiting toxicity was neutropenia, typically occurring at day 14. Other toxicities were mild to moderate and were principally thrombocytopenia, lymphopenia, alopecia, nausea, and vomiting and blue coloration of the skin and urine. No significant cardiac toxicity was observed. The plasma dose concentration curve fitted a biexponential profile, with a rapid distribution phase followed by a prolonged elimination phase (mean t1/2,z, 12 h). BBR 2778 displayed a large volume of distribution (range, 9.7-29.7 l/kg) with a high plasma clearance rate (0.75-1.31 l/h/kg). Less than 10% of the dose was recovered in urine as unchanged drug. The maximum tolerated dose was 150 mg/m2/week for 3 weeks, every 4 weeks. On the basis of this study, the recommended dose for Phase II studies is 112.5 mg/m2/week days 1 and 8 with individual optional administration at day 15, every 4 weeks. Antitumor activity was observed in patients with breast, small cell lung carcinoma, and facial cylindroma. This trial showed that BBR 2778 has a manageable toxicity profile on a weekly schedule. This lead compound of the aza-anthracenedione family shows promising antitumor activity and deserves Phase II investigation in patients with high risk of cumulative cardiotoxicity, such as anthracycline-pretreated breast cancer patients.
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PMID:A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies. 1120 16

The aim of this study was to assess the activity and toxicity of carboplatin/vinorelbine combination chemotherapy in unresectable locally advanced and metastatic non-small cell lung cancer. Between April 1997 and June 1999 30 patients (22 M, eight F, median age 62) received treatment with carboplatin AUC 6 on day 1, and vinorelbine 25mg/m(2) on days 1, 8 and 15. Treatment was given every 28 days for six cycles unless progressive disease occurred. Twenty-three patients (77%) had stage IV disease, and seven (23%) stage IIIB. Ninety-three percent were WHO performance status 0-1. Twenty-three patients were fully assessable. Nine patients achieved partial responses (9/23, 39%) for an overall objective response rate of 9/30 (30%; 95% CI 15-49%). The median duration of response was 2.75 months (range 1-13 months). The median progression-free survival was 2 months and the median survival 5.25 months. The actuarial 1-year survival was 20%. The median number of cycles completed was two (range 1-6). Day 15 vinorelbine was administered in only 18% of cycles. The main toxicity was myelosuppression. WHO grade III/IV neutropenia was experienced in 50% of patients, however, there were only three episodes of febrile neutropenia. Eight patients required blood transfusion and one developed grade III thrombocytopenia. Treatment was ceased in one patient because of grade IV autonomic neuropathy. No patient had significant nausea and vomiting. There were no treatment-related deaths. These results indicate that carboplatin/vinorelbine is well tolerated and has similar activity to cisplatin/vinorelbine in patients with unresectable non-small cell lung cancer, however, the median survival was considerably shorter.
Lung Cancer 2001 May
PMID:Carboplatin and vinorelbine in untreated locally advanced and metastatic non-small cell lung cancer. 1132 88

This phase I study was designed to determine the maximum tolerated dose (MTD) and toxicity of a weekly docetaxel (TXT) and cisplatin (CDDP) combination regimen in advanced non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC who were previously untreated were eligible. Docetaxel, at a starting dose of 20 mg m(-2) per week on days 1, 8 and 15, was combined with a fixed dose of cisplatin 80 mg m(-2) on day 1. Docetaxel was increased in 5 mg m(-2) per week steps. Chemotherapy was given in a 4-weeks cycle. Dose-limiting toxicities (DLTs) were defined as grade 3-4 leukopenia, thrombocytopenia, anemia, fever with grade 4 neutropenia and more than grade 2 non-hematologic toxicity, with the exception of nausea, vomiting, and alopecia. Omission of chemotherapy on day 8 and/or 15 was also considered DLT. Eighteen patients were enrolled in this study. Leukopenia, anemia and fatigue were the DLTs. No grade 4 toxicities were seen in any patients. The overall response rate was 44.4% (95% confidence interval, 21.5-67.4%). The recommended dose of TXT to be combined with CDDP 80 mg m(-2) on day 1 is 35 mg m(-2) per week on days 1, 8 and 15. This is a promising regimen, therefore a multicenter phase II study is now under way.
Lung Cancer 2001 Jul
PMID:A phase I study of weekly docetaxel and cisplatin in advanced non-small cell lung cancer. 1142 97


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