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

The antimetastatic effect of a new water-soluble derivative of camptothecin, 7-ethyl-10-(4-(1-piperidino)-1-piperidino) carbonyloxy-camptothecin (CPT-11), were examined in several metastatic murine tumor systems. Intravenous (i.v.) injection of CPT-11 into BALB/c mice inhibited lung metastasis by i.v. inoculated, metastatic colonic adenocarcinoma 26 (C26) cells, C26NL-17, in BALB/c mice. This treatment was also effective in C57BL/6 mice against lung metastasis by i.v. inoculated B16-F10 and B16-BL6 cells, highly metastatic variants of the B16 melanoma. Furthermore, intraperitoneal (i.p.) injection of CPT-11 significantly inhibited the growth of C26NL-22 cells, a highly metastatic variant of C26, inoculated subcutaneously (s.c.) into the left front footpads of BALB/c mice. Also, i.p. or i.v. injection of CPT-11 effectively inhibited the growth of 3LL tumors inoculated s.c. into the hind footpads of C57BL/6 mice. Moreover, following s.c. inoculation of either C26NL-22 or 3LL cells, combined surgical excision of the primary tumor and either i.p. or i.v. CPT-11 injections given before or after surgery markedly inhibited the formation of pulmonary metastases. These results show that a new derivative of camptothecin, CPT-11, has a potent inhibitory effect against both spontaneous and experimental lung metastasis.
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PMID:Inhibition of spontaneous and experimental metastasis by a new derivative of camptothecin, CPT-11, in mice. 337 Jul 38

In recent years, the incidence of endometrial cancer has tended to increase gradually in Japan. Most cases (early cancer of stage I and II) are treated by hysterectomy alone, and the prognosis has been relatively good. From analysis of the poor prognostic factors in endometrial cancer, we understood that additional therapy is necessary for patients who have the following factors: degree of differentiation: G3; invasion to > 1/2 myometrium; metastases to pelvic or para-aortic lymph node, isthumus-cervix extension; surgical stage III and more. However, for patients with advanced inoperable and recurrent cancer, a radiotherapy, is not so sensitive to endometrial cancer has been used. A first line establish a chemotherapy has not been established either. Various attempts have been made to establish a chemotherapy for endometrial cancer. As a result, adriamycin (ADR) and cisplatin (CDDP) have proved effective as single agents. For patients with early cancer who have the poor prognostic factors mentional above, irradiation and polychemotherapy regimens (CAP and AP) are effective. Since the progression of endometrial cancer is dependent on sex steroid hormones, antitumor effects of Medroxyprogesterone acetate (MPA) are expected to be effective for patients with estrogen receptor (ER) positive and progesterone receptor (PR) positive cancer, or with well-differentiated adenocarcinoma (G1 type) histologically. Although several forms of therapy are capable of inducing objective remission as adjuvant treatment, all treatment for advanced and recurrent disease remains palliative, and responses and survival for patients treated with irradiation and chemotherapy remain short. Furthermore, we should examine new methods such as new drug application of key drugs like ADR and Pt pharmaceutical preparation, improvement of Dose intensity of the key drugs and Biochemical modulation, CPT-11, Taxol and assembly of key drugs, along with the Circadian approach in the light of Biochronology.
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PMID:[Chemotherapy of uterine endometrial cancer]. 766 68

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.
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PMID:[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer]. 782 85

The projected cure rate for patients who develop lung cancer in 1993 is only 13%. The majority of these patients have metastatic disease at the time of diagnosis, and are therefore ineligible for curative surgery. Among the minority of patients who undergo surgical therapy with curative intent, the majority experience relapse in metastatic sites. Patients with metastatic disease cannot be cured with currently available therapies. Recent randomized studies suggest that cisplatin-based chemotherapy regimens can prolong survival in patients with metastatic non-small cell lung cancer and small cell lung cancer. It was thus logical to evaluate cisplatin-based chemotherapy in early disease stages. Many randomized studies have compared radiation therapy alone with radiation plus cisplatin-based chemotherapy in locally advanced, inoperable, stages IIIA and IIIB non-small cell lung cancer. Most, but not all, of these studies show a survival benefit for the combined-modality approach. Although the improvement in median length of survival in these studies is modest, long-term survival rates are often doubled or tripled. The optimal chemoradiotherapy combination is unknown. Fewer randomized trials have evaluated cisplatin-based chemotherapy as an adjuvant to surgery in operable stages I through IIIA disease. A trial of the Lung Cancer Study Group comparing postoperative cyclophosphamide/doxorubicin/cisplatin with immunotherapy in stages II and IIIA adenocarcinoma and large cell carcinoma showed a small survival advantage for the chemotherapy. A European postoperative randomized study comparing cisplatin-based chemotherapy with no therapy also showed a survival advantage for chemotherapy, as did a small ongoing study from M.D. Anderson Cancer Center (Houston, TX) with preoperative chemotherapy. However, there are many negative randomized studies evaluating postoperative chemotherapy, especially with non-cisplatin-based regimens, and further studies are obviously needed. Many new agents have produced exciting preliminary results. Response rates in excess of 20% were reported for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), irinotecan (CPT-11), topotecan, and gemcitabine. Studies in the next few years will help to define the ultimate role of these agents. Further developments in understanding the biology (and molecular biology) of lung cancer are leading to preclinical studies of antigrowth factors and genetic therapy.
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PMID:The treatment of non-small cell lung cancer: current perspectives and controversies, future directions. 805 74

