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)

Thirty-four women with metastatic breast cancer were treated at the National Cancer Institute of the National Institutes of Health, with a regimen of leucovorin (L), 500 mg/m2 i.v. over 30 min, followed in 1 h by 5-fluorouracil (5-FU), 375 mg/m2 i.v. bolus on days 1-5, and carboplatin (CBDCA), 50-100 mg/m2 i.v. bolus on days 2-4, every 28 days. All patients had received previous combination chemotherapy with at least one regimen (29 patients with 5-FU-containing regimens). CBDCA, 100 mg/m2 on days 2-4, resulted in grade 4 neutropenia in 10 out of 11 patients associated with sepsis in all 10 patients. CBDCA, 75 mg/m2 (seven patients) and 50 mg/m2 (15 patients), resulted in grade 4 neutropenia in six and eight patients, and neutropenic sepsis in five and two cases, respectively. Grade 4 thrombocytopenia occurred in 10, five and two patients receiving 100, 75 and 50 mg/m2 of CBDCA, respectively. Other toxicities included grade 3/4 mucositis in 18 patients and grade 3/4 diarrhea in 10 patients. Twenty nine patients were evaluable for response, with one pathologic complete response (3%), two partial responses (6%), 18 stable disease (53%) and eight (24%) progressive disease. Sites of response included bone, viscera and soft tissue. The median time from entry on study to progression, for responders, was 15 months. When platinum-DNA adduct formation in peripheral white blood cells was analyzed in 27 patients at 24 h after drug administration, a significant correlation between adduct level and CBDCA cumulative dose was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapy of patients with metastatic breast cancer with 5-fluorouracil, leucovorin and carboplatin. 145 Apr 39

Thirty-five patients were entered in a Phase I trial of an admixture infusion of etoposide (VP-16) and carboplatin (CBDCA) administered continuously for 5 or 7 days. Because of the compatibility and solubility of the two agents, the treatment program could be administered on an outpatient basis. The dose rate of VP-16 was fixed at 30 mg/m2/day (total dose 150 mg/m2 for 5 days or 210 mg/m2 for seven days) for each cycle. Carboplatin was evaluated at three dose rates: 50, 60, and 75 mg/m2/day on the 5-day infusion and 40, 50, and 60 mg/m2/day on the 7-day infusion with cycles repeated at 28 to 42 days. The dose limiting toxicity was hematologic and followed a pattern typical for carboplatin, that is, delayed neutropenia and/or thrombocytopenia with a protracted leukocyte recovery. Renal toxicity was observed in three patients. The optimum total dose for the infusional carboplatin component was 300 mg/m2 (5-day) and 420 mg/m2 (7-day). The total etoposide dose was 150 mg/M2 and 210 mg/M2, which did not appear to contribute to the hematologic toxicity. Delivery of the admixture of VP-16 and CBDCA was feasible, although cumbersome, as a result of the portable delivery system. Extending the duration of infusion increases the total cumulative dose of carboplatin and etoposide that can be administered without increasing adverse effects.
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PMID:Etoposide plus carboplatin admixture. Phase I study of five- or seven-day continuous infusion. 151 27

In all, 18 patients with histologically proven advanced cancer received 400 mg/m2 carboplatin (CBDCA) plus 800 mg/m2 cyclophosphamide (level 1), and 14 others received 550 mg/m2 CBDCA plus 1100 mg/m2 cyclophosphamide (level 2). A maximum of six cycles was given if a response occurred. The dose-limiting toxicity was myelosuppression, with neutropenia being more marked than thrombocytopenia. At level 2, patients experiencing a febrile-neutropenic event showed a mean 24-h urinary creatinine clearance value of 1.1 ml/s (95% confidence limits 0.8-1.4 ml/s), whereas in those who remained afebrile it was 1.7 ml/s (95% confidence limits, 1.3-2.0 ml/s). This difference was significant (P less than 0.01). Other toxicities were only mild. Creatinine clearance is a predictor of febrile episodes after treatment with high doses of CBDCA and cyclophosphamide. We are now conducting a study using human granulocyte colony-stimulating factor to reduce the incidence of neutropenia with escalating doses of these drugs in an attempt to prevent febrile events.
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PMID:Pilot study of escalating doses of carboplatin and cyclophosphamide in patients with advanced cancer. 160 May 98

