Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Strategies for identifying patients at high risk of chemotherapy-induced neutropenia are reviewed. Among lung cancer patients, a 24% rate of neutropenia has been reported. This rate is below the 40% threshold recommended by the American Society of Clinical Oncology (ASCO) for the prophylactic use of colony-stimulating factors. Risk factors for febrile neutropenia in patients receiving adjuvant chemotherapy for breast cancer include older age, fluorouracil-containing regimens, bone marrow involvement or prior myelosuppressive therapy, and concomitant or prior radiation therapy. According to the Silber predictive model, factors suggesting a high risk of hospitalization for febrile neutropenia include the absolute neutrophil count during the neutrophil nadir in cycle 1 of chemotherapy. Patients with non-Hodgkin's lymphoma (NHL) are at risk of febrile neutropenia and fall on the edge of the ASCO guidelines. Risk factors in NHL patients include certain combination chemotherapy regimens, an albumin concentration of > 3.5 g/dL, an above-normal lactate dehydrogenase concentration, bone marrow involvement, age of > 65 years, and renal disease. Patients can be stratified into low-risk and high-risk categories for febrile neutropenia. High risk is associated with a duration of neutropenia of more than seven days and concomitant medical conditions, such as hypotension and diarrhea. A majority of low-risk patients can be managed as outpatients. Prophylactic use of colony-stimulating factors is currently believed not to be cost-effective if the frequency of febrile neutropenia is less than about 20% for a given treatment regimen. Patients at higher risk of febrile neutropenia in association with cancer chemotherapy may include the elderly and those with specific malignancies and prior neutropenic events, as well as those receiving combination chemotherapy and radiation therapy.
 ...
PMID:Identification of cancer patients at high risk of febrile neutropenia. 1216 33

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50 mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min, intravenously on days 1, 8, 15). All patients were assessable for toxicity and survival; 28 patients were assessable for response. There were nine partial responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median time to progression was 3.5 months. Median survival time was 6.1 months. Major toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed in 7%. There was one treatment-related death due to febrile neutropenia and sepsis. This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer.
Lung Cancer 2002 Sep
PMID:Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer. 1223 2

The purpose of this study was to evaluate the efficacy and tolerance of combined irinotecan and vinorelbine in previously treated patients with stage IIIB and IV non-small-cell lung cancer (NSCLC). Thirty-three patients with NSCLC (7 stage IIIB and 26 stage IV) were enrolled. All had been previously treated with cisplatin, paclitaxel, and gemcitabine as first-line chemotherapy. In addition, 24 patients had received radiotherapy. Irinotecan (300 mg/m(2)) was administered on day 1 and vinorelbine (30 mg/m(2)) on days 1 and 14, every 4 weeks. Partial response was achieved in 3 patients (9%; 95% CI: 2-24%), stable disease (SD) in 13 (39%; 95% CI: 23-58%), whereas 17 patients progressed (51%; 95% CI: 33-69%). Median event-free survival was 10 weeks and median overall survival was 25 weeks. Three patients were event free at the end of the study with a follow-up of 40, 73, and 75 weeks. Toxicity was mild, with leukopenia grade III-IV in 8.6% of cycles. No episodes of diarrhea III-IV were observed. Three patients died early after administration of this combination, one of them in the context of severe leukopenia and thrombocytopenia. Approximately 50% of patients treated with CPT-11 and vinorelbine in combination show partial response or stable disease with minimal toxicity.
 ...
PMID:Second-line chemotherapy with irinotecan and vinorelbine in stage IIIB and IV non-small-cell lung cancer: a phase II study. 1239 89

Recent experience with weekly administration of docetaxel has demonstrated less myelotoxicity and suggested that this regimen holds promise for elderly patients at the high risk of myelosuppression. However, in this phase I trial of weekly docetaxel conducted only in elderly patients (70 years old or more) with non-small cell lung cancer (NSCLC), the toxicity profile was markedly different from that in previous reports. The dose-limiting toxicities were neutropenia, diarrhea and infection, all of which were observed at a dose of 30 mg/m(2)/week and the maximum-tolerated dose by protocol definition was 30 mg/m(2)/week. Although other hematological and non-hematological toxicities observed in this treatment were generally moderate and were well tolerated by elderly patients with NSCLC, the risk of myelosuppression still requires careful attention.
Lung Cancer 2002 Nov
PMID:Phase I trial of weekly docetaxel in elderly patients with non-small cell lung cancer. 1239 34

