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)

Filgrastim, a recombinant human granulocyte colony-stimulating factor (G-CSF), has identical biological activity to that of endogenous human G-CSF, but differs in that it contains an N-terminal methionine residue and is not glycosylated. It principally stimulates activation, proliferation and differentiation of neutrophil progenitor cells and has been evaluated in the treatment of patients with various neutropenic conditions, both iatrogenic and disease-related. Two comparative studies have demonstrated that prophylactic administration of filgrastim 230 micrograms/m2/day significantly reduces the incidence, duration and severity of neutropenia in patients with previously untreated small-cell lung cancer receiving standard-dose chemotherapy with CDE (cyclophosphamide, doxorubicin plus etoposide). Concomitant with the amelioration of neutropenia, the incidence of febrile neutropenia was significantly reduced by 50% and there were 35 and 50% decreases in hospitalisation rates and intravenous antibiotic requirements. Since not all patients receiving standard-dose chemotherapy are at risk of infectious complications, prophylactic filgrastim use may be reserved for those patients who have developed febrile neutropenia during a previous cycle of the same regimen. This strategy may prove less costly, although potential savings must be weighed against a greater risk of patient morbidity and reduced quality of life. When combined with standard intravenous antibiotic therapy, filgrastim further decreases morbidity in patients with established febrile neutropenia and may have a positive impact on overall treatment costs by shortening the length of hospitalisation. Attention is focused on the use of haematopoietic growth factors to support dose-intensification of chemotherapy with a view to improving treatment outcomes in patients with chemo-responsive tumours. Filgrastim, used alone, permits modest increases in dose-intensity and/or dose-escalation of some standard-dose chemotherapy regimens. Moreover, the drug has proven useful as an adjunct to myeloablative chemotherapy followed by stem cell rescue with autologous bone marrow transplantation and/or peripheral blood progenitor cells. However, the impact of these dose-intensification approaches on survival remains to be determined in well-controlled clinical studies. Filgrastim is effective in increasing the neutrophil count and decreasing morbidity in patients with severe chronic neutropenia, including Kostmann's syndrome, and in idiopathic and cyclic neutropenia. In addition, filgrastim has accelerated neutrophil recovery in patients with idiosyncratic drug-induced agranulocytosis. Available data indicate that filgrastim is generally well tolerated. The most frequent adverse reaction is mild to moderate medullary bone pain, reported by approximately 20% of patients, although this can generally be controlled using simple analgesics without the need to discontinue treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Filgrastim. A review of its pharmacological properties and therapeutic efficacy in neutropenia. 753 Jun 30

The authors have studied the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rhG-CSF, Granulocyte Injection) on leucopenia and neutropenia induced by chemotherapy with regimen CE (Carboplatin and Etoposide) in lung cancer patients in a randomized, matched and cross-over clinical trial. The total enrolled patients were twenty-two. They were randomized into A and B groups (11 patients in each group). Each patient received two cycles treatment. In group A chemotherapy and rhG-CSF were used in the first cycle and chemotherapy alone was used in the second cycle, while in group B chemotherapy alone was used in the first cycle and chemotherapy and rhG-CSF were used in the second cycle. The results showed that rhG-CSF significantly increased the number of white blood cell (WBC) and absolute neutrophil count (ANC) at the nadir, decreased incidence of leucopenia and neutropenia, and reduced the number of days with WBC < 4.0 x 10(9)/L, ANC < 2.5 x 10(9)/L as well as the number of days with WBC > 4.0 x 10(9)/L and ANC > 2.5 x 10(9)/L. rhG-CSF ensures the completion of chemotherapy and its side-effects were slight.
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PMID:[Clinical study of recombinant human granulocyte colony-stimulating factor (RHG-CSF) on leucopenia induced by chemotherapy with CE regimen on lung cancer patients]. 754 25

