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 major purposes of this study were to determine the maximally tolerated dose (MTD), dose-limiting toxicity (DLT), toxicity profile, and antitumor activity of gemcitabine (GEM) (Gemzar) and 5-fluorouracil (5-FU) combination therapy when administered to patients with advanced solid tumors. GEM was administered intravenously over 30 minutes on days 1, 8, and 15, and 5-FU was administered as a continuous intravenous infusion from day 1 through day 15 of each 28-day treatment course. Seventeen patients (13 men and 4 women, median age 57, all previously treated with chemotherapy) were treated with 68 courses at 3 dose levels: 800/200, 1,000/200, and 1,000/300 [GEM (mg/m2/week)/ 5-FU (mg/m2/day)]. Two further patients were not fully evaluable for toxicity; one died from a probable pulmonary embolism, and one refused further treatment after developing grade II mucositis and dermatitis after her day 1 to 7 treatment. At the third dose level, 2 of 4 patients developed grade III mucositis; one also developed grade IV neutropenia with fever and grade III thrombocytopenia. Patient accrual then resumed at the second dose level. At this level, 10 patients were treated, with two developing grade III mucositis. One of these patients also developed grade IV dermatitis. No other patient developed grade III or IV side effects. Prophylactic dexamethasone was initiated after 4 of the first 7 patients (including 1 of the not fully evaluable patients) developed dermatitis-grade IV in 1 patient and grade II in the remaining 3 patients. After the steroids were initiated, 4 of the last 11 patients treated developed dermatitis, but grade 1 in all cases. One patient with metastatic gastric cancer achieved a near-complete response of his gastric mass and adrenal metastasis. Minor responses were achieved in a patient with colon carcinoma and a patient with an ethmoid sinus adenoid cystic carcinoma. The MTD and recommended dose for phase II clinical trials of GEM and 5-FU on the above schedule is 1,000 mg/m2 and 200 mg/m2 respectively, with mucositis as the DLT.
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PMID:A phase I trial of gemcitabine and infusional 5-fluorouracil (5-FU) in patients with refractory solid tumors: Louisiana Oncology Associates protocol no. 1 (LOA-1). 1068 85

In our previous phase I/II studies, both the cisplatin (Platinol), gemcitabine (Gemzar), and vinorelbine (Navelbine) (PGV), and cisplatin, gemcitabine, and paclitaxel (Taxol) (PGT) regimens produced a median survival of approximately 1 year in patients with advanced non-small-cell lung cancer (NSCLC). The present phase III study compared the median survival of patients treated with these triple-drug regimens to that of patients receiving cisplatin plus vinorelbine (PV) or cisplatin plus gemcitabine (PG). Accrual for the trial began in 1997 and by December 1998, a total of 240 patients (stage IIIB, 98; stage IV, 142) had been enrolled. An interim survival analysis was performed in April 1999. Overall, 151 patients had died. The median survival rates of patients in the PGV, PG, and PV arms were 51, 42, and 35 weeks, respectively. At the time of this analysis, the median survival of patients in the PGT arm could not be assessed; however, the 1-year projected survival rate was 58%. At multivariate Cox analysis, the estimated risk of death for patients receiving PGV compared with those receiving PV was 0.35 (95% CI, 0.16-0.77, P = .0058). Overall response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm, and 58% in the PGT arm. Severe neutropenia and vomiting were significantly more frequent in patients who received PV than in those who received PGV. The PV regimen produced a significantly shorter survival compared with the PGV combination. Since this difference in survival complied with one of the early stopping rules, accrual in the PV arm was discontinued. Enrollment in the PGV, PG, and PGT arms is ongoing.
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PMID:Interim analysis of a phase III trial. Triple- vs double-agent chemotherapy for advanced non-small-cell lung cancer. Southern Italy Cooperative Oncology Group. 1096 Sep 44