Twenty-five untreated patients with extensive stage small cell lung cancer (ESSCLC) were treated with carboplatin (CBDCA) (500 mg/m2) given as a 24-hour infusion every 21 days. Thirteen patients responded for an overall response rate of 52% (95% confidence limits, 32% to 72%) with 3 complete responses (CR) (12%; 95% confidence limits, 0% to 25%). The median duration of response was 4.5 months. The median survival time was 8 months with three long-term survivors (12%) at 27, 33, and 43 months from the start of CBDCA treatment. Ninety-two courses of CBDCA were administered and one treatment-related death occurred. The main toxicity was myelosuppression. Grade 3 or 4 hematologic toxicity (hemoglobin level, less than 8 g/dl; granulocyte count, less than 1900/microliters; and platelet count, less than 49,000/microliters) was observed as follows: neutropenia in 7 courses (8%) and in 7 patients (28%), decreased hemoglobin level in 13 courses (15%) and in 7 patients (28%), and decreased platelet count in 10 courses (11%) all Grade 3 and in 8 patients (32%). This study demonstrates that at this dose and schedule CBDCA is a highly active drug in ESSCLC and it has tolerable toxicity.
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PMID:A phase II trial of carboplatin in untreated patients with extensive stage small cell lung cancer. 164 84

Thirteen patients with unresectable non small cell lung cancer were treated with radical radiotherapy and carboplatin administered concurrently. The first 6 patients were treated to a total dose of 60 Gy in 30 fractions in 6 weeks, with carboplatin 70 mg/m2/day on days 1 to 5 during weeks 1 and 5 of radiotherapy. The remaining 7 patients were given 60 Gy in 30 fractions in 3 weeks, treating twice a day (accelerated fractionation). Carboplatin was given as above but only during week 1 of radiotherapy. Twelve patients completed radiotherapy without interruption but 2 patients developed WHO grade 3 neutropenia. Major toxicity was oesophagitis, one patient requiring nasogastric feeding. Average duration of dysphagia (any grade) in the accelerated fractionation group was 21 weeks. Four patients achieved good partial responses even though initial tumour volume was large. We conclude that this treatment is associated with increased but acceptable early mucosal toxicity.
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PMID:Concurrent radiotherapy and carboplatin in non small-cell lung cancer: a pilot study using conventional and accelerated fractionation. 165 Jan 79

A total of 13 patients with metastatic carcinoid tumour, paraganglioma, or unclassified "apudoma" were treated with single-agent carboplatin at a dose of 400 mg/m2 given by intravenous infusion every 4 weeks, on the basis that this new agent shows high activity against small-cell lung cancer that also has "apudoma" characteristics. No objective tumour responses were seen. Overall, 2 patients achieved minor regression, 4/9 (44%) showed a reduction of greater than 50% in urinary 5-HIAA excretion and 8/13 (62%) reported symptomatic improvement. Treatment was well tolerated, with neutropenia and thrombocytopenia being the main toxicities. Carboplatin, like other cytotoxic agents, does not appear to have major activity against these tumours, although further studies in patients with metastatic paraganglioma are warranted.
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PMID:Carboplatin in the treatment of metastatic carcinoid tumours and paraganglioma: a phase II study. 169 Oct 51

Carboplatin (CBDCA) is a second-generation platinum drug that has been shown to be useful when used as a continuous infusion in treatment of refractory adult leukemia. We report on the effectiveness of continuous infusion CBDCA, 300 mg/m2/d x 5 days, as evaluated in nine patients with secondary acute nonlymphocytic leukemia (ANLL) (seven previous myelodysplastic syndrome and two treatment-associated ANLL), three ANLL patients in first relapse, six refractory ANLL, and nine patients with blastic phase of chronic myelogenous leukemia (BP-CML). All patients were considered assessable. The response rate was 44% (eight complete remissions [CRs], four partial remissions [PRs]). Median duration of postchemotherapy neutropenia was 36 days (range, 18 to 45). Therapy was well tolerated, and toxicity was mainly hematologic and nondose-limiting. Despite prolonged neutropenia, severe infections were rarely seen, and most patients were managed as outpatients. Twelve patients had nausea and vomiting, two had symptomatic hypomagnesemia, and one patient showed reversible ototoxicity. Because of substantial antileukemic activity and unusual extrahematologic toxicity, CBDCA appears to be an effective second-line agent in the treatment of ANLL and should be considered for upgrading to first-line treatment regimens.
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PMID:A phase II clinical trial of carboplatin infusion in high-risk acute nonlymphoblastic leukemia. 198 71

