Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer activity against several malignant tumors. In this study, as in the Japanese phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous infusion against 10 patients with recurrent colorectal cancer. Median total dose was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung metastases showed a 33.3% response and lymphnode metastases showed a 60% response. However, liver metastases showed no response. The median duration to the onset of partial response was 20 days and the median overall response duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and diarrhea (80%), fever (20%), and general malaise (30%). These were generally well tolerated and reversible. From these results, CPT-11 seemed to become an effective drug for recurrent colorectal cancer. Further trials of combination chemotherapy utilizing CPT-11 seem to be warranted.
 ...
PMID:[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer]. 782 85

As a single agent, irinotecan has demonstrated efficacy in metastatic 5FU resistant colorectal metastatic cancer. Chemotherapy with fluorouracil (5FU) plus leucovorin remains a standard in the treatment of patients with metastatic colorectal cancer. It seemed logical to test the combination of this reference treatment and the new agent. The first trials gave rather disappointing results, suggesting an inhibition of the metabolism of irinotecan into SN38 when 5FU was present in the circulation. More recent studies have given totally different results with a very good tolerance and strong efficacy of the combination of weekly folinic acid + 5FU and irinotecan or LV5FU2 (the so-called de Gramont regimen) and irinotecan. The results were so good that these new schedules are currently developed as first line regimen. Another way to combine 5FU, folinic acid and irinotecan is to alternate a cycle of 5FU, folinic acid and a cycle of irinotecan. Such an alternated schedule has given encouraging results with an objective response rate greater than 30% and a long median survival time (more than 16 months). It is also very easy to combine irinotecan with other drug which have demonstrated activity in the treatment of colorectal cancer. The combinations of irinotecan and mitomycin C or oxaliplatin have given very good results with high objective response rates and good tolerance. Irinotecan plays now an important part in the treatment of metastatic colorectal cancer. This part becomes larger due to the results of the combination trials already presented which have shown strong efficacy and good tolerance.
 ...
PMID:[Irinotecan in combination for colon cancer]. 993 84

Two randomized phase III trials have been conducted in colorectal cancer patients with nonbulky metastatic disease who have failed first-line therapy with 5-fluorouracil (5-FU). In one trial, the use of 350 mg/m2 irinotecan was shown to significantly prolong survival relative to best supportive care. Patients receiving irinotecan also experienced higher quality of life than the controls. In the second trial, the same regimen of irinotecan resulted in a significantly longer median survival than the comparator regimen consisting of best estimated infusional 5-FU. Quality of life was similar across treatments. These two trials were large, well-conducted, and used appropriate methodology for patient selection, measurement of outcome, and statistical analysis. The results of these trials have implications for everyday clinical practice. When appropriate, irinotecan should be offered to patients who have failed 5-FU. Irinotecan should be the reference arm for future studies of investigational second-line drugs; the potential of irinotecan (alone or in combination) in the first-line and adjuvant treatment of colorectal cancer now needs to be evaluated.
 ...
PMID:Comparing irinotecan with best supportive care and infusional 5-fluorouracil: a critical evaluation of the results of two randomized phase III trials. 1021 11

In 1996 two chemotherapy agents were introduced by the U.S. Food and Drug Administration (FDA) with indications for the gastrointestinal malignancies for advanced colon and pancreatic cancers. The agents approved were irinotecan hydrochloride (CAMPTOSAR Injection, Pharmacia & Upjohn Company, Kalamazoo, MI; also investigated under the name CPT-11) for the second-line treatment of metastatic colorectal cancer, recurrent or relapsed, after 5-fluorouracil (5-FU)-based therapy, and gemcitabine hydrochloride (GEMZAR for injection, Eli Lilly and Company, Indianapolis, IN; also referred to as dFdC) for first-line treatment of locally advanced and metastatic cancer of the pancreas. Irinotecan and gemcitabine, with demonstrated activity in colorectal and pancreatic cancer, respectively, are generally well tolerated and can be administered safely on an outpatient basis. Clinically relevant activity is documented for both single agents. Therapy-related side effects are manageable with appropriate monitoring and intervention, and reversible with dose modification or discontinuation. This article is one of a two-part series on new chemotherapeutic agents for gastrointestinal malignancies. The first in the series, this article addresses the agent irinotecan hydrochloride (CAMPTOSAR Injection). The second article, appearing in a subsequent issue, will review gemcitabine hydrochloride (Gemzar for Injection). Both articles review the current clinical use, safety profile, and key patient management guidelines for these new and novel cytotoxics. As clinical and investigational use of irinotecan and gemcitabine increases, the oncology nurse and other members of the health care team will need to anticipate potential treatment associated toxicities and be knowledgeable in their early identification and management. As patient advocates, oncology nurses play a key role in treatment outcome and related quality of life through expert patient education, symptom recognition, and intervention individualized to patient tolerance. This first article of the series addresses irinotecan, which in 1996 was approved for the second-line therapy of metastatic colorectal cancer, recurrent or elapsed, after 5-fluorouracil (5-FU).
 ...
PMID:New agents in gastrointestinal malignancies: Part 1: Irinotecan in clinical practice. 1037 82

