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 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

This multicenter study enrolled 73 patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). The study design was based on the hypothesis that the non-overlapping toxicities of a 3-drug combination of irinotecan (Camptosar, CPT-11), carboplatin (Paraplatin), and paclitaxel (Taxol) would allow them to be dosed at recommended or standard doses, respectively. Of the 32 patients in phase I portion of the trial, six received irinotecan 40 mg/m2 plus carboplatin at an area-under-curve (AUC) of 6 and paclitaxel 225 mg/m2 on an every-3-week schedule (regimen A). Due to the unexpectedly severe toxicity associated with this regimen, the carboplatin and paclitaxel doses were reduced, while the irinotecan doses were escalated from 40 to 80 to 125 mg and reduced to 100 mg/m2 (regimen B). In the phase II portion of the trial, irinotecan was dosed at 100 mg/m2 because 3 of 8 patients who received the 125 mg/m2 dose in phase I experienced first-course grade 3/4 toxicities. However, the toxicity of regimen B proved unacceptably severe in phase II; 13 of the 40 patients (35%) experienced grade 3/4 neutropenia and 30% suffered febrile or septic neutropenia. The unconfirmed objective response rate in phase I was 64.5%; median time to progression and median survival were 7.1 months and 11.6 months, respectively, and 1-year survival was 46.9%. The unconfirmed objective response rate in phase II was 60.6%, including one complete response (CR) and 19 partial responses (PRs); one CR and 16 PRs were subsequently confirmed. The efficacy and toxicity of this triple combination strongly suggest significant pharmacokinetic and/or pharmacodynamic interactions, warranting continued clinical investigation.
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PMID:Phase I/II trial of irinotecan, carboplatin, and paclitaxel in advanced or metastatic NSCLC. 1098 Dec 88

We conducted a dose-finding study for combination therapy of paclitaxel (Taxol; TXL) and carboplatin (Paraplatin; CBDCA). TXL is a novel plant-derived anticancer agent that is a diterpene derivative possessing the taxane ring. The subjects were patients with ovarian carcinoma, who were evaluated by a modified Fibonacci method. The dosage of TXL was 150 to 180 mg/m2. CBDCA was administered by dose escalation from AUC = 4 to 7. The administration schedule was as follows. Pre-medication was administered before TXL was given. TXL was then administered by intravenous infusion over 3 hours, followed by CBDCA. The dose of CBDCA was determined using the Calvert formula: [AUCX (GFR + 25)]. GFR was calculated with the Jelliffe equation. The non-hematological toxicities observed in 15 eligible cases were mainly grade 1, with no grade 3 or above, and no increase in severity was observed with stepping up. The hematological toxicities were grade 3 leukopenia in 5 of 15 cases, neutropenia in 5 cases and thrombocytopenia in 0 cases. No grade 4 toxicity was observed. The lowest counts of leukocytes and neutrophils were reached after 10.8 and 11.7 days, respectively. The toxicities were reversible in most cases with subsequent recovery. The above findings indicate that the recommended dosages for TJ therapy for Japanese ovarian cancer patients should be TXL 180 mg/m2 and CBDCA at a target of AUC = 6.
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PMID:[Dose finding study of paclitaxel and carboplatin for ovarian cancer (JKTB)]. 1132 83

Docetaxel (Taxotere) has extended the armamentarium of agents with significant activity in the treatment of ovarian cancer. As a single agent in advanced ovarian cancer patients previously treated with a platinum agent, docetaxel at 100 mg/m2 every 3 weeks yields a 30% overall response rate and a 6-month duration of response. In vitro data demonstrate a lack of complete cross-resistance between docetaxel and paclitaxel. As a result, antitumor activity has also been demonstrated in patients refractory to a paclitaxel-containing regimen. In both platinum- and paclitaxel-pretreated patients, the highest response rates were obtained in patients with the longest interval of time since receipt of prior chemotherapy. Docetaxel has been successfully combined with the platinum salts for the first-line treatment of ovarian cancer patients. In combination with cisplatin, response rates of 69% were reported. In an effort to minimize hematologic toxicities and asthenia associated with the cisplatin/docetaxel combination, investigators have substituted carboplatin (Paraplatin) for cisplatin. Several phase II studies and the Scottish Randomized Trial in Ovarian Cancer (SCOTROC), a large phase III randomized trial, of the docetaxel/ carboplatin combination have been completed. The most frequent toxicity noted is neutropenia, which is generally of brief duration, predictable, and manageable. The docetaxel/carboplatin combination has a notably low rate of neurotoxicity. Therefore, the SCOTROC comparative trial, demonstrating equivalent overall response rates and progression-free survival rates, suggests that the docetaxel/carboplatin combination may represent a new alternative to paclitaxel/carboplatin as first-line chemotherapy for advanced ovarian cancer.
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PMID:Docetaxel in the treatment of ovarian cancer. 1210