We performed a phase I-II trial of escalating doses of cisplatin (CDDP: 50-100 mg/m2 per course) plus carboplatin (CBDCA: 300-400 mg/m2 per course) as a potential way in which to maximize platinum doses without causing excessive toxic effects in patients with advanced ovarian cancer. Thirty-three patients with nonoptimally debulked disease of FIGO (International Federation of Gynecology and Obstetrics) stages IIc-IV [median age: 60 yr; median WHO (World Health Organization) performance status: 2; no prior chemotherapy] received a median of six courses of therapy. CBDCA was infused on day 1 and CDDP on day 2 with an aggressive 48-hour hydration regimen. Myelosuppression was dose-limiting: at the highest dose levels, WHO grade 4 neutropenia and thrombocytopenia led to dose reduction and/or treatment delay in 45% of the patients. Nonhematologic toxic effects included acute nausea and vomiting (97% of the patients), mild alopecia (45%), ototoxic effects (39%), neurotoxic effects (21%), and renal toxic effects (serum creatinine greater than 1.5 mg/dL: 12.5%). The pathologic complete response rate was 22%. We conclude that CBDCA and CDDP can be given safely in combination at reasonably high doses (CBDCA at 300 mg/m2 per course and CDDP at 100 mg/m2 per course) over a 6-month period, provided a close hematologic follow-up is conducted. Randomized clinical trials are needed to define whether this regimen is any better than standard combination chemotherapy.
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PMID:Cisplatin combined with carboplatin: a new way of intensification of platinum dose in the treatment of advanced ovarian cancer. Belgian Study Group for Ovarian Carcinoma. 218 Nov 52

A multi-center, open trial was conducted to determine the maximal tolerable dose of carboplatin in combination with conventional doses of both etoposide and an anthracycline for the treatment of previously untreated small cell lung cancer (SCLC) patients. Ninety-five patients [48 with limited disease (LD) and 47 with extensive disease (ED)] received a total of 376 courses of treatment. Carboplatin was given on day 1 at a dose of 250 mg m-2 in 60 courses, 300 mg m-2 in 69, 330 mg m-2 in 236 and 350 mg m-2 in 11, with 120 mg m-2 etoposide on days 1, 3 and 5 and either 40 mg m-2 adriamycin or 60 mg m-2 epirubicin on day 1. Epirubicin was not administered before carboplatin reached the dose of 330 mg m-2. Courses were repeated every 3 weeks. The main toxicity was hematological. The first course of therapy induced a dose-dependent decrease of leucocyte, neutrophil and platelet counts: all patients, except one, who received 350 mg m-2 carboplatin had a neutropenia below 200 microliters-1 and a thrombopenia below 100,000 microliters-1. Three patients died of septicemia. Other toxicities were well tolerated. After three courses, patients were re-staged by performing a mandatory fiberoptic bronchoscopy and a thoracic computed axial tomography (CAT). The overall objective response rate for 86 evaluable patients was 91% (98% for LD) with 21% complete remissions (30% for LD). All 23 hepatic and six brain sites, evaluable after chemotherapy alone, responded.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carboplatin in association with etoposide and either adriamycin or epirubicin for untreated small cell lung cancer: a dose escalation study of carboplatin. UCL Clinical Oncology Group. 255 61

Twenty-six patients with histologically proven lung cancer, treated with carboplatin at the National Cancer Center Hospital between October 1985 and October 1986, were retrospectively analyzed to determine the hematologic toxicity of carboplatin (CBDCA) and to develop guidelines for dose modification. A total of 34 courses of CBDCA were administered, of which 21 were adequate for assessment of the myelosuppression in relation to the renal function. One of three doses of CBDCA was administered by iv drip infusion over one hour (450 mg/m2, 19 courses; 400 12; 300, 3). Myelosuppression was dose-limiting, with thrombocytopenia being more sensitive than leukopenia, neutropenia or anemia. No significant correlation of the absolute count of platelets, white blood cells, polymorphoneutrophils, or hemoglobin with patient's creatinine clearance (Ccr) and dose of CBDCA administered was found. However, the percent reduction in platelets, white blood cells, polymorphoneutrophils, or hemoglobin correlated well with the relative dose of CBDCA [RD = total dose of carboplatin administered (mg/m2)/pretreatment Ccr/m2]. As thrombocytopenia was dose-limiting, we have developed an equation for modification of the dose of CBDCA from the relationship between the relative dose and percent reduction at platelet count nadir: Dosage (mg/m2) = (Ccr/m2/5.34) x [(1-desired platelet count nadir/pretreatment platelet count) x 100-12.9]. After consideration of the range of thrombocytopenia, we have further developed a simple equation to use CBDCA easily and safely: Dosage (mg/m2) = (1/10) x Ccr/m2 x desired % reduction in platelet count nadir = 10 x Ccr/m2 x (1-desired platelet count nadir/pretreatment platelet count. The clinical validity of these two equations is now being evaluated in prospective studies.
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PMID:Prediction of hematologic toxicity of carboplatin by creatinine clearance rate. 311 53


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