Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to evaluate the efficacy and tolerability of single-agent gemcitabine in untreated elderly patients with stage IIIb/IV non-small-cell lung cancer (NSCLC). Since April 1997, 46 consecutive patients have been enrolled in this multicenter study. Gemcitabine 1,000 mg/m2 was administered as a 30-minute intravenous infusion on days 1, 8, and 15 every 28 days. Primary patient characteristics were: male/female 38/8; median age 73 years (range: 70-82 years); median Karnofsky performance status (PS) 90 (range: 70-100); stage IIIb 61% and stage IV 39%; histotype: epidermoid 48%, adenocarcinoma 43%, and large cell carcinoma 9%. No complete response was observed, but 10 (21.7%) patients achieved partial response (PR) (95% confidence limits: 11-36%), 27 (58.7%) had stable disease (SD), and 7 (15%) progressed early (at the first evaluation). The median duration of PR and SD was 8 months (range: 4-23+ months) and 4 months (range: 2-9 months), respectively. Subjective response evaluating PS and symptoms such as dyspnea, pain, and cough was evaluated in 40 patients; 11 (27.5%) improved, 15 (37.5%) remained stable, and 14 (35%) worsened. The median time to progression was 4 months, the median survival was 9 months, and 1-year survival was 44%. After a median follow-up of 10.5 months, 14 patients are still alive. There were no grade 4 toxicities. Grade 3 neutropenia and thrombocytopenia occurred in 19% and 2% of patients, respectively. Nonhematologic toxicities were mild. Grade I/II side effects of nausea/vomiting, transient fever, increase of hepatic transaminases, transient peripheral edema at lower extremity (not related to cardiac or renal disease or phlebothrombosis) were reported. This phase II study confirms the activity and favorable toxicity profile of single-agent gemcitabine in the treatment of elderly patients with advanced NSCLC.
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PMID:Prospective phase II study of single-agent gemcitabine in untreated elderly patients with stage IIIB/IV non-small-cell lung cancer. 1180 66

Alternating chemoradiotherapy was shown by our institution to be superior to standard radiation in patients with nonsurgical squamous cell carcinoma of the head and neck (SCC-HN). Gemcitabine has shown in vitro and in vivo radiosensitizing properties, synergistic activity with cisplatin, and cytotoxic activity against SCC-HN. Thus, the authors tested the feasibility and antitumoral activity of a modified alternating chemoradiotherapy program that includes gemcitabine. Fourteen patients with stage IV (nine patients) or relapsed after surgery (five patients) unresectable SCC-HN were enrolled. None had previously received chemotherapy or radiotherapy. The treatment plan consisted of cisplatin, 20 mg/m2/day, days 1 to 5, weeks 1 and 5, and gemcitabine 800 mg/m2, day 5, weeks 1, 2, 3, and 5, 6, 7. Radiation was administered during weeks 2, 3, and 4 and 6, 7, and 8 with conventional fractionation up to 60 Gy. At the end of the combined therapy, patients had to receive two additional courses of cisplatin, 20 mg/m2/day, and fluorouracil, 200 mg/m2/day, for 5 days every 21 days. All the patients are evaluable for toxicity and 11 for response. Main grade III-IV toxicities and frequencies were: neutropenia (79%), neutropenia with fever (50%), thrombocytopenia (57%), anemia (35%), mucositis (100%), and cutaneous toxicity (14%). Ten patients (71%) had a weight loss greater than 10%. All but two patients needed hospitalization and tube feeding or parenteral nutrition. The median relative dose intensity of gemcitabine actually delivered was 83%. Two patients died 1 month after the end of treatment before the final evaluation. One patient died of sepsis during the additional cisplatin and fluorouracil courses before response assessment. Ten patients reached a complete response (intention to treat: 71%), and 1 patient had a partial response (9%). At a median follow-up of 34 months, the actuarial 3-year progression-free survival and overall survival are 41% and 63%, respectively. The estimated 3-year locoregional control is 70%. Considering the expected poor prognosis of the enrolled patients, this combined regimen showed an impressive antitumoral activity, but the severity of acute local and hematologic toxicity correlated makes the exportation of this regimen unproposable. However, the activity observed warrants the exploration of different, less toxic, chemo-radiotherapy programs including gemcitabine.
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PMID:Gemcitabine, cisplatin, and radiation in advanced, unresectable squamous cell carcinoma of the head and neck: a feasibility study. 1180 67

