Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CPT-11 (irinotecan) is a promising anticancer agent with a novel mechanism of action dependent on the inhibition of the DNA eukaryotic enzyme, topoisomerase I. The clinical utility of CPT-11 in advanced colorectal cancer has been documented in more than 400 patients recruited in phase II clinical trials in Europe, Japan, and United States. Among 178 eligible patients in a multicenter European study, the overall response rate to CPT-11 on a once-every-3-weeks regimen was 18%, and the median duration of response was 9.1 months. Thirty-two percent of the patients had no evidence of disease progression at 6 months. These results were similar in chemotherapy-naive and pretreated patients. These findings are consistent with the results of other studies conducted in Japan and the United States in which a weekly CPT-11 regimen was associated with response rates of 15% to 32% in chemotherapy-naive or pretreated patients. The principal adverse events of CPT-11 are neutropenia and delayed diarrhea, which in the European studies developed as grade 3 or 4 toxicity in 21% and 12% of the cycles (47% and 38% of patients), respectively. Neutropenia did not appear to be cumulative, with total recovery by day 22 in most cases. Loperamide was considered the most effective agent for controlling delayed diarrhea. Other adverse events included an early cholinergic-like syndrome (consisting of diaphoresis, early diarrhea, and abdominal cramps), nausea and vomiting, fatigue, and alopecia. In conclusion, CPT-11 has shown promising antitumor activity in the treatment of patients with advanced colorectal cancer, including those refractory to 5-fluorouracil (5-FU)-based regimens, suggesting no cross-resistance to 5-FU. CPT-11 appears to have activity similar to that of 5-FU in first-line treatment and, moreover, remains active after failure of 5-FU therapy. The specific gastrointestinal toxicity is manageable, and a better control of this type of toxicity is expected in the future. CPT-11 would therefore appear a welcome addition to the oncology armamentarium for this difficult-to-treat malignancy.
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PMID:CPT-11 in the treatment of colorectal cancer: clinical efficacy and safety profile. 863 52

A chemotherapeutic protocol for advanced thymic carcinoma has not been established as yet. We described a case of advanced and relapsed thymic carcinoma that responded remarkably to subsequent chemotherapy with CPT-11. A 61-year-old man was admitted to our hospital because of facial edema and general fatigue. Chest X-ray and CT scan showed anterior mediastinal tumor which involved large vessels and pericardium. CT guided needle biopsy yielded a diagnosis of squamous cell type of thymic carcinoma. The patient was initially treated with ADOC (ADM, CDDP, VCR, CPA) chemotherapy and had successfully controlled for six months. However, the mediastinal tumor recurred and radiotherapy and nedaplatin plus ETP therapy were not effective. Then, CPT-11 chemotherapy (80 mg/m2, 2 weeks) was performed. The patient showed a partial response after two courses of CPT-11 chemotherapy. This case suggests that CPT-11 is a useful chemotherapeutic agent for advanced thymic carcinoma.
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PMID:[A case of relapsed thymic carcinoma that responded remarkably to chemotherapy with CPT-11]. 983 15

A phase II study was conducted to assess the response rate and toxicity profile of the combination of irinotecan (CPT-11, Camptosar) and cisplatin (Platinol) administered weekly to patients with untreated advanced adeno-carcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach or gastroesophageal junction and with adequate liver, kidney, and bone marrow functions were included. Patients were treated with 65 mg/m2 of irinotecan plus 30 mg/m2 of cisplatin, both administered intravenously 1 day per week for 4 consecutive weeks, followed by a 2-week recovery period. Response rate, time to progression, survival, and toxic effects were analyzed. Thirty-six (95%) of 38 registered patients were assessable for toxicity and response. The median number of 6-week cycles per patient was 2.5 (range: 1 to 7 cycles). Four patients (11%) achieved a complete response and 17 (47%) had a partial response for an overall response rate of 58%. Median time to progression of carcinoma was 24 weeks, and median survival was 9 months (range: 1 to 23+ months). There was one treatment-related death. Major toxic effects included diarrhea, neutropenia, and fatigue. The combination of irinotecan and cisplatin is active against gastric or gastroesophageal adenocarcinoma and should undergo further study. The addition of other active drugs or radiation therapy to this regimen would be of interest.
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PMID:Irinotecan plus cisplatin in advanced gastric or gastroesophageal junction carcinoma. 1130 42