A late phase II study of CPT-11 for advanced breast cancer was conducted at 27 institutions. Seventy-nine patients were enrolled, 75 were eligible for the study, and 65 were evaluable for efficacy. One complete response and 14 partial responses were obtained, and the response rate was 23%. The response rate of patients with prior endocrine therapy and prior chemotherapy including adriamycin or other anthracycline drugs was 27% (11/41) and 26% (12/46), respectively. The response rate for patients with estrogen receptor-negative tumors and premenopausal patients was 32% (6/19) and 27% (4/15), respectively. Responses were observed not only for soft tissue lesions such as lymph nodes (5/17), but also for distant metastases in the lungs (8/28) and bone (1/18). The major adverse reactions were myelosuppression and gastrointestinal symptoms. The incidence of Grade 2 or higher leukopenia, anemia, nausea/vomiting, anorexia, diarrhea and alopecia was 68%, 31%, 67%, 59%, 37%, and 30%, respectively. These results suggested that CPT-11 was a promising drug for advanced breast cancer.
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PMID:[A late phase II study of CPT-11 (irinotecan) in advanced breast cancer. CPT-11 Study Group on Breast Cancer]. 821 Feb 51

Colorectal cancer affects around 5% of the population in Westernised countries and is associated with a high level of morbidity and mortality. Overall, around 50% of patients can expect to be fully cured by surgery, along with recent improvements in survival due to the use of adjuvant therapy. However, in patients who develop metastatic disease, the prognosis is poor, and the appropriateness of anticancer chemotherapy in such patients has been controversial. Nevertheless, there is increasing evidence that chemotherapy can extend life expectancy in colorectal cancer and that in metastatic disease patients achieve a significant benefit from early rather than late chemotherapy. For first-line treatment of metastatic colorectal cancer, the best available regimens have been those which include 5-fluorouracil (5-FU) and folinic acid; a meta-analysis of nine randomised clinical studies of such regimens produced a mean response rate of 23%. However, in those who fail or relapse, there has been no established second-line alternative. The development of CPT-11 (Campto, irinotecan), a specific inhibitor of topoisomerase I, represents a significant advance in the management of colorectal cancer. Following encouraging observations of sustained activity in colon cancer cell lines, including those having the MDR phenotype, clinical studies of CPT-11 monotherapy in both chemotherapy-naive and pretreated patients with advanced colorectal cancer demonstrated response rates at least equivalent to those achieved with first-line 5-FU/folinic acid combination therapy. This indicates that CPT-11 does not exhibit cross-resistance with 5-FU, making it the first effective second-line agent in this setting. Further studies are ongoing to define the optimum dosage schedule for CPT-11 and to assess the utility of CPT-11 as a single agent in second-line therapy, or combined with 5-FU and other anticancer agents as first-line therapy. In conclusion, CPT-11 offers a different cytotoxic approach that may complement the use of 5-FU/folinic acid in colorectal cancer in the future.
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PMID:Current status of colorectal cancer: CPT-11 (irinotecan), a therapeutic innovation. 894 58

