Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite advances in the modalities used to treat non-small cell lung cancer (NSCLC), the frequency of locoregional and distant relapses necessitates further enhancement of the therapeutic program. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated clinical efficacy against NSCLC and in vitro studies support its role as a radiation potentiator at concentrations achievable in vivo. Thus, a phase I study of weekly paclitaxel and daily concurrent thoracic radiation was conducted in patients with advanced NSCLC to determine (1) the maximum tolerated dose of paclitaxel administered on an outpatient basis for 6 consecutive weeks with daily radiation and (2) the toxicities of the paclitaxel/radiation combination. Paclitaxel was administered as a 3-hour infusion, repeated weekly for 6 weeks with the usual premedication regimen for hypersensitivity prophylaxis. The starting dose of paclitaxel was 10 mg/m2/wk, which was increased by 10 mg/m2 in successive cohorts of three new patients, as tolerated. Radiation therapy was delivered as 40 Gy in 20 fractions to the original volume with a boost of 20 Gy in 10 fractions to the primary tumor. Doses were escalated from 10 to 70 mg/m2/wk. Of the 23 patients evaluable for response, one had stage II NSCLC, four had stage IIIA, 17 had stage IIIB, and one had stage IV. Severe esophagitis (grade 4) occurred in two of the three patients treated at 70 mg/m2 and was dose limiting. One patient discontinued therapy due to hypersensitivity, two developed grade 3 neutropenia, and one developed radiation pneumonitis. With a median follow-up of 7 months, 15 of the 23 patients remain alive. Four had a complete response and 13 had a partial response, for an overall response rate of 74% (95% confidence interval, 52% to 90%). The schedule of weekly paclitaxel and daily thoracic radiation appears active in NSCLC and can be delivered safely in the outpatient setting. The principal dose-limiting toxicity is esophagitis, and the maximum tolerated dose of paclitaxel for this schedule is 60 mg/m2/wk. A phase II trial of weekly paclitaxel 60 mg/m2 and radiation has been initiated in patients with NSCLC.
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PMID:Combined-modality therapy for advanced non-small cell lung cancer: paclitaxel and thoracic irradiation. 864 69

We have evaluated escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in combination with carboplatin, cisplatin, etoposide, and concurrent thoracic radiotherapy in patients with stage III non-small cell lung cancer. Dose-limiting toxicity was observed at paclitaxel 90 mg/m2. Subsequent modifications resulted in a new regimen, which consists of a 3-hour paclitaxel infusion on day 1 (three dose levels: 80, 100, and 120 mg/m2), etoposide 40 mg/m2 intravenously over 1 hour daily on days 2 to 5, and carboplatin given at an area under the concentration-time curve of 4 mg/mL x min on day 1 after paclitaxel. Treatment courses were repeated every 28 days. Eleven patients considered eligible for surgery received two courses. Nonsurgical patients (five) received three courses. No episodes of grade > or = 3 nausea and vomiting, dermatitis, anorexia, esophagitis, or thrombocytopenia were observed. The dose-limiting toxicity (grade 4 granulocytopenia) occurred in three of five patients at 120 mg/m2 paclitaxel (level 3). Grade 3 radiation pneumonitis was observed in three patients. Nine patients have undergone pulmonary resection: four pneumonectomies, four lobectomies, and one segmental resection. No operative deaths, respiratory insufficiency, or cardiovascular complications were observed. Clinical partial remissions have been observed in 11 of 16 patients overall, and two histologic complete remissions were achieved in nine surgical patients. Our preliminary results show that pulmonary resection is feasible following treatment with radiation and concurrent paclitaxel-containing chemotherapy. Although the maximum tolerated paclitaxel dose in the present study was relatively low, favorable initial responses warrant further study of paclitaxel-containing combination chemotherapy and concurrent radiation. We next plan to delete etoposide from our chemoradiotherapy regimen and escalate the paclitaxel dose.
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PMID:Escalating paclitaxel doses combined with carboplatin/etoposide and thoracic radiotherapy as preoperative or definitive treatment for stage III non-small cell lung cancer. 900 34