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.
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PMID:Cisplatin and irinotecan (CPT-11) as second-line treatment in patients with advanced non-small cell lung cancer. 1174 7

We conducted a phase II study to assess the response rate and toxicity profile of the irinotecan (CPT-11, Camptosar) plus cisplatin combination administered weekly to patients with at least one previous chemotherapy for advanced adenocarcinoma of the stomach or gastroesophageal junction. Patients with histologic proof of adenocarcinoma of the stomach orgastroesophageal junction with adequate liver, kidney, and bone marrow functions were treated with 50 mg/m2 of irinotecan plus 30 mg/m2 of cisplatin, both administered intravenously 1 day a week for 4 consecutive weeks, followed by a 2-week recovery period. Response rate, time to disease progression, survival, and toxic effects were analyzed. Of 32 registered patients, 29 were assessable. Nine patients (31%) achieved a partial response. Median time to disease progression was 7 weeks (range: 5-48+ weeks) and median survival time was 5 months (range: 2.5-31 months). There were no treatment-related deaths. Major toxic effects included diarrhea, neutropenia, and fatigue. Of 260 doses administered in 65 6-week courses, 46 doses were either delayed or missed. Most delayed or missed doses occurred in the third or fourth week of the cycle. We concluded that the combination of irinotecan and cisplatin is an active second-line therapy for patients with advanced gastric or gastroesophageal adenocarcinoma in whom one previous chemotherapy has failed. Modifications in doses and schedule are warranted to increase the tolerability of the regimen. Phase III trials are necessary to establish the clinical utility of irinotecan/cisplatin in these patient populations.
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PMID:Irinotecan/cisplatin in advanced, treated gastric or gastroesophageal junction carcinoma. 1210

We conducted a phase I study of irinotecan (CPT-11) and cisplatin with concurrent split-course radiotherapy in limited-disease small-cell lung cancer (LD-SCLC). This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of this therapy. Four chemotherapy cycles of CPT-11 (days 1, 8 and 15) and cisplatin (day 1) were repeated every 28 days. Radiotherapy of 2 Gy/day commenced on day 2 of each chemotherapy cycle with 20 Gy administered from the first to the third cycles (a total of 60 Gy). 17 patients were enrolled at three dose levels (CPT-11/cisplatin: 40/60, 50/60 and 60/60 mg/m(2)), and 16 were evaluable for toxicity and outcome. 2 of 4 patients at 60/60 mg/m(2) refused continuation of therapy because of general fatigue, and the relative dose intensity of CPT-11 at 50/60 mg/m(2) was approximately 50%. These levels were considered as the MTD. Tumour responses included four complete responses (CR), 11 partial responses (PR) and one no change (NC), and the overall response rate was 93.8% (95% confidence interval: (CI) 71.7-98.9%). This combined modality is tolerable, and CPT-11/cisplatin of 40/60 mg/m(2) in this modality is recommended for phase II study.
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PMID:Phase I study of irinotecan and cisplatin with concurrent split-course radiotherapy in limited-disease small-cell lung cancer. 1237 4

We retrospectively evaluated the efficacy of chemotherapy regarding symptom control, toxicity and discharge rate in 39 patients with gastric or colorectal cancer. Treatment consisted of TS-1 (n = 16), TS-1 + CPT-11 (n = 8), CDDP + CPT-11 (n = 5), paclitaxel (n = 8) and MTX + 5-FU (n = 4) for gastric cancer and 5-FU + l-leucovirin (n = 6), 5-FU + CPT-11 (n = 5), MMC + CPT-11 (n = 8) and 5-FU protracted continuous infusion (n = 5) for colorectal cancer. The rates of symptom improvement were the following: pain 60% (10/15), general fatigue 56% (5/9) and abdominal fullness 53% (8/15). 87% (34/39) of the patients were discharged from hospital and continued chemotherapy as outpatients grade 3 toxicities were the following: anemia 10.3%, nausea and/or vomiting 7.7%, diarrhea 5.1%. There was no treatment related death. The rates of outpatient based treatment duration improvement were the following: gastric cancer: 47.6%, colorectal cancer: 72%. These data suggest that these treatments for gastric and colorectal cancer are safe and improve the patients' QOL.
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PMID:[Effectiveness of chemotherapy for outpatients with gastric or colorectal cancer]. 1253 32