Most cytotoxic drugs have gross effects on the immune system, such as neutropenia and lymphopenia. However, their effects on tumor-specific immune responses are unknown. Gemcitabine is a nucleoside analogue that is frequently used to treat non-small cell lung cancer. It is also active in other malignancies, either alone or in combination with cisplatin. Here, we investigate its effects on antigen-specific antitumor immunity using a murine tumor cell line transfected to express influenza virus hemagglutinin (HA). CD4(+), CD8(+), and B220(+) lymphocyte numbers all decreased during chemotherapy (120 microg/g, i.p., every third day for five doses), but B cells were selectively depleted. Gemcitabine induced a profound suppression of the IgG antibody response to HA, and this was unrelated to tumor size. In contrast, in vitro T-lymphocyte recall responses to the class I- and class II-restricted dominant peptide epitopes of HA were enhanced in tumor-bearing, gemcitabine-treated mice. We found that gemcitabine was >2-fold more potent in its ability to inhibit B-lymphocyte proliferation compared with T-lymphocyte proliferation. Thus, gemcitabine does not appear to be detrimental to specific antitumor cellular immunity and may be useful in combination chemo-immunotherapy protocols. In contrast, vaccination protocols requiring a humoral immune response for maximal efficacy may be compromised in patients treated with gemcitabine.
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PMID:Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy. 1195 96

Gemcitabine is a cytosine arabinoside (Ara-C) analog with activity in many human tumor systems. We evaluated the drug's activity in resistant or relapsing multiple myeloma. Gemcitabine 1000 mg/m2 was administered as a 30 minute infusion on days 1, 8, and 15 of a 28-day cycle. No dose escalations were permitted and dose reductions were scheduled for hematologic toxicity. Twenty-nine eligible patients were entered into Southwest Oncology Group (SWOG)-9803. One patient received no treatment and 5 patients had inadequate response assessments. The major toxicity was hematologic with grade 3/4 neutropenia in 9 and grade 3/4 thrombocytopenia in 15 patients. No responses were seen. Stable disease was confirmed in sixteen patients (57%). Median survival was eight months. Gemcitabine as utilized in this trial has shown little activity and is not to be strongly considered for future multiple myeloma trials.
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PMID:The evaluation of gemcitabine in resistant or relapsing multiple myeloma, phase II: a Southwest Oncology Group study. 1200 87

A feasibility study was performed to assess the toxicity and efficacy of a combination of gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer (LAPC). 24 patients (15 females and 9 males) with measurable LAPC were included; the median age of the patients was 63 years (range 39-74 years). The performance status ranged from 0 to 2. Gemcitabine was administered at a dose of 300 mg/m(2), concurrent with radiotherapy, three fractions of 8 Gy, on days 1, 8 and 15. When compliance allowed, gemcitabine alone was continued thereafter, at 1000 mg/m(2), weekly times 3, every 4 weeks, depending on the response and toxicity. All patients were evaluable for toxicity and response. The objective response rate was 29.2% (1 complete remission+6 partial remissions); 12 patients had stable disease. However, 2 of the radiological partial remissions were shown to be complete remissions by pathology assessment. Median duration of response was 3 months (range 1-35+months). Median time to progression was 7 months (range 2-37+months). Median survival was 10 months (range 3-37+months). Dose reduction or omission of gemcitabine was necessary in 10 patients. Non-haematological toxicity consisted of 87.5% nausea and vomiting grade I-II, diarrhoea 54%, ulceration in stomach and duodenum 37.5% (20.8% ulceration with bleeding); 1 patient developed a fistula between the duodenum and aorta, 5 months after treatment. Anaemia grade III-IV was observed in 8.3% of the patients. Neutropenia grade III-IV was observed in 8.3%, thrombocytopenia grades III-IV in 16.7%. In 1 patient who underwent resection postchemoradiation, no viable tumour cells were found. In addition, in the patient who suddenly died of a fistula between the duodenum and aorta, no viable tumour cells were detectable at autopsy. Although the toxicity of this treatment was occasionally severe, the response and survival are encouraging and warrant further studies of this combination.
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PMID:Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer. 1204 8