A phase I study was conducted to define the maximally tolerated dose and toxicity profile of the ifosfamide/carboplatin/etoposide/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (ICE-T) regimen in advanced lung cancer. This chemotherapy program uses paclitaxel given as a 24-hour continuous infusion in conjunction with full-dose ICE chemotherapy with growth factor support. The dosage of paclitaxel was escalated from 75 to 225 mg/m2. Thirty-four patients have been accrued to date onto this study. Because hematologic dose-limiting toxicity was defined in terms of neutropenia and/or thrombocytopenia exceeding 7 days' duration, no patient demonstrated what was defined by the protocol as dose-limiting toxicity. Nonetheless, substantial hematologic toxicity was observed. Overall, 26% had fever and neutropenia, 56% had grade 4 neutropenia, and 26% had grade 4 thrombocytopenia. In all cases, hematologic toxicity was short term and reversible. While grade 3 and 4 myelosuppression was frequently observed, it was not dose related (in terms of paclitaxel dosage). Nonhematologic toxicity also was not dose related and, with only a few exceptions, was not clinically significant. Among 27 patients evaluable for response, 41% achieved an objective response, including 15% with a complete response. All of five patients with small cell lung cancer responded (including two with a complete response). Among 22 patients with non-small cell lung cancer, 27% achieved an objective response (also including two with a complete response). The results of this study suggest that with growth factor support, it is possible to safely administer full-dose, single-agent paclitaxel in conjunction with full-dose ICE chemotherapy. We will soon be initiating a phase II study of the ICE-T regimen using paclitaxel at 225 mg/m2 as a 24-hour continuous infusion in advanced lung cancer. We will also conduct a phase I study of ICE-T, with paclitaxel administered as a 3-hour continuous infusion.
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PMID:A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer. 754 29

To evaluate the efficacy of a three-drug regimen vs. a two-drug CDDP based combination in the treatment of NSCLC, we conducted a three-arm randomized parallel trial comparing (a) CDDP (120 mg/m2 day 1) + etoposide (100 mg/m2 days 1-3) every 3 weeks (PE--arm A); (b) CDDP (120 mg/m2 every 4 weeks) + mitomycin (8 mg/m2 days 1, 29, 71) + vindesine (3 mg/m2 days 1, 8, 15, 22 every 2 weeks) (MVP--arm B); and (c) CDDP (120 mg/m2 day 1) + mitomycin (6 mg/m2 day 1) + ifosfamide (3 g/m2 day 2) every 3 weeks (MIC--arm C). From May 1989 to April 1992, 393 consecutive previously untreated patients with NSCLC Stage IIIB and IV entered the trial; 373 were evaluable for survival and 360 for response. The response rate was significantly better for both the three-drug regimens compared with PE (Table 3). Logistic regression model showed a significantly better response in patients with a good P.S. and in Stage IIIB. Main toxicity consisted of myelosuppression: neutropenia Grade III-IV was recorded in 14% (arm A), 15% (arm B) and 21% (arm C). Thrombocytopenia Grade III-IV was worst in arm C: 10% vs. 5% (arm A) and 3% (arm B). Nephrotoxicity Grade III-IV was more common in arm C: 3.5%. Toxic deaths were 11 (3%: three in arm A, five in arm B, three in arm C). From our data, the three-drug containing regimens, MVP and MIC, appear more active than the two-drug combination PE in treatment of advanced NSCLC.
Lung Cancer 1995 Apr
PMID:Superiority of three-drug combination chemotherapy versus cisplatin-etoposide in advanced non-small cell lung cancer: a randomized trial by the Italian Oncology Group for Clinical Research. 755 20

Paclitaxel (Taxol), the prototype of a new class of plant-derived antineoplastic compounds, is a natural product isolated from the Pacific yew. Docetaxel (Taxotere) is a hemisynthetic product derived from the European yew. These agents share a unique mechanism of cytotoxic action by promoting assembly of microtubules and rendering the microtubules resistant to depolymerization. In vitro studies suggest a possible role for radiation sensitization. In Phase I trials, the dose-limiting toxicity was neutropenia for both agents. Other toxicities include infusion-related hypersensitivity reactions, alopecia, neurotoxicity, mucositis, diarrhoea and myalgias. To prevent infusion-related reactions, routine premedication is recommended. Noncumulative cardiac toxicity has been observed with paclitaxel. Fluid retention and rash have been reported with docetaxel. In Phase II studies of paclitaxel in advanced non-small cell lung cancer, response rates of 21% and 24% were observed. In Phase II studies of docetaxel in similar patients, response rates ranging from 28-38% were reported, including patients previously treated with cisplatin. The most common toxicity in these studies was neutropenia. Combination studies with cisplatin and other agents are in progress. Paclitaxel and docetaxel are among the most active chemotherapeutic agents for non-small cell lung cancer patients. Their testing will dominate trials of new therapies in this disease for years to come.
Lung Cancer 1995 Apr
PMID:Paclitaxel (Taxol) and docetaxel (Taxotere): active chemotherapeutic agents in lung cancer. 755 25