Peritoneal mesothelioma is a rare malignancy that is seen in patients exposed to asbestos or in young women with no known exposure to asbestos. The clinical features of the disease are similar in these two groups, and include peritoneal carcinomatosis, ascites, thrombocytemia, systemic symptoms (fever and night sweats), and hypercoagulability. There is no known curative therapy for this disease. Cisplatin has activity in 25% of patients. Mesothelial cells are known to contain high levels of carboxylesterase, a key enzyme in the activation of Irinotecan (CPT-11) to SN-38. This retrospective review of our experience in combining cisplatin 50 or 60 mg/m2 i.v. or i.p. on day 1 with CPT-11 50 or 60 mg/m2 i.v. on day 1, 8, and 15. Courses were repeated every 4 weeks x 6. If i.p. administration of cisplatin were feasible, it was the preferred route. Response to treatment was based on RECIST criteria. Fourteen men and 3 women, median age 62 years (35-76 years) and median PS 1 (0-2) were treated. Median number of courses was two for nonresponders and six for responders. The overall response rate was 24%, but 76% of patients improved on treatment. Median survival is not reached. Grade > or = 2 side effects included anemia (n = 6), neutropenia (n = 3), nausea/vomiting (n = 4), and constipation (n = 2). Grade 1 side effects were fatigue, anorexia, weight loss, alopecia, diarrhea, neuropathy, and gastric reflux. There were no grade > or = 3 hematologic toxicities. The combination of cisplatin and CPT-11 is well tolerated and has clinical benefits in patients with peritoneal mesothelioma.
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PMID:Cisplatin and irinotecan (CPT-11) for peritoneal mesothelioma. 1462 25

Colorectal cancers (CRC) express the epidermal growth factor receptor (EGF-R), a type I transmembrane receptor with tyrosine kinase activity. EGF-R signaling inhibition is a promising target for cancer therapy. ZD1839 (Iressa, AstraZeneca) and OSI-774 (Tarceva, Roche) are small molecular weight molecules with selective and reversible tyrosine kinase inhibition properties directed to EGF-R. Orally administered, these molecules induce sustained tumor stabilizations in previously treated metastatic CRC patients. The most frequent treatment-related toxicities are fatigue, diarrhea and acne-like follicular rash. The addition in the clinic of 5-FU, lOHP or CPT-11 to ZD1839 or OSI-774 does not seem to increase the own toxicity of each cytotoxic agents. Cetuximab (Erbitux, Merck) is an intravenously administered humanized monoclonal antibody which bind with high affinity with the extracellular domain of the EGF-R. The most frequent treatment-related toxicities are diarrhea, fatigue, nausea and cutaneous toxicity (allergic or acne-like follicular rashes, folliculitis). Most, if not all of these adverse events are mild. Partial responses were observed with cetuximab either alone (RR: 10%) or in combination with CPT-11 (RR: 22%) in patients with CPT-11 refractory advanced CRC which expressed EGF-R. The combination of cetuximab to folinic acid, 5-FU and CPT-11 seems tolerable at the cost of a slight increase of severe diarrhea and neutropenia. Finally, the promising activity of these EGF-R inhibitors has to be confirmed throughout randomized studies.
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PMID:[Inhibitors of epidermal growth factor receptor and colorectal cancer]. 1476 44

TS-1/CPT-11 combination therapy was carried out in a case of advanced gastric cancer with liver and lymph node metastases and obstructive jaundice after percutaneous transhepatic cholangio drainage (PTCD). Regression of the primary carcinoma and reduction in size of metastases were observed. Grade 1 fatigue and grade 2 neutropenia were noted as adverse reactions to the treatment. TS-1/CPT-11 combination therapy was useful in this case of advanced gastric cancer with liver and lymph node metastases.
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PMID:[A case of advanced gastric cancer with obstructive jaundice that responded to TS-1/CPT-11 combination therapy after percutaneous transhepatic cholangio drainage]. 1622 50


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