Despite the high objective response rate of advanced ovarian cancer to combination platinum/taxane-based chemotherapy, the majority of patients ultimately experience disease progression. Thus, there is a need to find new management strategies that can improve upon the results of existing therapies. We are currently conducting a phase II trial to explore the toxicity and potential efficacy of a three-drug program, which adds irinotecan (CPT-11, Camptosar) at 100 mg/m2 to carboplatin (Paraplatin) at an area under the concentration-time curve of 5 and paclitaxel at 150 mg/m2 over 3 hours. Treatment was initially given on an every-3-week schedule, but was subsequently changed to an every-4-week schedule due to excessive bone marrow toxicity. The study remains in progress, with 26 patients currently evaluable for toxicity, which has included grade 4 neutropenia (42% incidence), grade 4 thrombocytopenia (12%), and grade 3 emesis (12%), with one patient each experiencing grade 3 diarrhea, hepatic dysfunction, and insomnia. Data regarding response rates are immature. Our preliminary analysis reveals that the combination of carboplatin/paclitaxel/irinotecan can be administered to women with advanced ovarian cancer with significant, but overall acceptable, toxicity. Randomized trials will be required to define a possible role for this three-drug combination chemotherapy regimen in the standard management of advanced ovarian cancer.
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PMID:Toxicity associated with carboplatin/paclitaxel/Irinotecan use in advanced ovarian cancer: preliminary analysis. 1280 Jun 4

A novel schema of intrapatient dose escalation was applied to determine a population-based maximum tolerated dose (pMTD) for irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in a phase I trial. A total of 74 patients with advanced solid tumors were enrolled with the following characteristics: men/women, 46/28; median age, 61 years; 51 patients with and 23 patients without prior chemotherapy; performance status of 0-1 (93%) and 2 (7%). Patients were started at dose level 1 with irinotecan at 200 mg/m2, and carboplatin at an area under the concentration-time curve (AUC) of 5 mg/mL x min, administered every 21 days. Depending on degree of toxicity observed, the dose for each patient in each subsequent cycle was determined according to a predetermined schema of dose levels. Individual maximum tolerated dose (iMTD) was determined for each patient. The pMTD was defined as the highest dose level for which the incidence of dose-limiting toxicity occurred in less than 33% of the patient population. The most common dose-limiting toxicity included neutropenia (58%), thrombocytopenia (15%), diarrhea (8%), and nausea/emesis (7%). The iMTD ranged from dose level-3 (irinotecan at 100 mg/m2 and carboplatin at an AUC of 4) to dose level 5 (irinotecan at 350 mg/m2 and carboplatin at AUC 6). The pMTD was determined to be dose level-1 and 1 for previously chemotherapy-treated and--untreated patients, respectively. Fifty-nine patients were assessable for response. Of note, a response rate of 40% was observed in 15 patients with relapsed small-cell lung cancer previously treated with platinum-based therapy. We recommend dose level 1 of irinotecan (200 mg/m2) and carboplatin (AUC 5) for chemotherapynaive patients, and dose level-1 of irinotecan (150 mg/m2) and carboplatin (AUC 5) for chemotherapy-treated patients in phase II trials.
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PMID:Population-based maximum tolerated dose of irinotecan and carboplatin. 1288 68

The outcome of patients with metastatic lung cancer is poor, with a 1-year survival rate of approximately 35%. We are evaluating the combination of irinotecan (CPT-11, Camptosar) and carboplatin (Paraplatin) in patients with stage IIIB and IV non-small-cell lung cancer. Eligible patients include those with histologic or cytologic diagnosis of non-small-cell lung cancer; no previous chemotherapy for metastatic lung cancer; and Eastern Cooperative Oncology Group performance status 0 or 1. The first five patients received irinotecan at 250 mg/m2 over 90 minutes followed by carboplatin at an area under the concentration-time curve (AUC) of 5 over 1 hour. Subsequently, the dose of irinotecan was reduced to 200 mg/m2 in view of febrile neutropenia in one of five patients. Chemotherapy cycles are repeated every 21 days. Patients are reevaluated every two cycles. Of a planned 37 patients, 14 have been enrolled and 9 are evaluable for toxicity and response at the time of this report. Thirty-two cycles have been administered, with seven 1-week delays and two dose reductions. To date there have been two partial responses and five patients with stable disease; two patients developed progressive disease on therapy. One patient had neutropenic fever; other toxicities included mild pancreatitis (n = 1) and diverticulitis (n = 1). The regimen of irinotecan and carboplatin administered once every 3 weeks demonstrates early evidence of activity, and is tolerable and convenient. The main toxicity is hematologic. This study is ongoing and actively accruing patients.
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PMID:Irinotecan and carboplatin in metastatic or recurrent non-small-cell lung cancer. 1288 71

