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)

During the past decade, five new cytotoxic drugs have been introduced that are active against non-small-cell lung cancer (NSCLC). These agents include vinorelbine (Navelbine), paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine (Gemzar), and irinotecan (CPT-11, Camptosar). Used alone, these drugs display activity comparable to cisplatin. The combination of cisplatin and one of the newer drugs produces better survival than treatment with cisplatin (Platinol) alone. Randomized studies of chemotherapy regimens that include these newer drugs have demonstrated improved survival, fewer side effects, or both, compared with earlier standard combinations such as cisplatin/vindesine or cisplatin/etoposide. Docetaxel and perhaps some of the other newer drugs are of value for patients previously treated with platinum-containing regimens. Future studies should determine whether combinations of these newer drugs are superior to cisplatin-containing regimens. Although improved survival is the most important factor in defining the best regimen in non-small-cell lung cancer, additional considerations include patient tolerability, costs of administration, and the rationale for and ability to include noncytotoxic agents (such as inhibitors of signal transduction pathwriys or angiogenesis) into the therapeutic program.
 ...
PMID:Rationale for non-platinum chemotherapy in advanced NSCLC. 1149 29

Combination chemotherapy is the cornerstone of treatment that confers a meaningful survival benefit for patients with small-cell lung cancer. However, because there have been no major therapeutic advances for small-cell lung cancer during the last decade, more effective new treatments are necessary to improve the outcome of therapy. Irinotecan (CPT-11, Camptosar), a topoisomerase I inhibitor, is one of the new active agents that provide hope for more effective therapies. In single-agent phase II studies, irinotecan yielded response rates between 16% and 47% in patients with previously treated small-cell lung cancer. A phase II study of irinotecan in combination with cisplatin (Platinol) resulted in a response rate of 86% and a median survival of 13.0 months in patients with extensive-disease small-cell lung cancer. A phase III trial that was conducted by the Japan Clinical Oncology Group (JCOG) clearly demonstrated a survival advantage for the combination of irinotecan and cisplatin vs the standard regimen of etoposide (VP-16, VePesid) and cisplatin. Based on these results, the irinotecan and cisplatin combination is a new standard regimen in the treatment of extensive-disease small-cell lung cancer.
 ...
PMID:Role of topoisomerase I inhibitors in small-cell lung cancer. 1149 34

From December 1994 to July 1997, we conducted a dose escalation study of irinotecan combined with carboplatin in 17 patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum tolerated dose and the dose-limiting toxicities. Irinotecan was administered intravenously over 90 min on days 1, 8 and 15, with carboplatin given at an area under the concentration-time curve dose of 5 mg/ml x min (calculated using Calvert's formula) on day 1. The starting dose of irinotecan was 30 mg/m2 and dose escalation was done in 10-mg/m2 increments. Treatment was repeated at 28-day intervals for at least two cycles. The dose-limiting toxicities were neutropenia and thrombocytopenia, since three out of five patients given 60 mg/m2 of irinotecan developed grade 4 neutropenia and thrombocytopenia. The overall response rate was 35.3%. The median survival time and the 1-year survival rate were 10.5 months and 35.3%, respectively. The maximum tolerated dose of irinotecan with this regimen was 60 mg/m2, while 50 mg/m2 can be recommended for future use. Further studies of this combination in advanced NSCLC are warranted.
 ...
PMID:Dose escalation study of irinotecan combined with carboplatin for advanced non-small-cell lung cancer. 1156 75

Irinotecan (CPT-11) and cisplatin (P) are both active agents against non-small cell lung cancer (NSCLC), and their combination has shown in vitro an additive or synergistic effect. We conducted a phase II study to determine the toxicity and efficacy of their combination as salvage treatment in patients with advanced NSCLC progressing after a docetaxel-based front line regimen. Forty-four patients with histologically confirmed NSCLC were enrolled. The patients' median age was 60.5 years; 39 patients (87%) were male; 38 (86%) had stage IV disease; and 32 (73%) had a performance status (WHO) 0-1. CPT-11 was administered as a 60 min i.v. infusion at a dose of 100 mg/m(2) on day 1 and 110 mg/m(2) on day 8; P was administered at a dose of 80 mg/m(2) on day 8 after CPT-11 administration. Treatment was repeated every 3 weeks. A total of 159 chemotherapy cycles was administered. In an intention-to-treat analysis, nine patients (22; 95% CI: 9.28-34.62%) achieved a partial response (PR), 8 (20%) had stable disease (SD), and 24 (58%) progressive disease (PD). The median duration of response was 4 months, the median time-to-progression (TTP) 8 months, and the median survival for the entire group 8 months. Grade 3-4 neutropenia was observed in 20 (46%) patients and in four cases this was febrile, requiring patient's hospitalisation. Grade 3-4 thrombocytopenia occurred in four (9%) patients. Grade 3-4 diarrhoea was seen in 12 (27%) patients and three of them required hospitalisation. Grade 2-3 neurotoxicity was observed in two (4%) patients and grade 2-3 fatigue in 14 (32%). Other toxicity was mild and no treatment-related death was reported. The combination of CPT-11 and P is a safe, well-tolerated, and active regimen for the treatment of patients with advanced NSCLC previously treated with a docetaxel-based front-line regimen.
Lung Cancer 2001 Dec
PMID:Cisplatin and irinotecan (CPT-11) as second-line treatment in patients with advanced non-small cell lung cancer. 1174 7