This phase I trial combining UFT plus oral calcium folinate (Orzel) with irinotecan (CPT-11) (Camptosar) for the treatment of patients with advanced or metastatic colorectal cancer will open shortly. Eligible patients will have locally advanced or metastatic colorectal cancer, and they may have received adjuvant chemotherapy (provided it has been completed more than 6 months prior to study entry), but will have not received any chemotherapy for advanced or metastatic disease. The primary objectives of this study will be to determine the side-effect profile, dose-limiting toxicities, and the maximum tolerated dose of this combination. A recommended starting dose for future trials will be defined. Response rates will also be observed as a secondary objective. The first cohort of six patients will receive irinotecan 200 mg/m2 by intravenous infusion over 90 minutes on day 1 (the schedule that is in general use in Europe). On days 1 to 14, patients will receive UFT 250 mg/m2/d and calcium folinate 90 mg/d, both divided into three equal doses. This will be followed by a 1-week rest period with treatment for the next cycle resumed on day 22. In subsequent cohorts of six patients, UFT and irinotecan will in turn be escalated provided toxicity is acceptable. The calcium folinate dose will remain fixed at 90 mg/d throughout. The maximum tolerated dose is defined as that at which dose-limiting toxicities occur in more than one third of patients. The cohort of patients treated at the dose below the maximum tolerated dose will be expanded to a total of 20 patients to fully define the pattern of toxicities and activity of the combination.
 ...
PMID:UFT plus calcium folinate/irinotecan in colorectal cancer. 1044 62

The optimal therapy for locally advanced, unresectable, stage III non-small-cell lung cancer (NSCLC) continues to evolve. The critical determinants of overall survival include local tumor control and the eradication of subclinical micrometastatic disease. Historically, standard radiation therapy resulted in a median survival of 7 to 10 months. In a randomized trial, the Cancer and Leukemia Group B (CALGB) established the superiority of induction cisplatin (Platinol) and vinblastine chemotherapy followed by radiation therapy. Additional studies revealed that induction chemotherapy improved survival rates by decreasing metastatic disease progression. Three independent meta-analyses confirmed the survival benefit afforded by cisplatin-based induction chemotherapy followed by radiotherapy, and helped to establish this as the new standard of care. Other investigators have demonstrated improvements in local tumor control and survival with either concurrent chemoradiotherapy or hyperfractionated radiotherapy. Most recently, attention has focused on radiation dose intensity and the utilization of newer, highly active chemotherapeutic agents with concurrent or sequential radiation therapy. These newer drugs, including paclitaxel (Taxol), docetaxel (Taxotere), gemcitabine (Gemzar), vinorelbine (Navelbine), and irinotecan (Camptosar), enhance radiation cytotoxicity and, when administered in systemically active dosages, may also control micrometastatic disease. Phase I and II studies of novel chemoradiation regimens continue to demonstrate encouraging results, and several large randomized clinical trials are currently enrolling patients.
 ...
PMID:Chemoradiation for locally advanced, unresectable NSCLC. New standard of care, emerging strategies. 1049 43

Irinotecan is active as a single agent in advanced non-small cell lung cancer (NSCLC), with overall response rates (ORRs) of 13-32% reported in phase II trials. In the first-line treatment of stage III/IV NSCLC, phase II studies have suggested that the combination of irinotecan with cisplatin can achieve response rates of 29-75%, which is greater than achieved with older platinum-containing combinations. Neutropenia and diarrhea are the dose-limiting toxicities. In small cell lung cancer (SCLC), irinotecan alone has achieved ORRs of 16-47% in previously treated SCLC, which is higher than expected with oral etoposide. Studies with irinotecan in combination with cisplatin or etoposide have reported responses of up to 79%. Irinotecan is active in cervical cancer patients whose metastases are outside the area of previous irradiation (ORR 24%) and a major phase II/III study is currently comparing irinotecan as single agent or in combination with cisplatin against a reference cisplatin arm.
 ...
PMID:Irinotecan in cancers of the lung and cervix. 1063 Mar 63