The notification rate of tuberculosis in Japan was 31.0 per 100,000 in 2000. The rate was especially high among the elderly population, reaching 85.5 per 100,000 among those over 65 years of age. We conducted a study of preventive therapy in middle-aged and elderly persons selected from the population-based screening by the mass miniature radiography. The eligible criteria were 50-79 years of age, fibrous lesion which were compatible with healed tuberculosis and showed no change for at least one year, no previous treatment for tuberculosis, normal liver function tests, and no serious disease at the time of study. The eligible criteria for liver function tests in this study was less than 50 IU/L of AST and ALT value, and less than 1.5 mg/dl of T-bil level. A total of 13,219 people underwent TB screening in 4 cities in 1997 and 2 cities in 1998. Among them, 440 persons fulfilled the above criteria based on the screening records and chest X-ray films. The municipal offices sent letters to 418 people, except 22 whose addresses were unknown, to obtain permission to use their addresses and results of screening in our study. Permission was obtained from 137 persons and we sent them invitation letters for cost-free physical checkup service. Ninety-five persons visited us, and we offered them physical checkup and explained about our study. After obtaining the informed consent, we performed chest X-ray and sputum examination for 3 consecutive days. Finally 29 people were enrolled in the study. They were divided into 4 groups by sex and age, and were randomly assigned to one of two treatment groups. One group took 300 mg of INH per day for 6 months and the other group was only followed up by chest X-ray. Fourteen out of 29 persons began to take INH and received monthly liver function test. All the subjects were scheduled to follow by medical checkup every 6 months for 5 years. The proportion of taking INH tablets was estimated to range from 94% to 100%, based on the calendar for record of taking medication and the number of remaining tablets each month. Six (42.9%) of 14 persons reported adverse reactions. Two of 6 persons complained some of diarrhea, vomiting and gastrointestinal disturbance within 2 weeks, and discontinued taking INH, although none of them showed abnormal liver function tests. Two of 6 persons who reported some kinds of symptoms and 2 of 8 persons who did not complain of any symptoms showed abnormal liver function tests. The abnormal liver function tests had developed from 2 months after the beginning of INH taking in most of the persons and the abnormality improved after the completion of 6-month treatment. We have followed them for a maximum duration of 2.5 years, and 3 cases dropped out from the study. These defaulted cases had completed 6 months of INH. One person (69 y.o. male) was diagnosed as active TB by his chest X-ray film at the 6th month medical checkup, although it was not confirmed bacteriologically. One person (62 y.o. female) had the mastectomy for breast cancer 7 months before the entry to this study and relapsed at the 8th month after the entry. One person (73 y.o. female) was diagnosed as lung cancer at the medical checkup on 2.5 years. Besides them, 4 persons were suspected of worsening the abnormal shadows on chest X-ray films; one was from the INH group and three were from the follow-up group. However none of them was diagnosed clinically and bacteriologically as active tuberculosis.
 ...
PMID:[Preventive therapy in middle-aged and elderly persons selected from the population-based screening by mass miniature radiography--methodological aspect and adverse reactions]. 1244 Jan 39

A phase II study was conducted to assess the activity and toxicity of irinotecan (CPT-11) and carboplatin (CBDCA) combination chemotherapy for advanced non-small-cell lung cancer (NSCLC). Eligibility included chemo-naive advanced NSCLC patients with measurable disease and a good performance status. CPT-11 of 50 mg/m(2) was administered as a 90-min intravenous infusion on days 1, 8, and 15. CBDCA dosed to an area under the concentration-time curve of 5 mgmin/ml, using Calvert's formula, was administered by 90-min infusion after the CPT-11 infusion on day 1. Treatment was repeated 28 days interval for at least two cycles. Haematopoietic growth factors were not routinely used. From December 1997 to January 1999, 36 patients were entered into the study. The overall response rate was 25.0% (95% confidence interval: 12.1-42.2%). The median survival time and the 1-year survival rate were 10.2 months and 42.2%, respectively. Major toxicity by Japan Clinical Oncology Group criteria was as follows: grade 3-4 neutropenia 76.5%; grade 3 anemia 26.5%; grade 3/4 thrombocytopenia 47.1%; grade 3 nausea/vomiting 36.1%; grade 3-4 diarrhoea 5.9%; grade 3 alopecia 5.9%; grade 3-4 skin rush 2.9%. Four patients developed febrile neutropenia and only one had serious diarrhea induced by CPT-11. Actual relative delivery dose of CPT-11 to the projected one on days 8 and 15 were 0.86 and 0.43, respectively. It seemed that CPT-11 and CBDCA was more toxic regimen than CPT-11 and CDDP in advanced NSCLC. The relatively disappointing response rate could be related with low dose intensity of CPT-11.
Lung Cancer 2002 Dec
PMID:Phase II study of irinotecan and carboplatin for advanced non-small cell lung cancer. 1244 53

