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)

Thirty-eight women with epithelial ovarian cancer were treated with gemcitabine, a new antimetabolite. All had previously received platinum, and 27 had also received paclitaxel. Four patients had a partial response giving a response rate of 13% in assessable patients (n = 31) and 11% for all patients entered. Additionally, 6 patients had stable disease with >50% reduction in CA-125 for at least 3 months. Activity was seen in patients resistant to both platinum and paclitaxel. Gemcitabine was well tolerated, with uncomplicated neutropenia the main hematological toxicity. Nonhematological toxicities were generally mild and included fatigue, myalgias, and skin rash. Gemcitabine has some activity in heavily pretreated ovarian cancer patients and deserves further investigation in this malignancy.
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PMID:Activity of gemcitabine in patients with advanced ovarian cancer: responses seen following platinum and paclitaxel. 889 75

To determine the activity and toxicity of gemcitabine (2',2'-difluorodeoxycytidine), three phase II single-agent studies have been conducted in patients with non-small cell lung cancer in Japan. In an early phase II study, 17 previously treated and 47 untreated patients were treated with gemcitabine. Gemcitabine was given intravenously at a dose of 800 mg/m2 or 1,000 mg/m2 once a week for 3 weeks followed by a week of rest, repeating every 4 weeks. Although none of the patients with prior therapy responded, eight (17%) of 47 previously untreated patients showed a partial response. Toxicities of grade 3 or greater included leukopenia (12.5%), thrombocytopenia (6.3%), and anemia (15.6%). We entered 73 patients (group A) and 67 patients (group B) into two late phase II studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response (95% confidence interval, 16.5% to 37.6%) in group A. Of 67 patients, 14 (20.9%) showed a partial response (95% confidence interval, 11.9% to 32.6%) in group B. Grade 3 or greater anemia and leukopenia occurred, respectively, in 15 (20.5%) and seven (9.6%) patients in group A and in nine (13.4%) and seven (10.4%) patients in group B. Grade 3 thrombocytopenia was observed in one patient (1.4%). Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of respiratory insufficiency. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility on an outpatient basis. Further trials in combination with other active agents are warranted.
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PMID:Phase II studies of gemcitabine for non-small cell lung cancer in Japan. 919 79

A phase II study of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/gemcitabine was conducted in patients with non-small cell lung cancer (NSCLC) who had failed first-line docetaxel- or cisplatin-based chemotherapy. Eligibility criteria included histologically confirmed measurable stage IIIB or IV NSCLC and previous exposure to docetaxel- or cisplatin-based regimens, World Health Organization performance status between 0 and 2, adequate hematologic parameters, and adequate hepatic, renal, and cardiac function. Gemcitabine (900 mg/m2) was given on days 1 and 8 as a 30-minute infusion; paclitaxel (175 mg/m2) was administered on day 8 as a 3-hour infusion after appropriate premedication. Granulocyte colony-stimulating factor (150 microg/m2 subcutaneously) was given on days 9 to 15. Treatment was repeated every 3 weeks until patients experienced disease progression. From October 1995 to December 1996, 26 patients with advanced NSCLC were enrolled (three stage IIIB, 23 stage IV). All 26 patients were assessable for toxicity, and 24 were evaluable for response. Two complete (8%) and five partial (21%) responses were observed, for an overall response rate of 29% (95% confidence interval, 11% to 47%). The median duration of response was 2.5 months and the median survival was 8 months. A median of three courses per patient was administered, and the median interval between courses was 21 days. The median delivered dose was 579 mg/m2/wk gemcitabine and 54.5 mg/m2/wk paclitaxel, corresponding to a relative dose intensity of 0.97 and 0.96, respectively. Grade 3/4 neutropenia occurred in two patients (8%). Grade 3 conjunctivitis occurred in one (4%) patient and grade 2/3 neurotoxicity in eight (31%) patients. Grade 3/4 and grade 2 fatigue occurred in four (15%) and eight (31%) patients, respectively. Other toxicities were mild to moderate. These preliminary results suggest that the paclitaxel/gemcitabine combination is an active and well-tolerated salvage regimen in patients with NSCLC previously treated with docetaxel- or cisplatin-based chemotherapy. The paclitaxel/gemcitabine combination merits further evaluation as first-line treatment.
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PMID:Second-line treatment of advanced non-small cell lung cancer with paclitaxel and gemcitabine: a preliminary report on an active regimen. 933 Nov 24