Camptothecin is a natural product derived from the Oriental tree Camptotheca acuminata which has shown activity in a number of experimental tumors. Its clinical development was halted in the early-70s owing to its unpredictable and formidable toxicities. Two water-soluble camptothecin analogs have been synthesized recently and are currently in clinical trials: topotecan and CPT-11. Camptothecin and its derivatives are unique in that they represent the only family of topoisomerase I inhibitors. Topoisomerase I is a nuclear enzyme which modulates the topological structure of DNA by making transient single-stranded breaks. Pre-clinical studies have shown that CPT-11 and topotecan possess high and broad antitumor activity against a variety of experimental tumors including both non-small cell lung cancer (NSCLC) and small cell lung cancer. Lack of cross-resistance with most classical anticancer agents has been also demonstrated. Phase I studies have identified neutropenia to be the dose-limiting toxicity for topotecan while, for CPT-11, either neutropenia or diarrhoea were dose-limiting. Maximum Tolerated Doses (MTD) of both agents are greatly dependent upon the schedule used. A Phase II Japanese study of CPT-11 in advanced untreated NSCLC has been recently published. Given at the dose of 100 mg/m2 as a 90-min infusion, CPT-11 produced a 32% objective response rate out of 72 assessable untreated patients. Similar studies are in progress with topotecan. The same Japanese group has completed Phase I-II studies on the combination of CPT-11 with cisplatin. The optimal dose of CPT-11, which can be safely combined with cisplatin 80 mg/m2, was found to be 60 mg/m2.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung Cancer 1995 Apr
PMID:Camptothecin analogues in the treatment of non-small cell lung cancer. 755 27

The use of preoperative chemotherapy with mitomycin, vinblastine and cisplatin (MVP) has led to improved complete resection rates and survival in Stage IIIA non-small cell lung cancer with bulky, ipsilateral, mediastinal lymph node metastases (Clinical N2 disease). The addition of preoperative irradiation has also been explored with results not substantially different from preoperative cisplatin-based chemotherapy alone. While preoperative chemotherapy has been shown to be feasible, the toxicity of both the chemotherapy and the subsequent resection is of concern with an overall treatment-related mortality of nearly 8%. The careful selection of patients, swift management of neutropenia, and meticulous perioperative pulmonary care has the potential to reduce the mortality from multimodality therapy. Having shown survival benefit in multiple single-institution and randomized trials, induction chemotherapy followed by surgery or irradiation is now the treatment of choice for patients with Stage IIIA non-small cell lung cancer with mediastinal lymph node metastases.
Lung Cancer 1995 Apr
PMID:Effectiveness and toxicity of preoperative therapy in stage IIIA non-small cell lung cancer including the Memorial Sloan-Kettering experience with induction MVP in patients with bulky mediastinal lymph node metastases (Clinical N2). 755 34