This study investigated the maximum-tolerated dose of gemcitabine based on the frequency of dose-limiting toxicities of weekly gemcitabine treatment with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Fifteen patients with locally advanced pancreatic cancer that was histologically confirmed as adenocarcinoma were enrolled in this phase I trial of weekly gemcitabine (150-350 mg x m(-2)) with concurrent radiotherapy (50.4 Gy in 28 fractions). Gemcitabine was administered weekly as an intravenous 30-min infusion before radiotherapy for 6 weeks. Three of six patients at the dose of 350 mg x m(-2) of gemicitabine demonstrated dose-limiting toxicities involving neutropenia/ leukocytopenia and elevated transaminase, while nine patients at doses of 150 mg x m(-2) and 250 mg x m(-2) did not demonstrate any sign of dose-limiting toxicity. Of all 15 enrolled patients, six patients (40.0%) showed a partial response. More than 50% reduction of serum carbohydrate antigen 19-9 level was observed in 13 (92.9%) of 14 patients who had pretreatment carbohydrate antigen 19-9 levels of 100 U x ml(-1) or greater. The maximum-tolerated dose of weekly gemcitabine with concurrent radiotherapy was 250 mg x m(-2), and this regimen may have substantial antitumour activity for patients with locally advanced pancreatic cancer. A phase II trial of weekly gemcitabine at the dose of 250 mg x m(-2) with concurrent radiation in patients with locally advanced pancreatic cancer is now underway.
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PMID:A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer. 1208 3

Early clinical studies combining irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) have yielded encouraging results. Gemcitabine administered via a twice-weekly schedule results in an enhanced radiation-sensitizing effect. This multi-institution phase II trial of induction irinotecan/gemcitabine followed by twice-weekly gemcitabine and upper abdominal radiation has been initiated to determine the activity of this regimen in patients with unresectable pancreatic cancer. Patients received two cycles of induction irinotecan (100 mg/ m2 IV) and gemcitabine (1,000 mg/m2 IV) on days 1 and 8 of each 3-week cycle. Following the induction therapy, patients without disease progression received twice-weekly gemcitabine at 40 mg/m2 and radiation. Nine patients have been enrolled in the study to date. Median patient age was 71 years (range: 65-85 years). The major toxicity observed thus far was grade 3/4 neutropenia. Grade 3/4 nonhematologic toxicity was rarely observed and included dehydration (12%) and diarrhea (12%), which were likely related to the irinotecan. No treatment-related deaths have occurred. These preliminary data suggest that this regimen is well tolerated. Although the data are limited, tumor progression during the induction chemotherapy has not been observed thus far (radiographically or biochemically [CA-19-9]).
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PMID:Irinotecan/gemcitabine followed by twice-weekly gemcitabine/radiation in locally advanced pancreatic cancer. 1210 2

The aim of the study was to assess the efficacy of a combination of gemcitabine and cisplatin in advanced non-small cell lung cancer. Twenty-five patients were included (13--IIIB, and 12--IV stage). Gemcitabine--1000 mg/m2 was given intravenously on days 1, 8, and 15, and cisplatin--100 mg/m2 on day 2. In 13 patients partial remission was obtained, in 8--stabilisation, and in 4--progression. Median survival was 12 months (range: 1.5-32 months). Mean time to progression was 6 months. Toxicity was tolerable and included mainly thrombocytopenia, neutropenia and anemia. In 11 patients pain relief was obtained. Furthermore cough, dyspnoea and hemoptysis disappeared in a proportion of patients. These results indicate the efficacy of the combination of gemcitabine and cisplatin regimen in advanced non-small cell lung cancer, and its acceptable toxicity.
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PMID:[Chemotherapy of advanced non-small cell lung cancer with the combination of gemcitabine and cisplatin]. 1214 75