Gemcitabine and paclitaxel are new cytotoxic agents that have been used both as single agents and in combination, particularly with cisplatin, in the therapy of non-small cell lung cancer (NSCLC) with promising results. The lack of overlapping toxicities and different mechanisms of action of gemcitabine and paclitaxel make the combination of these drugs appealing in the treatment of NSCLC. A number of phase I and II trials are evaluating the use of this combination of cytotoxic agents as first-line therapy and as second-line therapy in patients with advanced NSCLC. In ongoing phase II trials using a 21-day schedule, the combination of gemcitabine and paclitaxel therapy appears to be well-tolerated, with response rates ranging from 29% to 58% and hematologic toxicities that are mild to moderate in severity. Other reported toxicities included alopecia, fatigue, and flu-like symptoms, which were also mild to moderate. However, grade 2/3 neurotoxicity was also reported. In conclusion, preliminary results from these early phase II trials of gemcitabine/paclitaxel combination therapy in advanced NSCLC are encouraging.
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PMID:Gemcitabine and paclitaxel combinations in non-small cell lung cancer. 972 84

To determine the activity and toxicity of gemcitabine in non-small cell lung cancer, three phase II studies of single agent gemcitabine have been conducted between 1990 and 1994. In an early phase II study, gemcitabine was administered of 800 mg/m2 on day 1, 8, 15 every four weeks (step I), and 1,000 mg/m2 (step II). Response was observed in 3 of 13 patients with previously untreated non-small cell lung cancer, although there was no responders in the previously treated patients. Late phase II studies were performed at 20 (group A) and 24 (group B) Japanese institutions to confirm the efficacy and safety of gemcitabine administered alone in patients with non-small cell lung cancer. Seventy-three patients (group A) and 67 patients (group B) were entered into these studies. All patients had no previous chemotherapy and had measurable disease. Gemcitabine was administered at a starting dose of 1,000 mg/m2/wk for 3 weeks followed by a week of rest. The dose was escalated to 1,250 mg/m2 if severe toxicity was not seen in the previous course. Nineteen of 73 patients (26%) had a partial response in group A. Of 67 patients, 14 (20.9%) showed a partial response in group B. Grade 3 or greater toxicities included anemia (20.5%) and leukopenia (9.6%) in group A, and in 13.4% and seven 10.4% in group B, respectively. And grade 3 thrombocytopenia was observed in 1.4%. Other toxicities including hepatic toxicity, fatigue, nausea/vomiting, and fever were mild and transient. Pulmonary toxicity was observed in five patients, two of whom died of ARDS. The median durations of response were 19.6 weeks in group A and 20 weeks in group B, and median survival times were 44 and 39 weeks, respectively. In conclusion, gemcitabine is an active agent against non-small cell lung cancer with very mild toxicities. These results suggest that gemcitabine has potential utility in advanced non-small cell lung cancer on an outpatient basis. Further trials in combination with other active agents are warranted.
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PMID:[Phase II studies of gemcitabine for non-small cell lung cancer in Japan]. 1039 14