Platinum-based chemotherapy is considered to be the standard chemotherapy of non-small cell lung cancer (NSCLC) at present. New agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, topotecan, and amurubicin were developed in the 1990s. Combination chemotherapy using new agents improved survival rates compared with the classic regimen. Irinotecan, paclitaxel, docetaxel, vinorelbine, and gemcitabine have been confirmed to be effective against NSCLC. However, chemotherapy for NSCLC is controversial because the differences in the efficacies of combination chemotherapies including new agents have not been recognized in randomized controlled trials. The Four-Arms Cooperative Study is an ongoing postmarketing clinical trial in Japan. The a ntitumor agents irinotecan, topotecan, paclitaxel, and amurubicin have been confirmed to be effective in small cell lung cancer (SCLC). The combination of etoposide and cisplatin (PE) is the standard regimen for SCLC in Western countries. However, the combination of irinotecan and cisplatin (CP) resulted in higher response rates and better median survival times than PE for extensive-disease SCLC in a JCOG trial. At present, CP is considered to be the standard chemotherapy regimen to treat SCLC in Japan. The development of new agents, particularly molecular target-based drugs and multimodality treatment, is necessary to improve the therapeutic results in lung cancer further.
 ...
PMID:[Developed new agents for lung cancer]. 1190 83

The DNA topoisomerase inhibitor irinotecan (CPT-11, Camptosar) is being evaluated as a novel chemotherapeutic agent that may complement other agents and treatment modalities for small-cell lung cancer (SCLC). Combination chemotherapy is the most effective means of improving the survival of patients with extensive disease, but until recently, no combination demonstrated superior efficacy. In a recent Japanese phase III study, irinotecan in combination with cisplatin significantly improved the survival of previously untreated patients with extensive SCLC compared to standard etoposide/cisplatin therapy (median progression-free survival: 6.9 vs 4.8 months, P = .003; median overall survival: 12.8 vs 9.4 months, P = .002). Two additional phase III trials have been planned in the United States to confirm these results, and to investigate how the administration schedule of irinotecan/cisplatin may be modified to improve its therapeutic index. The results of phase I/II studies have shown that other irinotecan-based combinations demonstrate promising activity in this disease as both first- and second-line therapy. This article reviews the rationale for the use of irinotecan in SCLC, examines key findings from recent clinical studies of irinotecan-based therapy, and discusses how the use of irinotecan in combination with new noncytotoxic anticancer agents can and will be further explored.
 ...
PMID:Irinotecan therapy for small-cell lung cancer. 1201 33

Docetaxel (Taxotere) has shown activity both as a single-agent and in combination with multiple other cytotoxic agents in the front-line therapy of advanced, metastatic non-small-cell lung cancer (NSCLC). A randomized, phase III trial demonstrated a survival advantage for docetaxel over best supportive care in the front-line setting, with docetaxel achieving a 2-year survival of 12% vs 0% for best supportive care. Combinations of docetaxel with the platinum agents have been the most extensively studied in the front-line setting and have produced notably high response rates and encouraging median survivals. When compared to the paclitaxel/cisplatinum combination in a large, phase III randomized trial, the combination of docetaxel and cisplatin resulted in similar response, median survival, and 1-year survival rates. Another randomized phase III trial compared docetaxel/platinum combinations to the US Food and Drug Administration (FDA)-approved vinorelbine (Navelbine)/cisplatin regimen. The docetaxel/cisplatin combination produced a superior overall survival, 2-year survival, and overall response rates compared to vinorelbine/cisplatin. The combination of docetaxel and carboplatin (Paraplatin) demonstrated similar survival and response, and was associated with quality-of-life benefits over the vinorelbine/cisplatin arm. Docetaxel has been successfully combined with gemcitabine in multiple trials with impressive response and survival rates, and an acceptable toxicity profile. A large phase IIb trial demonstrated therapeutic equivalence and lesser toxicities for the docetaxel/gemcitabine combination compared to the combination of docetaxel and cisplatin. The docetaxel/gemcitabine combination therefore represents a viable nonplatinum regimen for first-line treatment of NSCLC. Other combinations that have been tested include docetaxel with vinorelbine, and docetaxel with irinotecan (CPT-11, Camptosar). Docetaxel is active in NSCLC and should be investigated further in combination with novel molecularly targeted drugs such as tyrosine kinase inhibitors, andfarnesyl transferase inhibitors.
 ...
PMID:Docetaxel for locally advanced or metastatic non-small-cell lung cancer. Current data and future directions as front-line therapy. 1210 98