This phase I/II nonrandomized, open-label study was designed to assess the safety and benefit of sequencing irinotecan (Camptosar, CPT-11) plus paclitaxel (Taxol) immediately after cisplatin (Platinol)/etoposide (VePesid, VP-16) or carboplatin (Paraplatin)/etoposide in patients with extensive small-cell lung cancer (SCLC). Ten patients were evaluable in phase I; all had previously been treated with cisplatin and etoposide, and five of the 10 had also previously received carboplatin and paclitaxel. All 10 patients were given a fixed dose of irinotecan (60 mg/m2) and escalating doses of paclitaxel weekly for 3 weeks. Three patients had grade 4 toxicities, one at the lowest dose level of paclitaxel (15 mg/m2). Two patients had grade 3 toxicities. The dose-limiting toxicity occurred at the 60 mg/m2 paclitaxel dose level, when the performance status of both patients in that group decreased to 60 (Karnofsky scale). Two patients had progressive disease after 1 month of treatment and did not receive cycle 2. Three of seven patients evaluable for response had complete remissions. A fourth patient had resolution of lymphangitic metastases and resolution of a partial small bowel obstruction but did not have measurable disease. The fifth patient had a partial remission. The ongoing phase II portion of the study is restricted to previously untreated patients who will receive at least one cycle of either cisplatin or carboplatin in combination with etoposide followed by irinotecan at 60 mg/m2 and paclitaxel at 50 mg/m2 dosed once weekly for 3 weeks.
 ...
PMID:Phase I/II study of weekly irinotecan and paclitaxel in patients with SCLC. 1098 Dec 93

Fluorouracil has been the mainstay of treatment for colorectal cancer (CRC) for almost 40 years. Various schedules and biochemical modulators have been investigated in an attempt to improve the therapeutic efficacy of fluorouracil. To date, fluorouracil plus folinic acid represents the standard therapy in CRC for the adjuvant treatment of patients at high risk for relapse and for the first-line treatment of metastatic disease. To gain clinical acceptance, however, oral fluoropyrimidines must confer at least the same survival advantages associated with the optimal intravenous fluorouracil regimens. Irinotecan and oxaliplatin are 2 other novel agents that have mechanisms of action that are uniquely different from those of fluorouracil, with demonstrated activity in patients with fluorouracil-refractory disease. Recent randomised trials comparing fluorouracil plus folinic acid with combinations of either irinotecan or oxaliplatin and fluorouracil plus folinic acid have shown that response rates are improved and time to progression is increased in patients receiving the combination regimens. These regimens are being rapidly introduced in the adjuvant setting, and the role and acceptance of these combination regimens as first-line therapy needs to be defined. Other novel agents being evaluated in the treatment of patients with advanced CRC include oral edrecolomab (monoclonal antibody 17-1A) and tumour vaccines. Future research is focused on enabling clinicians to individualise treatment strategies in patients with CRC, so as to improve clinical outcomes and reduce drug toxicity.
 ...
PMID:Progress in colorectal cancer chemotherapy: how far have we come, how far to go? 1104 19

Irinotecan (CPT11) has established activity in the treatment of advanced colorectal cancer without cross-resistance with established 5-fluorouracil/folinic acid-based therapy. This phase II study was conducted to establish the efficacy and tolerance of combination treatment with irinotecan and 5-fluorouracil as salvage treatment for this disease. Open phase II trial of CPT11 180 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and 5-fluorouracil 400 mg/m2 loading dose followed by 600 mg/m2 infusion on days 1 and 2. Treatment was continued until progression or limiting toxicity. Responders could proceed to surgical resection of residual disease. Thirty-nine patients from 2 institutions received a total of 287 cycles of therapy (median 7 cycles/patient). Eight patients achieved an objective response (7 for liver metastasis and 1 for lung metastasis), and an additional 12 obtained stabilization of disease or minor responses (MR); of these patients, 8 with liver metastasis (7 partial response and 1 MR) underwent hepatic resection of metastases and all them obtained a complete response. The median duration of response was 14 months, and the median survival was 11 months. Hematologic toxicity (neutropenia) was the most common serious side effect (29% of patients in 2% of cycles), but significant fever developed in only 4 patients. Grade III diarrhea was experienced in at least 1 cycle by 10% of patients. The results of this schedule compare favorably with previously reported experience of a phase I study designed to establish the dose of CPT11. Efficacy in this poor prognosis group of patients is very encouraging, and the schedule is well tolerated by even previously treated patients.
 ...
PMID:Prospective phase II trial of iriontecan, 5-fluorouracil, and leucovorin in combination as salvage therapy for advanced colorectal cancer. 1123 43


1 2 3 4 5 6 Next >>