The Hellenic Cooperative Oncology Group conducted a randomized phase III trial to compare paclitaxel (Taxol) 200 mg/m2 i.v. 3-hour infusion on day 1 plus carboplatin (Paraplatin) at an area under the curve (AUC) of 6 (group A) with paclitaxel at the same dose plus gemcitabine (Gemzar) 1,000 mg/m2 on days 1 and 8 (group B) every 3 weeks for a maximum of six cycles in patients with advanced non-small-cell lung cancer. To date, 127 eligible patients have been randomized, 63 to group A and 64 to group B, and median follow-up is 4.6 months. Preliminary results suggest that both combinations are well tolerated and can be administered at full doses. Grade 3-4 neutropenia was generally mild but more prominent in group A (10%) and thrombocytopenia was insignificant in both groups. Severe neurotoxicity, hepatotoxicity, or cardiac toxicity have not been recorded in the majority of patients in either group. There was a trend toward higher response rates in favor of group B (group B vs group A, 37.5% vs 21.8%, respectively), although time-to-disease progression did not differ significantly (group B vs group A, 7.25 vs 7.1 months, respectively). Further maturation of the study is needed before definitive conclusions can be drawn.
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PMID:Interim results of a phase III trial. Paclitaxel/carboplatin vs paclitaxel/gemcitabine in advanced non-small-cell lung cancer. 1096 Sep 45

Docetaxel (Taxotere), gemcitabine (Gemzar), and irinotecan (Camptosar, CPT-11) are active single agents in a variety of solid tumors. In combination, synergism may be schedule dependent. Preclinical studies suggested synergistic interactions when docetaxel was administered 24 hours before gemcitabine or irinotecan. The objective of this phase I trial in patients with refractory solid tumors was to determine the maximum tolerated dose of docetaxel followed 24 hours later by gemcitabine and irinotecan. Two different schedules were tested: docetaxel escalated by 5 mg/m2/cohort from an initial dose of 20 mg/m2 on days 1 and 8 (schedule A) or escalated by 15 mg/m2/cohort from 45 mg/m2 on day 8 only (schedule B). In both schedules, docetaxel was given over 1 hour. Gemcitabine and irinotecan were given on days 2 and 9 (arm A) or 1 and 9 (arm B) at fixed doses of 1,000 mg/m2 over 30 minutes and 100 mg/m2 over 90 minutes, respectively. Escalation of docetaxel was planned in groups of three patients, with three additional patients added at the first indication of dose-limiting toxicity. Four dose levels in arm A and one dose level in arm B have been tested. Seventeen patients were evaluable in arm A; one died of an unrelated cause on cycle 1, and another withdrew consent before beginning treatment. Five of six patients were evaluable in arm B; one patient inadvertently received G-CSF on cycle 1. Forty-two cycles have been delivered in arm A (mean; 2.2 cycles/patient), and 25 cycles in arm B (mean, 4.2 cycles/patient); the maximum tolerated dose of docetaxel on arm A was 20 mg/m2. The dose-limiting toxicities were grade 3 diarrhea in one patient, grade 3 infection in two patients, and grade 4 neutropenia for > 4 days in one patient at the 25 mg/m2 level. The dose-limiting toxicities on arm B occurred at the first dose level and included grade 3 diarrhea in one patient, grade 4 diarrhea in one patient, and grade 4 neutropenia for 4 days in another patient. Accrual to schedule B was closed after testing the cohort 1 dose level because testing of a single deescalated docetaxel dose given on day 8 was not considered clinically relevant.
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PMID:Docetaxel followed by gemcitabine and irinotecan in solid tumors. 1122 Oct 20