The efficacy of CPT-11 (Campto, irinotecan) given as a single agent has been assessed in three phase II clinical studies of patients with advanced colorectal cancer conducted in Japan, Europe and the U.S. Among a total of 337 evaluable patients treated with CPT-11 in dosage schedules of 100-150 mg/m2 weekly or bi-weekly (Japan, n = 63; U.S., n = 118) or 350 mg/m2 every 3 weeks (Europe, n = 156), overall objective response rates ranged from 17 to 27% and the median duration of response was approximately 7-9 months. Prior treatment with chemotherapy did not preclude a response to CPT-11 as evidenced by response rates of 14 to 22% and response durations of approximately 6-8 months in this cohort. In the European study, comparison of chemotherapy-naive patients with those who had received only one 5-fluorouracil (5-FU)-based regimen revealed similar response rates (22 and 20%) and of note, CPT-11 maintained its activity in pretreated patients who had previously experienced progressive disease. Together, these results suggest a lack of cross-resistance between the two agents. Leucopenia and delayed diarrhoea were the major adverse events observed in these studies, with grade 3-4 events occurring in 15-36% and 13-47% of patients, respectively. CPT-11, therefore, has significant activity in advanced colorectal cancer with response rates that are reproducible, durable and comparable to those achieved with 5-FU plus folinic acid in the first-line treatment of metastatic disease. Further work is needed to define the optimum dosage schedule for CPT-11 and also to assess fully the utility of CPT-11 in combination with other chemotherapeutic agents. Nevertheless, the activity of CPT-11 in patients refractory to treatment with 5-FU may be considered a significant advance, making it the first effective second-line agent in this setting.
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PMID:Efficacy of CPT-11 (irinotecan) as a single agent in metastatic colorectal cancer. 894 60

Over the past year, several new anticancer agents have entered the clinic and are undergoing further phase II clinical development at the time of this writing. There has been a sudden influx of rationally designed drugs with novel therapeutic effects ranging from direct cellular toxicity to inhibition of blood vessel formation and of metastases. This review focuses only on cytotoxic drugs that have been in clinical development for the past 5 years; however, only recently have these drugs found a "niche" in the clinic. These drugs include novel taxanes (eg, docetaxel), the camptothecin analogues (eg, irinotecan [CPT-11]), the newer generation of thymidylate synthase inhibitors (eg, raltitrexed [ZD 1694, Tomudex]), nucleoside analogues (eg, gemcitabine), and oral alternatives to intravenous 5-fluorouracil. Most of these agents have completed or have entered phase II or III testing, and the results of these trials will be available to us over the next few years.
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PMID:Promising new agents in oncologic treatment. 897 73

Colorectal cancer is one of the most frequent cancers in western countries. Five years after curative surgery and adjuvant chemotherapy, about 10% more patients with Dukes C colon cancer are free of disease compared to the control group. Several regimens using 5-fluorouracil with folinic acid (5FU/FA) or levamisole are available. For patients with disseminated disease. 5FU/FA based treatments allows a doubling in survival as compared to best supportive care. Moreover, quality of life is significantly improved. New agents are upcoming. Tomudex seems to be equivalent to 5FU/FA but easier to administer. CPT-11 or oxaliplatin have been investigated in second line after failure of 5FU/FA. The available data suggest that median survival is prolonged by ten months, in addition to what was already obtained in first line with 5FU/FA. Colorectal cancer must be revisited. An active approach of our patients should allow to reduce the incidence of the disease, to increase the number of disease free patients 5 years after surgery, to prolong survival and improve the quality of life of those who will develop metastatic disease.
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PMID:[Colorectal cancer: a controllable disease]. 941 44

The addition of leucovorin (LV) to 5-fluorouracil (5-FU) in advanced colorectal cancer has shown improved tumour response rates in many trials, but the optimal LV/5-FU regimen has yet to be determined. Seven studies carried out over the last 12 years to evaluate the safety and efficacy of various LV/5-FU regimens are reviewed. The initial bimonthly high-dose LV/5-FU regimen consisted of high-dose LV as a 2-h infusion followed by 5-FU as an intravenous (i.v.) bolus plus a 22-h continuous infusion (CI), repeated for two consecutive days every 2 weeks. A randomised comparison of this bimonthly high-dose LV/5-FU regimen and the NCCTG-Mayo Clinic regimen (LV [20 mg/m2/day] followed by 5-FU bolus [425 mg/m2/day] daily x 5, every 4 weeks) showed that the bimonthly high-dose LV/5-FU regimen was superior to the NCCTG-Mayo Clinic regimen in response rate and progression-free survival, but showed no difference in overall survival. In addition, toxicity was less with the bimonthly high-dose LV/5-FU regimen. These promising results led to a phase II trial of a simplified bimonthly high-dose LV/5-FU regimen consisting of LV (500 mg/m2/day) and a 48-h CI of 5-FU (1.5-2 g/m2/day) which has been administered alone or in combination. In summary, GERCOD-sponsored studies have further demonstrated that high doses of both LV and 5-FU given as a CI can improve response rates still more with acceptable toxicity. Further studies are focused on the effectiveness of combination with oxaliplatin or CPT-11 in metastatic disease and the use of high-dose LV/5-FU regimens for colorectal cancer in the adjuvant setting.
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PMID:A review of GERCOD trials of bimonthly leucovorin plus 5-fluorouracil 48-h continuous infusion in advanced colorectal cancer: evolution of a regimen. Groupe d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD). 971 64


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