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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Role of topoisomerase I inhibitors in small-cell lung cancer. 1149 34

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

Reverse transcription polymerase chain reaction (RT-PCR) single-strand conformation polymorphism analysis was used to detect topoisomerase I (top1) mutations in total RNA from 16 specimens that were excised during surgery from eight patients with non-small cell lung cancer (NSCLC) who had received preoperative chemotherapy consisting of irinotecan (CPT-11) and cisplatin. PCR single-strand conformation polymorphism and subsequent DNA sequencing analysis showed two nucleotide substitutions resulting in Trp736stop (TGG to TGA) and Gly737Ser (GGT to AGT) in one tumor specimen. The mutations were located near a site in top1 that was previously reported to harbor a mutation in the human lung cancer cell line PC7/CPT, which was selected for CPT resistance. These results demonstrate that mutations in top1 occur after chemotherapy with CPT-11 in NSCLC patients and suggest that development of resistance to CPT-11 in some patients may involve mutation of top1. However, the significance of top1 mutations to CPT resistance needs to be further investigated.
Lung Cancer 2002 Mar
PMID:Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan. 1184 5

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

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.
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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.
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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.
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PMID:Irinotecan, cisplatin, and radiation in esophageal cancer. 1210 99

Based on the synergistic cytotoxicity demonstrated in vitro by topoisomerase I inhibitors followed by docetaxel and the feasibility of giving both drugs on a weekly schedule avoiding overlapping toxicities, we designed a phase I trial of weekly CPT-11 (irinotecan)/docetaxel to determine the dose-limiting toxicities (DLT) and the maximum-tolerated dose (MTD) of this combination. Eighteen patients with advanced solid tumors treated with at least one prior chemotherapy regimen were included in this trial. CPT-11 was administered as a 90-min (intravenous) IV infusion followed immediately by docetaxel as a 30-min IV infusion. Both drugs were given on days 1, 8 and 15 in 4-week cycles. Four escalating dose levels of CPT-11/docetaxel (level I: 60/20 mg/m(2), level II: 60/25 mg/m(2), level III: 70/25 mg/m(2), and level IV: 70/30 mg/m(2)) were studied. Forty-seven cycles were administered (range, 1-5 courses) with a median number of 2.6 cycles per patient. Grade 4 leukopenia was the DLT reached at dose-level IV (CPT-11/docetaxel 70/30 mg/m(2)). Four patients had grade 3 anemia at dose levels III (two patients) and IV (two patients), while grade 3/4 thrombocytopenia was not seen. Grade 3/4 non-hematologic toxicities included grade 3 diarrhea in two patients (dose levels II and IV), grade 3 asthenia in one patient (dose level II) and grade 3 stomatitis in one patient (dose level I). The recommended dose of this weekly schedule is CPT-11 70 mg/m(2) and docetaxel 25 mg/m(2). DLT of this regimen is leukopenia, although toxicity is manageable at the recommended dose level. The activity of this regimen is being evaluated in a phase II study in previously treated patients with advanced non-small cell lung cancer.
Lung Cancer 2002 Aug
PMID:Phase I study of weekly CPT-11 (irinotecan)/docetaxel in patients with advanced solid tumors. 1214 Jan 45

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

Lung cancer is the leading cause of cancer-related death in the United States. There was rapidprogress in the treatment of lung cancer duringpast decades, but local control and survival rates are still poor. Radiation therapy has been an indispensable part of the management of lung cancer, and a recent paradigm is concurrent chemoradiation therapy. Many novel chemotherapeutic agents were recently developed to improve both local and systemic control of cancer, including camptothecin derivatives, which are topoisomerase I inhibitors. Irinotecan (CPT-11, Camptosar) is a semisynthetic water-soluble derivative of camptothecin. Irinotecan is active as a single agent against lung cancer, and is also a potent radiosensitizing agent in human lung cancer cell lines and xenografts. There have been many phase I and II clinical trials demonstrating promising results of single-agent irinotecan and combination with concurrent therapy. This article reviews irinotecan's mechanism of action of cytotoxicity and of radiation-sensitizing effects, as well as recent clinical data regarding combining radiation therapy and irinotecan for both non-small-cell and small-cell lung cancer.
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PMID:Irinotecan in combination with radiation therapy for small-cell and non-small-cell lung cancer. 1237 96


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