Docetaxel (Taxotere) and gemcitabine (Gemzar) are active agents against breast cancer. Several phase I studies evaluated different schedules of their combination and clearly demonstrated that docetaxel and gemcitabine can be safely combined in either an every 3-week schedule or in a weekly and biweekly schedule. The toxicity profiles of these combinations were mainly grade 3 and 4 neutropenia and asthenia. Phase I studies also suggested that the docetaxel/gemcitabine combinations are active regimens in pretreated patients with advanced breast cancer. Three phase II studies of patients previously treated with anthracycline-based chemotherapy reported a mean objective response rate of 46% and a mean overall survival of 13.5 months. Two of these trials enrolled patients with anthracycline-resistant or anthracycline-refractory disease; the objective responses using docetaxel/gemcitabine combination were 36% to 55% and 54%, respectively. It is noteworthy that objective responses were also achieved with this regimen in some patients who progressed while receiving taxane-based, front-line chemotherapy. These efficacy results were obtained with a mild toxicity profile. Adverse events were of short duration and easily manageable. Further studies are needed to evaluate this combination as front-line chemotherapy as well as second-line in well-defined subgroups of patients with advanced breast cancer. Furthermore, the combination should be compared with other more standard or investigational regimens.
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PMID:Docetaxel/gemcitabine: salvage chemotherapy in anthracycline-pretreated patients with advanced breast cancer. 1125 84

Numerous trials have shown that the pharmacokinetic interferences of epirubicin (Ellence)/paclitaxel (Taxol) combinations produce less pharmacodynamic effect than doxorubicin/paclitaxel regimens. Paclitaxel is more easily combined when infused over 3 (as compared to 24) hours; the administration of optimal doses of both agents is important. Based on these findings, a phase II study was performed to evaluate the feasibility and activity of the combination of gemcitabine (Gemzar), epirubicin, and paclitaxel as first-line therapy in advanced breast cancer. Patients received gemcitabine at 1,000 mg/m2 on days 1 and 4, plus epirubicin at 90 mg/m2 on day 1, plus paclitaxel at 175 mg/m2/d on day 1 every 21 days. After six courses, patients less than 60 years old and in complete or partial remission or stable disease were treated with high-dose chemotherapy as consolidation treatment. The overall response rate was 92%, with 31% complete responses; 25 patients received high-dose chemotherapy, achieving a final overall response rate of 97%, with 47% complete responses. At a median follow-up of 25 months, median progression-free survival is 21 months. Grade 4 neutropenia was observed in 64% of patients. Other hematologic toxicities were mild. Mild to moderate peripheral neuropathy was experienced by 39% of patients; grade 2 or 3 mucositis occurred in 25% and 17% of patients, respectively. Based on these results, a multicenter trial has been started in seven Italian centers to confirm the feasibility of this regimen.
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PMID:The gemcitabine/epirubicin/paclitaxel trials in advanced breast cancer. 1125 89

Gemcitabine (Gemzar), paclitaxel (Taxol), docetaxel (Taxotere), and vinorelbine (Navelbine) are among the most active agents for the treatment of non-small-cell lung cancer and are generally more active than platinum compounds. When combined with a platinum compound, these agents have produced the best survival outcomes seen to date in non-small-cell lung cancer. More than 100 clinical trials have defined and expanded the role of gemcitabine, which has been combined with each of these agents to create novel combinations. Several new nonplatinum-based combinations compare favorably with platinum-based combinations with respect to toxicity and efficacy. Moreover, changing the schedule of gemcitabine administration from days 1, 8, 15 every 4 weeks to days 1 and 8 every 3 weeks seems to allow greater dose intensity with less severe toxicity and slightly greater efficacy. Coadministration of docetaxel, paclitaxel, or vinorelbine with gemcitabine on days 1 and 8 every 3 weeks is a promising approach. In addition to a lower incidence of severe neutropenia, docetaxel, paclitaxel, and vinorelbine protect against gemcitabine-associated thrombocytopenia.
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PMID:Gemcitabine and nonplatinum combinations in non-small-cell lung cancer. 1130 44