MTA has demonstrated activity in breast, lung, bladder, and gastrointestinal malignancies in early clinical trials. Gemcitabine is a cytotoxic pyrimidine antimetabolite with broad activity against solid tumors. We have demonstrated sequence-dependent in vitro cytotoxic synergy when gemcitabine exposure preceded MTA exposure in cultured human HCT-8 colon carcinoma cells. A phase I study testing this synergy in patients is in progress. To date, 14 patients with solid tumors have received 42 courses of treatment at a fixed gemcitabine dose of 1,000 mg/m2 on days 1 and 8 and escalating doses of MTA (200, 300, and 400 mg/m2) given 90 minutes after gemcitabine on day 1. Courses are repeated every 3 weeks. The median number of courses received is three (range, one to seven). National Cancer Institute Common Toxicity Criteria grade 4 hematologic toxicity lasting less than 5 days has been leukopenia and neutropenia. Mild to moderate nonhematologic toxicities include arthralgia, nausea, fatigue, fever, rash, and liver function test abnormalities. One partial response occurred in a patient with previously treated metastatic gallbladder cancer. Dose escalation continues.
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PMID:A phase I trial of MTA and gemcitabine in patients with locally advanced or metastatic cancer. 1059 62

Gemcitabine has modest activity in the treatment of advanced pancreatic cancer and is a potent radiosensitizer. We conducted a Phase I trial to determine the maximum tolerated dose of weekly gemcitabine delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreatic head and to assess the treatment-related toxic effects associated with such a regimen. Eighteen patients with pathologically proven, locally advanced adenocarcinoma of the pancreatic head were enrolled in this study. Patients received seven weekly doses of gemcitabine with 3000 cGy of external beam radiation therapy delivered during the first 2 weeks of therapy. Six patients received gemcitabine at 350 mg/m(2)/week, nine at 400 mg/m(2)/week, and three at 500 mg/m(2)/week. Grade 3-4 hematological toxicity was observed in over half the patients treated. Nonhematological toxicities were significant and included fatigue, anorexia, nausea, vomiting, and dehydration. Forty-four % of the patients required admission to the hospital for management of nausea/vomiting and dehydration. The risk of hospitalization appeared to be dose-related; all of the three patients treated at 500 mg/m(2)/week required hospital admission during treatment. Seventeen patients were evaluated for response, and eight patients (47%) had evidence of a local anticancer effect. Four of these eight patients (24%) had a partial response to therapy. The median survival for the entire group was 6 months. The 1-year survival rate for patients with an objective response to therapy was 66%. The clinical responses observed in this group of patients suggest gemcitabine is a clinically relevant radiosensitizer in patients with pancreatic adenocarcinoma. However, the toxic effects are significant, suggesting that until dose and scheduling issues are explored further, concomitant administration of gemcitabine and radiation therapy should still be considered investigational.
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PMID:Phase I trial of gemcitabine combined with radiation for the treatment of locally advanced pancreatic adenocarcinoma. 1148 98

To evaluate activity and toxicity of a non platinum-based triplet including Gemcitabine, Ifosfamide and Navelbine (GIN) in advanced NSCLC. Stage IIIB/IV NSCLC patients with WHO PS < 2 and bidimensionally measurable disease entered the study. Gemcitabine 1000 mg/sqm day 1 and 1000-800 mg/sqm day 4, Ifosfamide 3 g/sqm day 1 (with Mesna), Navelbine 25 mg/sqm day 1 and 25-20 mg/sqm day 4 were administered intravenously every 3 weeks. Objective responses (ORs) were evaluated every 2 courses: a maximum of 6 courses were administered in responding patients. According to Simon's optimal two-stage design more than 18 ORs out of 54 patients were required to establish the activity of this regimen. Fifty patients entered the study. Main characteristics of the 48 evaluated patients were: median age 63 years, ECOG performance status 0 = 65%, stage IV disease 79% and non-squamous histology 71%. The total number of courses administered was 200, median per patient 4 (range 1-6). Toxicities were evaluated according to WHO criteria: neutropenia grade 3-4 occurred in 47% of the courses; thrombocytopenia grade 3-4 in 6.6%; anaemia grade 3 in 3.5%. Twelve episodes of febrile neutropenia were reported and three patients required hospital admission. No toxic death was reported. Non-haematological toxicity, including skin rash, alopecia and fatigue, were generally. Twenty-five ORs (1 complete response and 24 partial responses) were obtained for a response rate of 52% (95% CI: 37.4-66.5%). One-year survival was 46.5%. This non-platinum-based outpatient triplet showed promising activity against NSCLC with myelosuppression, in particular neutropenia, being dose-limiting. The GIN regimen may represent a valuable alternative to standard platinum-based doublets and triplets in the treatment of advanced NSCLC and further studies with this platinum-free combination are warranted.
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PMID:Gemcitabine, Ifosfamide and Navelbine (GIN): activity and safety of a non-platinum-based triplet in advanced non-small-cell lung cancer (NSCLC). 1172 Apr 27