Previously untreated patients with stages IIIA or IIIB non-small cell lung cancer entered this phase II study to evaluate the activity and toxicity of combined paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin and concurrent radiation. Patients received paclitaxel 50 mg/m2/wk as a 1-hour infusion and carboplatin area under the concentration-time curve of 2/wk for 7 weeks with radiation to the primary tumor and regional lymph nodes (44 Gy) followed by a boost to the tumor (22 Gy). In addition, patients received two additional cycles of paclitaxel 200 mg/m2 and carboplatin (area under the concentration-time curve of 6) 3 weeks apart. From March 1995 to February 1996, 23 patients entered the study and their overall response rate (complete plus partial responses) was 82%. The major toxicity was esophagitis. Nine patients (45%) had experienced grades 3 or 4 esophagitis by the end of the 7-week concurrent phase. Seven of the nine patients recovered from the esophagitis within 2 weeks and received the additional two cycles of paclitaxel 200 mg/m2 and carboplatin (area under the concentration-time curve of 6). Only one patient (4%) had grade 4 pneumonitis; this patient also recovered within 2 weeks and received the final two doses of combined chemotherapy. Therapy with paclitaxel, carboplatin, and concurrent radiation is a promising treatment for patients with locally advanced non-small cell lung cancer; it has a high response rate and acceptable toxicity.
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PMID:Paclitaxel plus carboplatin and concurrent radiation therapy for patients with locally advanced non-small cell lung cancer. 900 37

The goal of this National Cancer Institute-sponsored phase I trial is to determine the feasibility, toxicity, and pharmacokinetics of continuous-infusion (24 hr/d, 7 d/wk, 7 weeks total) intravenous paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) when combined with standard, curative-intent radiation therapy (RT) for previously untreated, locally advanced non-small cell lung cancers. Eligible patients have locally advanced (T4NXM0 or TXN2-3M0) non-small cell cancer ineligible for potentially curative surgical resection, a good performance status, adequate hematologic, hepatic, and renal functions, and no distant metastases. All patients receive a total tumor dose of 64.8 Gy megavoltage RT in 7 weeks at 1.8 Gy once daily, 5 d/wk. Paclitaxel is delivered by continuous intravenous infusion starting 48 hours before RT and continuing for its duration. The dose of paclitaxel is escalated in cohorts of three patients in a standard phase I design. To date, 16 patients have entered the trial, and 15 are evaluable for toxicity in this ongoing study. Paclitaxel dose is currently at a 6.5 mg/m2/d dose level, with no dose-limiting toxicity recorded thus far. One patient at the highest dose level has had grade 2 pneumonitis. With the exception of anemia, toxicities are those that would be expected from RT alone. A slowly progressive normocytic anemia with no renal dysfunction was found to be associated with an acquired hypoerythropoietin state. These findings indicate that this therapy is feasible and well tolerated through current dose levels, with no dose-limiting toxicity. Dose escalation is ongoing.
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PMID:Seven-week continuous-infusion paclitaxel plus concurrent radiation therapy for locally advanced non-small cell lung cancer: a phase I study. 933 Nov 30