In previously untreated patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) the combination of docetaxel and gemcitabine is active and well tolerated. In the phase II setting using a 3-week schedule, response rates (RR) ranged from 25 to 50%, and median survival from 11 to 13 months. Preliminary data with weekly and bi-weekly schedules indicate maintained efficacy while reducing the risk of neutropenia. A randomized phase III trial has shown that the combination of docetaxel and gemcitabine is as active as docetaxel plus cisplatin, achieving a 1-year survival rate of 39%, with significantly less neutropenia and gastro-intestinal toxicity. The combination of docetaxel with vinorelbine is equally active and the associated toxicities are manageable. In phase II studies the average response rate is 40%, and in one study using a 2-week schedule the 1-year survival rate was 60%. With this combination neutropenia is the commonest adverse event while clinically significant neuropathy is infrequent. In a randomized phase II trial, docetaxel plus cisplatin was compared to docetaxel plus irinotecan. The non-platinum doublet achieved comparable levels of activity, though with a different toxicity profile (more diarrhea but less nausea and vomiting). The combination of docetaxel with irinotecan and carboplatin has achieved 1-year survival of 55%. All three docetaxel combinations (gemcitabine, vinorelbine, and irinotecan) could provide a valuable alternative to platinum-based chemotherapy and should be further evaluated in phase III setting.
Lung Cancer 2002 Dec
PMID:Challenging the platinum combinations in the chemotherapy of NSCLC. 1248 Jan 91

To determine a standard combination chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), we conducted a phase III trial of irinotecan (CPT-11) to test the hypotheses that CPT-11+cisplatin is superior to cisplatin+vindesine and that CPT-11 monotherapy is not inferior to cisplatin+vindesine. A total of 398 patients with previously untreated NSCLC were randomised to receive cisplatin+CPT-11 (CPT-P), cisplatin+vindesine (VDS-P) or CPT-11 alone (CPT). In the CPT-P arm, CPT-11 60 mg m(-2) was administered on days 1, 8 and 15, and cisplatin 80 mg m(-2) was administered on day 1. In the VDS-P arm, cisplatin 80 mg m(-2) was administered on day 1, and vindesine 3 mg m(-2) was administered on days 1, 8 and 15. In the CPT arm, CPT-11 100 mg m(-2) was administered on days 1, 8 and 15. The median survival time was 50.0 weeks for patients on CPT-P, 45.6 weeks for those on VDS-P and 46.0 weeks for those on CPT (P=0.115, CPT-P vs VDS-P; P=0.089, CPT vs VDS-P), and the hazard ratio was 0.85 (95% confidence interval (CI): 0.65-1.11) for CPT-P vs VDS-P and 0.83 (0.64-1.09) for CPT vs VDS-P. The response rate was 43.7% for patients on CPT-P, 31.7% for those on VDS-P and 20.5% for those on CPT. Major adverse reactions were grade 4 neutropenia observed in 37, 54 and 8% of the patients on CPT-P, VDS-P and CPT, respectively; and grades 3 and 4 diarrhoea observed in 12, 3 and 15% of the patients, respectively. CPT-P therapy produces comparable survival to VDS-P in patients with advanced NSCLC. CPT-11 monotherapy is not inferior to VDS-P in terms of survival. The CPT-11-containing regimen is one of the most efficacious and well tolerated in the treatment of advanced NSCLC.
 ...
PMID:Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. 1256 73

A phase II multicentre study of a 3-week schedule of irinotecan (CPT-11) and cisplatin providing the highest recommended dose intensity of both agents in combination, was conducted in patients with advanced non-small cell lung cancer (NSCLC). Seventy-four stage IIIB (not suitable for radiotherapy) or stage IV NSCLC patients were enrolled to receive CPT-11 200 mg/m(2) i.v. and cisplatin 80 mg/m(2) i.v. on day 1 every 3 weeks. Relative dose-intensities for CPT-11 and cisplatin were 92 and 95%, respectively. No complete responses were observed. Twenty-five patients out of 73 obtained a partial response (34.2%). Partial responses were confirmed in 18 patients (24.7%: 95% CI, 15.3-36.1%). Median survival overall was 8.2 months, 9.7 months for patients with baseline performance status (PS) 0 and 1, and 4 months for patients with PS 2. The 1-year survival rate was 31%. Major clinical toxicities were grade 3 and 4 delayed diarrhoea (29% of patients) and febrile neutropenia (14% of patients). In conclusion, the present once-every-3-week schedule of CPT-11 and cisplatin is feasible and active in PS 0-1 advanced NSCLC patients, but results do not seem superior to those reported with other schedules.
Lung Cancer 2003 Feb
PMID:Three-week schedule of irinotecan and cisplatin in advanced non-small cell lung cancer: a multicentre phase II study. 1258 74

Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.
 ...
PMID:Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507. 1264 14


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