The aim of the present phase II study was to assess the activity and safety of gemcitabine-cisplatin combination in advanced NSCLC, and to evaluate the impact of this regimen in terms of symptom benefit and quality of life (QOL). Eighty patients with pathologically confirmed advanced (stage IIIB and IV) NSCLC were enrolled into this study. Gemcitabine was administered on days 1, 8 and 15 at a dose of 1000 mg/m(2), and cisplatin was given on day 2 at a dose of 100 mg/m(2). The cycles were repeated every 4 weeks. The impact of treatment on QOL and on tumor-related symptoms was evaluated with the validated EORTC forms (QLQ-C30 and LC-13). The regimen was relatively well tolerated. Myelosuppresion was the principal toxicity. Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 58, 65 and 30% of patients respectively. In 143 cycles (35%) the administration of gemcitabine on day 15 was omitted due to myelosuppresion. Non-hematological toxicities were generally mild. Among the 76 patients available for response evaluation, there were 5 complete responses (7%) and 26 partial responses (34%); an overall response rate of 41%. The median duration of response was 8.0 months. The median survival for all 80 patients was 11.0 months and the actuarial 1-year survival probability 45%. During therapy global QOL improved in 22% of patients and particular functional domains increased in 19-37% of patients. Dyspnea was released in 36% of patients, fatigue in 45%, chest pain in 38%, shoulder pain in 27%, cough in 44%, and hemoptysis in 75%. The mean intensity scores of the last three symptoms decreased significantly with therapy. Our study confirmed relatively high efficacy of the gemcitabine-cisplatin combination in patients with advanced NSCLC. Of particular importance was that treatment with gemcitabine-cisplatin combination in a large proportion of patients was also associated with remarkable symptomatic release and with improvement of QOL. However, the high frequency of myelotoxicity-related gemcitabine omissions on day 15 of the cycle indicates that modification of the schedule should be considered in standard care.
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PMID:A phase II study of gemcitabine plus cisplatin in patients with advanced non-small cell lung cancer: clinical outcomes and quality of life. 1175 Jul 16

Breast cancer is one of the most common cancers worldwide. Various therapies, such as hormonal therapy, chemotherapy, and biologic therapies, can increase cure rates in the early-stage setting and improve survival and quality of life in specific advanced-disease settings. For advanced disease, the optimal timing, type, and combination of drugs remain to be defined. Gemcitabine is a newer agent with a unique mode of action that involves DNA chain termination and mechanisms that result in self-potentiation. This results in a broad spectrum of activity in many types of solid tumors including breast cancer. As a single agent, gemcitabine yields response rates ranging from 14%-37% as first-line therapy for advanced breast cancer and 23%-42% as salvage therapy. However, these were small studies with large confidence intervals around all the indices of benefit including response rate, response duration, and time to disease progression. Gemcitabine was associated with higher response rates when used in combination with other agents. The side-effect profile of gemcitabine has been favorable compared to that of commonly used cytotoxic drugs, and includes myelosuppression and fatigue, with a notable absence of alopecia and gastrointestinal symptoms. Larger ongoing studies will help define the utility of gemcitabine in advanced breast cancer
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PMID:Overview: gemcitabine as single-agent therapy for advanced breast cancer. 1205 38


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