This report summarizes results from a series of pilot trials using combined-modality chemoradiotherapy with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) as a radiosensitizing agent in patients with cancers of the lung, cervix, and bladder. In a phase I study of paclitaxel/radiotherapy in patients with locally advanced non-small cell lung cancer, five paclitaxel dose levels were evaluated in conjunction with simultaneous radiation (total dose, 59.4 Gy). A minimum of five patients were treated at each dose level; paclitaxel doses ranged from 45 mg/m2 over 3 weeks (level 1) to 65 mg/m2 for 7 weeks. Of 34 enrolled patients, 25 are evaluable for toxicity and response. Side effects were generally moderate for this combined-modality therapy, although two patients at level 5 developed dose-limiting toxicities (grade 4 esophagitis and grade 3 pneumonitis). Among 25 evaluable patients, complete and partial response rates were 4% (one patient) and 64% (16 patients), respectively; eight patients had a minor response. Median survival was 6 months (range, 1 to 20 months). Therapy was well tolerated, suggesting that the combined modalities offer a practical, effective therapy for patients with non-small cell disease. A paclitaxel dose of 55 mg/m2 is recommended for further study of combined-modality chemoradiotherapy in this clinical setting. In another trial, 33 women with inoperable, locally advanced cervical cancer received carboplatin 50 mg/m2 via intravenous infusion simultaneously with external-beam radiation therapy and vaginal brachytherapy, to define the regimen's toxicity and safety. Among the 33 women, 78% achieved a complete response to therapy. The investigators next conducted a trial of paclitaxel 50 mg/m2 given weekly over 3 hours with the previous carboplatin/radiotherapy regimen in four women and documented two partial responses, one near-complete response, and one minor response, with moderate, manageable toxicity. In a final case report on a patient with recurrent bladder cancer, simultaneous radiotherapy and weekly paclitaxel 50 mg/m2 intravenously over 3 hours yielded a partial remission, prompting the investigators to plan a phase I study to confirm the regimen's efficacy and safety. Additional planned studies include a phase I trial of simultaneous chemoradiotherapy in patients with cancer of the head and neck.
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PMID:Simultaneous paclitaxel and radiotherapy: initial clinical experience in lung cancer and other malignancies. 933 Nov 31

We previously observed encouraging results and acceptable toxicity in phase II trials testing preoperative split-course thoracic radiation and simultaneous cisplatin, etoposide, and 5-fluorouracil in stage III non-small cell lung cancer patients. We decided to delete 5-fluorouracil and to incorporate paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into our combined-modality treatment. The first group of patients received carboplatin dosed at an area under the concentration-time curve of 4 on day 2, etoposide 50 mg orally days 1 to 5 and 8 to 12, cisplatin 50 mg/m2 on day 21, and paclitaxel 35 mg/m2 escalated to 45 mg/m2 on days 1 and 8. Group 2 patients received carboplatin dosed at an area under the concentration-time curve of 4 on day 1, etoposide 45 mg/m2 intravenously daily on days 2 to 5, and paclitaxel 80 mg/m2 (escalating to 120 mg/m2) on day 1. Patients in group 3 received carboplatin dosed at an area under the concentration-time curve of 4 on day 1 and paclitaxel 120 mg/m2 (escalating to 140 mg/m2) on day 1. Each patient received radiation 2 Gy daily on days 1 to 5 and 8 to 12, and a total of two cycles was given at 28-day intervals. Twenty-one patients received preoperative chemoradiotherapy: group 1, five patients; group 2, 11 patients; and group 3, five patients. Thoracotomy was not done in five patients due to cerebrovascular accident in one and progressive tumor in four. The remaining 16 patients had the following procedures: pneumonectomy, eight; lobectomy, six; chest wall resection, one; and no resection, one. Postoperative complications included bronchopleural fistula in one patient each in groups 1 and 3, hypoxia in one patient in group 1, pulmonary hypertension in one patient in group 2, pneumonia in one patient in group 2, and adult respiratory distress syndrome in one patient in group 3, which proved lethal. Thus, six of 16 patients had serious postoperative complications. The relatively high incidence of postoperative bronchopulmonary complications suggests that the use of preoperative paclitaxel-containing chemotherapy and simultaneous thoracic radiation may not be feasible.
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PMID:Postoperative bronchopulmonary complications in stage III lung cancer patients treated with preoperative paclitaxel-containing chemotherapy and concurrent radiation. 933 Nov 36