The survival of patients with advanced non-small cell lung cancer remains poor. Cisplatin-based chemotherapy produces a modest benefit in survival compared with that observed with best supportive care. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a novel nucleoside antimetabolite, is active and well tolerated. The combination of gemcitabine/cisplatin has shown a significant improvement in response rate and survival over cisplatin alone. Phase III trials comparing gemcitabine/cisplatin with older combinations such as cisplatin/etoposide or mitomycin/ifosfamide/cisplatin have shown a higher activity for gemcitabine/cisplatin; however, the best way to combine these drugs remains unclear. In addition, the 3-week schedule has obtained a higher dose intensity with less toxicity and similar efficacy as the 4-week schedule. The role of carboplatin in combination with new drugs is still under evaluation. Gemcitabine/carboplatin seems to be a good alternative, with the advantage of ambulatory administration and lower nonhematologic toxicity. The 4-week schedule has produced frequent grade 3/4 neutropenia and thrombocytopenia in some studies. The 3-week schedule, using gemcitabine on days 1 and 8 and carboplatin on day 1, is a convenient and well-tolerated regimen. The toxicity profile is acceptable without serious symptoms. This schedule could be considered a good option as a standard regimen. Semin Oncol 28 (suppl 10):4-9.
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PMID:Gemcitabine and carboplatin for patients with advanced non-small cell lung cancer. 1151 27

Small cell lung cancer is a chemosensitive disease; however, patients with extensive-stage disease or adverse prognostic factors are rarely cured. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a new agent with good tolerability, interacts synergistically with platinum agents. Carboplatin is as effective as cisplatin, but is less toxic. The London Lung Cancer Group is conducting a multicenter, open-label, randomized, phase III trial in patients with histologically or cytologically proven small cell lung cancer and extensive-stage, limited-stage but locally-advanced, or limited-stage disease with poor prognostic factors. Chemotherapy consists of 21-day cycles of gemcitabine 1,200 mg/m(2) intravenous (IV) on days 1 and 8, plus carboplatin area under the curve of 5 IV on day 1, or cisplatin 60 mg/m(2) IV on day 1 plus etoposide 120 mg/m(2) IV on day 1 and 100 mg orally on days 2 and 3. Thirty-nine patients have been randomized to gemcitabine/carboplatin and 38 to cisplatin/etoposide (23 and 22 completed treatment, with 96 and 84 cycles, respectively). Preliminary toxicity data indicate hematologic toxicity in 25% of cycles for gemcitabine/carboplatin and 16% for cisplatin/etoposide, although cisplatin/etoposide-treated patients experienced significant alopecia, nephrotoxicity, nausea and vomiting, and neutropenia. This London Lung Cancer Group trial of gemcitabine/carboplatin may define an active, safe, and acceptable treatment for patients with extensive-stage and poor-prognosis small cell lung cancer. Semin Oncol 28 (suppl 10):15-18.
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PMID:Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation. 1151 29

The primary goal of this phase II study was to determine the efficacy of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus 5-fluorouracil in patients with pancreatic cancer. Eligibility criteria included nonresectable locally advanced or metastatic pancreatic adenocarcinoma and measurable disease. Gemcitabine at 1,000 mg/m(2) and leucovorin at 20 mg/m(2) were administered intravenously 30 minutes before 5-fluorouracil 600 mg/m(2), weekly for 3 of every 4 weeks. Twenty nine patients were enrolled. The overall response rate was 21% (95% confidence interval: 8% to 40%), consisting of one complete response and five partial responses; 16 patients (55%) had stable disease. Median survival was 8.4 months (95% confidence interval: 2.6 to 14.2), and actuarial 1-year survival was 36%. Neutropenia (grade 3 only) was reported in 3.4% of patients, but was generally of short duration. No thrombocytopenia or evidence of cumulative myelosuppression was observed. The only significant nonhematologic events were grade 3 diarrhea and alopecia (both 3.4%). Gemcitabine plus 5-fluorouracil is active and well tolerated compared with results reported for each of these single agents. Thus, this combination justifies future comparative clinical trials. Semin Oncol 28 (suppl 10):44-49.
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PMID:Phase II study of gemcitabine, 5-fluorouracil, and leucovorin in patients with pancreatic cancer. 1151 33


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