This Phase II trial was designed to evaluate the overall objective response rate, complete response rate, efficacy, and safety of weekly paclitaxel (Taxol) and carboplatin (Paraplatin) in the treatment of advanced urothelial carcinoma. Thirty-three patients with measurable, unresectable, stage III-IV carcinoma of the urothelium were enrolled. Paclitaxel (135 mg/m2) and carboplatin (AUC=2) were given by intravenous (IV) infusion weekly x 6 followed by two weeks rest. Patients were premedicated with oral dexamethasone, diphenhydramine, and cimetadine (or equivalent). Patient characteristics included an Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 (36%), one (36%), two (28%); median age 70 years (37-83); 29 (88%) male, four (12%) female; 16 (48%) patients had prior chemotherapy [eight postoperative (adjuvant), five neoadjuvant, three for metastatic disease] and eight (24%) had prior radiation therapy. Eight patients (24%) achieved objective responses, three complete responses (CR) and five partial responses (PR); one patient was not evaluable (patient died prior to first dose). The median duration of response was 13 months (range, 2-29). Nine patients (27%) had stable disease (SD) and 15 patients (45%) had progressive disease (PD). Median time to progression was 3.6 months (range, < 1-29) and median survival was 10.3 months (range, < 1-33). Grade 3 and 4 toxicities included: asthenia (46%), neutropenia (36%), leukopenia (15%), thromboembolism (12%), diarrhea (9%), nausea and vomiting (9%), hyperglycemia (7%), and neuropathy (6%). Two patients died of sepsis, one death was treatment-related. Weekly paclitaxel plus carboplatin shows promising activity; however in the current study, efficacy may have been limited by the toxicities associated with this dose-intensive regimen in an elderly, pretreated patient population with poor performance status. This regimen warrants further study, perhaps as a three out of four week regimen or at reduced doses.
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PMID:A phase II evaluation of weekly paclitaxel plus carboplatin in advanced urothelial cancer. 1549 58

The 1-year survival for patients with metastatic non-small-cell lung cancer is only around 35%. We are evaluating the combination of irinotecan (Camptosar) and carboplatin (Paraplatin) in patients with stage IIIB and IV non-small-cell lung cancer. The first five patients received irinotecan, 250 mg/m2 over 90 minutes followed by carboplatin at an area under the concentration-time curve of 5 over 1 hour1 The dose of irinotecan was subsequently reduced to 200 mg/m2 in view of febrile neutropenia in one of five patients. Chemotherapy cycles are repeated every 21 days. Patients are reevaluated every two cycles. Of a planned 42 patients, 37 have been enrolled so far. Of the 37 enrolled patients, 25 received at least two cycles, 20 received at least four cycles, and 12 received all six planned cycles. Grade 4 neutropenia (absolute neutrophil count <500) occurred in 10 patients and 19 treatment cycles. Two of these patients also had grade 4 diarrhea. Thirty-six cycles (30%) were delayed for neutropenia, six of which occurred among the first five patients who received irinotecan at 250 mg/m2. Best response to therapy included 7 partial responses (23%), 11 stable disease (37%), with 12 patients having progressive disease (40%). The regimen of irinotecan and carboplatin administered once every 3 weeks is tolerable and convenient, with early evidence of activity. The main toxicity is hematologic. This study is ongoing and actively accruing patients.
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PMID:Irinotecan and carboplatin in metastatic or recurrent NSCLC: an update. 1568 28

The purpose was to conduct an integrated analysis of the cumulative hematologic toxicity of topotecan in patients with relapsed ovarian cancer and small cell lung cancer (SCLC). Data were pooled from eight phase II and phase III clinical studies performed in patients with relapsed stage III/IV ovarian cancer or extensive SCLC treated with topotecan at a dose of 1.5 mg/m(2) per day on days 1-5 of a 21-day course. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. A total of 4,124 courses of therapy was administered to the 879 patients in the pooled population. Grade 4 neutropenia was experienced by 78% of patients. The lowest nadirs for neutrophils and platelets generally occurred after the first course of therapy, followed by improvement or stabilization in subsequent courses. Neutropenia was noncumulative. During the first course, significant risk factors were identified: renal impairment and advanced age (grade 3/4 thrombocytopenia and grade 4 neutropenia) and prior radiotherapy; performance status score > or =2; SCLC; and exposure to both cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb) (grade 3/4 thrombocytopenia only). The most frequent interventions for hematologic toxicities were RBC transfusions, treatment delays, G-CSF support, and dose reductions. Analysis of neutrophil and platelet nadirs and dosing for each course of therapy showed no apparent evidence of cumulative neutropenia or thrombocytopenia. The risk of grade 3 or 4 anemia was higher during the first four courses of therapy and may need to be more aggressively managed with erythropoietin therapy.
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PMID:Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and small cell lung cancer: an integrated analysis. 1672 Aug 54


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