To evaluate the safety and efficacy of weekly low-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in patients with refractory cancer, participating subjects received standard prophylactic medication followed by intravenous paclitaxel once a week for 3 weeks every 4 weeks. The 50-mg/m2 starting dose was increased by 10 mg/m2 for every five patients, as long as no dose-limiting toxicity had occurred in more than two of five patients treated at the preceding level. Eligibility criteria included metastatic and refractory malignant disease; an Eastern Cooperative Oncology Group performance status of 0, 1, or 2; and adequate hematologic, hepatic, and renal functions. Of 30 patients treated and evaluable for toxicity, 25 were evaluable for response. The majority of patients tolerated the treatment very well. In a total of 114 cycles, the worst toxicities observed were leukopenia (one grade 4, two grade 3), granulocytopenia (one grade 3, one grade 4), anemia (one grade 3, two grade 2), and infection (one grade 5, one grade 3). Three patients had grade 2 gastrointestinal toxicity and three had grade 1 peripheral neuropathy. Only one dose-limiting toxicity, at 100 mg/m2, has occurred. This patient died of bilateral pneumonia with neutropenia. We have observed partial responses in seven of 12 patients with breast cancer and three of eight with non-small cell lung cancer. The study remains open at the current dose level of 100 mg/m2/wk. Weekly low-dose paclitaxel is well tolerated and efficacious. Further phase II studies are warranted, to continue evaluation of this schedule of paclitaxel either alone or in combination with other drugs active in paclitaxel-responsive diseases.
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PMID:Dose-escalation study of weekly 1-hour paclitaxel administration in patients with refractory cancer. 937 98

Adjuvant therapy in non-small cell lung cancer has become a controversial topic during this present decade. Postoperative thoracic irradiation has the potential to decrease local recurrence and lessen the probability of postobstructive pneumonia or atelectasis. However, as a single modality, in several randomized studies, it has failed to have a favorable impact on survival. Most postoperative adjuvant chemotherapy studies, likewise, have not improved survival compared with operation alone. Recently, there has been a resurgence of interest in preoperative (neoadjuvant) chemotherapy in clinical stage IIIA disease, based on two very positive, albeit small, phase III studies. Improved chemotherapy in stage IV disease using newer and more effective agents, such as vinorelbine (Navelbine), paclitaxel (Taxol), or gemcitabine (Gemzar), is now available. It is hoped that the modest gains in stage IV disease can translate to more significant improvement in earlier stage disease.
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PMID:Neoadjuvant and adjuvant trials in non-small cell lung cancer. 969 1

Bronchioloalveolar carcinoma (BAC) is a previously uncommon subset of non-small cell lung cancer (NSCLC) with unique epidemiology, pathology, clinical features, radiographic presentation, and natural history compared with other NSCLC subtypes. Recent data suggest that the incidence of BAC is increasing, notably in younger nonsmoking women. Despite reports of prolonged survival after repeated surgical resection of multifocal lesions and slow growth kinetics, advanced bilateral or recurrent diffuse BAC remains incurable, with the vast majority of patients dying of respiratory failure or intercurrent pneumonia within 5 years. Limited data suggest that chemotherapy may yield poor results in BAC. However, anecdotal reports of prolonged complete response to tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR), a member of the human epidermal growth factor receptor (erbB) family, have raised considerable interest in studying this NSCLC subset. Here we present clinical data and preliminary results of correlative science studies analyzing human epidermal growth factor receptor pathways from the following two prospective Southwest Oncology Group clinical trials performed in advanced stage BAC: S9714 testing a 96-h continuous infusion of paclitaxel (Taxol) and S0126 evaluating the small molecule EGFR inhibitor gefitinib (ZD1839 or Iressa). These studies provide a biological rationale for investigating BAC as a model of predictive markers of EGFR inhibition.
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PMID:Bronchioloalveolar carcinoma: a model for investigating the biology of epidermal growth factor receptor inhibition. 1521 59