Paclitaxel is a plant product isolated from the bark of the Western yew (Taxus brevifolia) that promotes the formation and stabilization of microtubules. This leads to growth arrest in the G2/M phase of the cell cycle. Paclitaxel has demonstrated significant antineoplastic activity in different tumor types, most notably in ovarian and breast carcinoma. In two Phase II trials (Eastern Cooperative Oncology Group [ECOG]/M.D. Anderson) in patients with previously untreated Stage IIIB-IV non-small cell lung cancer (NSCLC), response rates of 21% and 24% were reported. We are performing a Phase II trial investigating the efficacy of paclitaxel in patients with inoperable Stage IIIB-IV NSCLC. Forty-three patients were treated, 31 males and 12 females, with a median age of 59 years (range, 29-75), ECOG performance status 0-2, Stage IIIB 30%, Stage IV 70%. Patients were treated every 3 weeks with 225 mg/m2 as a 3-h infusion with standard premedication. Preliminary efficacy results from 37 patients include partial remissions in eight (21.6%) patients, no change in 22 (59.5%) and disease progression in seven (19%) patients. Eight patients are still receiving therapy. The hematologic toxicities (n = 43) were mild, and no World Health Organization (WHO) Grade 4 neutropenia was observed. Nonhematologic toxicities were Grade 1/2 polyneuropathy in 97.6%, Grade 1-3 myalgia/arthralgia in 76%, and Grade 1-3 nausea/vomiting in 18.6% of the patients. In conclusion, paclitaxel is an active single agent in this patient population. Mild hematologic toxicities were observed in the 3-h infusion setting (compared with 24-h infusion) and therapy was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung Cancer 1995 Jun
PMID:Phase II study with paclitaxel for the treatment of advanced inoperable non-small cell lung cancer. 755 41

We conducted a phase I trial in advanced NSCLC to determine the optimal dosage of the new active drug paclitaxel (Taxol), in combination with high-dose ciplastin (CDDP). Taxol was infused over 3 h, followed by CDDP given over 30 min with hyperhydration. Main criteria of selection were the presence of metastatic or locally relapsing pathologically proven NSCLC, stage IIIB or IV and no prior therapy. Out of 17 treated patients, eight objective responses (47%) were documented. Significant but transient neutropenia was observed in steps III and IV. In seven patients, who received more than three courses, treatment was discontinued for severe polyneuropathy in five, cancer progression in one and unrelated disease in one. In conclusion, paclitaxel plus cisplatin, although active, was associated with severe late neurological toxicity prohibiting the administration of multiples courses.
Lung Cancer 1995 Jun
PMID:Dose-finding study of paclitaxel (Taxol) plus cisplatin in patients with non-small cell lung cancer. European Lung Cancer Working Party. 755 43

In scheduling chemotherapy and radiotherapy for locally advanced non-small cell lung cancer (NSCLC), chemotherapy can be given pre-radiotherapy or concurrently as a single agent or in combination. Optimal scheduling has yet to be established. Optimal pre-radiotherapy for NSCLC requires further development but cisplatin with vinblastine, vindesine, etoposide or navelbine appear the best currently available. A number of new drugs show potential for enhancing radiation effects. Concurrent chemotherapy and radiotherapy has been tested in a number of experimental tumours in cell culture. In these systems cisplatin, carboplatin, 5-fluorouracil, mitomycin-C and other agents appear to improve cell kill compared to chemotherapy alone. Mouse xenograft models allow the study of various concurrent drug and radiation schedules including the effect of radiation with cisplatin, carboplatin, paclitaxel and gemcitabine. In these systems, cisplatin in divided doses shows optimal enhancement with fractionated radiotherapy. There are a number of drug candidates for concurrent chemotherapy and radiotherapy programs. Clinical studies in head and neck cancer, esophageal cancer, small cell lung cancer and NSCLC show promising results with concurrent chemotherapy and radiotherapy. Cisplatin given daily with radiotherapy improved survival in NSCLC compared to cisplatin given weekly with radiotherapy or to radiotherapy alone. To study the toxicity of radiation and concurrent carboplatin, we have studied 170 patients with unresectable locally advanced NSCLC in a 4-arm randomized trial. An analysis of the first 100 patients entered revealed significantly more neutropenia (P < 0.0001) and thrombocytopenia (P < 0.004) with the combined modality arms. Esophagitis was worse on all three experimental arms but was significantly more prolonged with accelerated radiotherapy arms.(ABSTRACT TRUNCATED AT 250 WORDS)
Lung Cancer 1995 Jun
PMID:Scheduling of chemotherapy and radiotherapy in locally advanced non-small cell lung cancer. 755 50


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