Gemcitabine is a pyrimidine nucleoside analog with antitumor activity against solid tumor malignancies and leukemia. We evaluated its activity as a single agent and combining it with cisplatin in relapsed-refractory multiple myeloma (MM). Sixteen patients with advanced MM received intravenous gemcitabine 1250 mg/mq (days 1, 8 and 15) as a single agent for a total of 3 monthly courses. The responders received another three courses, and the non-responders received three courses of gemcitabine 1000 mg/mq (days 1, 8 and 15) plus cisplatin 80 mg/mq (day 1). No grade 4 hematological toxicity was seen after gemcitabine treatment, whereas > or = 3 grade neutropenia and thrombocytopenia were seen in 21 and 13% of the gemcitabine-cisplatin infusions, respectively. Non-hematological toxicity was negligible for both the regimens. After three courses of gemcitabine as a single agent, th e response rate was 31% (1 complete response, 1 partial response and 3 minimal response). Eight patients (50%) achieved stable disease and 3 (19%) had disease progression. Ten patients received gemcitabine-cisplatin and were evaluable for the response. Two patients progressed, four maintained stable disease whereas four patients, unresponsive to gemcitabine, obtained a response (3 partial response and 1 minimal response). With a median follow-up of 13 months (range 8-17.5), 7 patients (44%) died, 5 (31%) had disease progression, 1 (6%) relapsed, 1 was still in partial response (+11 months) and 2 (13%) had a stable disease. Median time to treatment failure (TTF) was 8 months (CI95%: 7.6-8.4) and median overall survival (OS) was 16 months (CI95%: 10-22). These results showed that gemcitabine and gemcitabine-cisplatin were feasible regimens and well tolerated in advanced relapsed-refractory MM. The response rates, the TTF and OS were similar to other salvage chemotherapy regimens; nevertheless, the quality of response was modest particularly after gemcitabine alone. Better results might be obtained combining gemcitabine with other chemotherapy compounds or with biologically based therapies.
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PMID:Gemcitabine alone or combined with cisplatin in relapsed or refractory multiple myeloma. 1215 96

Platinum-based combination chemotherapy has become the standard treatment for good performance patients with stage IIIb and IV non-small cell lung cancer (NSCLC). However, newer agents such as gemcitabine and paclitaxel appear to have superior single agent activity and are more easily tolerated in comparison to the older platinum compounds. Therefore, we conducted this phase II study to evaluate the activity and toxicity of the combination paclitaxel and gemcitabine in advanced NSCLC. Gemcitabine was given at 1,000 mg/m(2) intravenously over 30 min followed by paclitaxel at 110 mg/m(2) intravenously over 1 h on days 1, 8 and 15 every 28 days for a maximum of 6 cycles. Between April 1998 and June 1999, 40 of 42 patients entered were eligible and received chemotherapy. Data was available on 39 patients. Toxicities included Grade 3/4 neutropenia in 43% of patients, while thrombocytopenia (13%) and anemia (7%) were less frequent. Five (12.5%) patients developed neutropenic fever. Four (10%) patients developed bilateral interstitial shadows with hypoxia suggestive of a drug-induced pneumonitis. There were 4 treatment-related deaths (1 from pneumonitis, 3 from neutropenic complications). Five patients were not evaluable due to early death. Therefore, 34 patients were evaluable with 12 (35.3%) achieving a partial remission and 1 achieving a complete remission for an overall response rate of 38.2% (32.5% on an intention-to-treat basis). The median progression free survival was 107 days (range, 14-391), median survival was 148 days (range, 12-495) and 1-year survival was 26%. In conclusion, weekly gemcitabine with paclitaxel in patients with advanced NSCLC is an active regimen; however, toxicity and poor survival precludes the use of this regimen as an experimental arm on a future phase III study.
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PMID:A phase II study of weekly gemcitabine and paclitaxel in patients with previously untreated stage IIIb and IV non-small cell lung cancer. 1236 96


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