The limited effectiveness of currently available chemotherapy in the treatment of advanced esophageal cancer, and the poor survival achieved in locally advanced disease with combined chemoradiotherapy with or without surgery, have prompted the evaluation of new agents. Irinotecan (CPT-11, Camptosar) has promising single-agent activity in gastrointestinal cancers. In phase II evaluation of weekly irinotecan plus cisplatin, response rates have exceeded 30% in esophageal and gastric cancers. Irinotecan is an active radiosensitizer in preclinical studies and clinical trials in lung cancer. We performed a phase I trial of weekly irinotecan, cisplatin, and concurrent radiotherapy in locally advanced esophageal cancer. Induction chemotherapy with irinotecan and cisplatin was given prior to radiotherapy, over 6 weeks, cycled on a 2-week-on, 1-week-off schedule to relieve dysphagia. Radiotherapy was given subsequently in 180-cGy daily fractions to a total dose of 5,040 cGy. Doses of chemotherapy, when given with concurrent radiotherapy, were cisplatin at 30 mg/m2 followed by irinotecan at escalated doses (40, 50, 65, and 80 mg/m2), on days 1, 8, 22, and 29. Among 18 patients entered in the trial, minimal toxicity has been observed, with no grade 3/4 esophagitis or diarrhea. Hematologic toxicity has been minimal. Dose-limiting toxicity (ie, requiring more than a 2-week delay in radiotherapy) has been seen in one of three patients at the 80-mg/M2 irinotecan dose level, and accrual continues at this dose level. Among 13 evaluable patients, five complete responses have been seen (38%), including three pathologic complete responses in 10 patients undergoing surgery (30%). Asymptomatic pulmonary emboli were noted on the posttreatment computed tomography scan in 3 of 15 patients, prompting the addition of warfarin sodium (Coumadin) prophylaxis on protocol. Full doses of weekly irinotecan (65 mg/ m2) and cisplatin (30 mg/m2) can be combined safely with concurrent radiotherapy in patients with locally advanced esophageal cancer.
 ...
PMID:Irinotecan, cisplatin, and radiation in esophageal cancer. 1210 99

Irinotecan and its active metabolite, SN-38, were reported to have the absorption characteristics of weakly basic drugs. Moreover, stasis of these compounds is thought to induce damage to the intestinal mucous membrane. The purpose of this report was to examine whether oral alkalization (OA) combined with control of defecation (CD) might prevent irinotecan-induced side effects. From day one of irinotecan infusion to day four, OA & CD were practiced using orally administered sodium bicarbonate, magnesium oxide, basic water, and ursodeoxycholic acid. Thirty-two lung cancer patients were treated with irinotecan in combination with cisplatin in the absence of OA & CD (Group A). Thirty-seven patients matched for background characteristics were treated with the same regimen in the presence of OA & CD (Group B). Group B had a reduced incidence of delayed diarrhea (Grade 2 < or = Group A 32.3% vs. Group B 9.4%), nausea, vomiting, and myelotoxicity, especially granulocytopenia compared with Group A. In addition, dose intensification was well-tolerated in Group B. Tumor response rates for non-small cell lung cancer were 59.3% (16/27 patients) in Group B against 38.5% (10/26 patients) in Group A. OA & CD appears to reduce the irinotecan-induced side effects, especially delayed diarrhea. Risk factors statistically associated with delayed diarrhea include advanced age and the use of irinotecan without OA & CD.
 ...
PMID:[A case-control study of prevention of irinotecan-induced diarrhea: the reducing side effects of irinotecan by oral alkalization combined with control of defecation]. 1214 98

The antitumor efficacy of the combination of nedaplatin (NDP) with gemcitabine (GEM) was evaluated against Ma44/GEM, a GEM-refractory subline of Ma44 human lung cancer, which was established by serial in vitro passage of Ma44 cells in the presence of GEM.Ma44/GEM showed less sensitivity to GEM and cytosine arabinoside with resistance factors of 7.7 and 8.3, respectively, but not to Taxol, Irinotecan, Mitomycin C and NDP. Flow cytometry analysis demonstrated that membrane transporter molecules such as multidrug-resistant, multidrug-resistant related protein or lung resistant protein were not induced in Ma44/GEM cells. In vivo experiments confirmed the less sensitivity of Ma44/GEM to GEM. The resistant factor of Ma44/GEM to GEM in vivo was estimated to be 6.7 in terms of ED(50).MA44/GEM-implanted athymic mice were treated with GEM i.v. once followed by i.v. injection of NDP at an interval of approximately 30 min. The mice were treated again with GEM after 3 or 4 days. The combined dosing of NDP with GEM resulted in synergistically enhanced inhibition of tumor growth against Ma44/GEM. The antitumor efficacy of the combination of NDP and GEM was superior to the best effect of either monotherapy. These results demonstrate the effectiveness of the combination of NDP with GEM against the GEM-refractory human lung cancer model.
 ...
PMID:Preclinical combination chemotherapy of nedaplatin with gemcitabine against gemcitabine-refractory human lung cancer. 1217 24


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