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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sequential chemotherapy and radiotherapy offer considerable improvements in the care of patients with locally advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Improved survival for lung cancer and organ preservation in head and neck cancer have occurred with this approach, but local control remains a problem. Concurrent chemotherapy and radiotherapy can potentially improve both local control and control of micrometastases. We previously showed that concurrent carboplatin plus radiotherapy is a useful potential treatment for advanced NSCLC and SCCHN, producing good local control and acceptable toxicity. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has recently demonstrated strong single-agent activity against both NSCLC and SCCHN. Paclitaxel has also shown favorable interactions with radiotherapy and with platinum compounds. We therefore added weekly paclitaxel at 45 mg/m2 given after premedication and before carboplatin (100 mg/m2) weekly during concurrent standard-dose radiotherapy. Twenty patients (seven with SCCHN and 13 with NSCLC) have been treated (38 and 73 weekly doses, respectively). Toxicities have been manageable with delay or dose reduction in five and eight patients, respectively, for SCCHN and NSCLC. Based on these toxicities paclitaxel dose has been reduced to 40 mg/m2/wk. Plasma pharmacokinetics have shown that concurrent carboplatin and radiotherapy do not alter the pharmacokinetic behavior of paclitaxel compared with single-agent data. Concurrent therapy with carboplatin, paclitaxel, and radiotherapy is feasible on this schedule. Further case accrual to assess efficacy is ongoing.
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PMID:Feasibility and pharmacokinetics of paclitaxel, carboplatin, and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck and for regionally advanced non-small cell lung cancer. 748 56

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

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

A phase I trial of paclitaxel therapy, administered as a weekly 3-h infusion for 6 weeks with concurrent daily thoracic radiation to patients with advanced or medically inoperable non-small cell lung cancer, was performed. Paclitaxel was escalated in increments of 10 mg/m2/week in successive cohorts of three new patients as tolerated, starting at 10 mg/m2/week. Radiation was administered to the primary tumor and regional lymph nodes (40 Gy over 4 weeks), followed by a boost to the primary tumor (20 Gy in 2 weeks). Twenty-seven patients entered this study through seven dose levels of paclitaxel ranging from 10-70 mg/m2/week for the primary purpose of evaluating the toxicity of concurrent chemoradiation treatment. Esophagitis was the principal and dose-limiting toxicity. Radiation pneumonitis occurred in two patients. Other toxicities were mild. Although not designed as an efficacy study, 23 patients were available for response, and an overall response rate of 74% (confidence interval, 65-83%) was observed.
Lung Cancer 1995 Jun
PMID:Concurrent paclitaxel and thoracic radiation for advanced non-small cell lung cancer. 755 42

The cure rate for lung cancer remains low (13%) primarily due to early systemic spread and the inability to cure systemic disease. These facts have led to pessimism regarding the role of chemotherapy, especially in non-small cell lung cancers. However, recent randomized trials demonstrated that chemotherapy significantly prolongs survival in advanced (stages IIIB and IV) and locally advanced (stages IIIA and IIIB) non-small cell lung cancers. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is an active agent in both non-small and small cell lung cancers, producing objective response rates as high as any other active agent. Early combination studies show even higher response rates when paclitaxel is combined with cisplatin or carboplatin. Ultimately, randomized trials will be needed to define the optimal use of paclitaxel and other recently developed new agents in lung cancer.
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PMID:New treatment agents for advanced small cell and non-small cell lung cancer. 759 34

The combination of ifosfamide (with mesna uroprotection), carboplatin, and etoposide (ICE) has demonstrated activity in a variety of cancers. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), a dipertene compound extracted from the Pacific yew Taxus brevifolia, appeared a good candidate for study as an addition to the ICE regimen (ICE-T) because of its broad antitumor activity, its unique mechanism of action, and its toxicity profile, which was not expected to impact the ICE regimen adversely. In a phase I study, we evaluated the impact of adding escalating doses of paclitaxel (120 mg/m2, 135 mg/m2, 150 mg/m2, and 175 mg/m2) to the ICE regimen in 13 previously untreated (with two exceptions) patients with breast cancer, sarcoma, lung cancer, and adenoid cystic carcinoma. In general, ICE-T was well tolerated with some myelosuppression observed. Responses were seen at all dose levels. To date, the maximal tolerated dose of paclitaxel has not been reached; we are currently administering 175 mg/m2.
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PMID:Phase I study of escalating doses of paclitaxel (Taxol) with fixed doses of ifosfamide, carboplatin, and etoposide. 761 Mar 96

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of paclitaxel are reviewed. Paclitaxel is a diterpenoid taxane derivative found in the bark and needles of the western yew, Taxus brevifolia. Although it shares some structural similarities with other natural alkaloids, it contains a unique taxane ring. It is also unique in that its mechanism of action involves interruption of mitosis by promoting and stabilizing microtubule formation. Paclitaxel doses greater than 60 mg/sq m i.v. consistently produce mean peak plasma concentrations of 2-13 microM. Liver metabolism and biliary excretion are probably responsible for most of the drug's elimination. In clinical trials, paclitaxel has shown substantial activity against advanced, refractory ovarian cancer, metastatic breast cancer, and lung cancer. Paclitaxel may slow the course of melanoma and is being investigated in patients with advanced head and neck cancer and gastrointestinal cancer. Neutropenia is the major dose-limiting toxic effect of paclitaxel. Other adverse effects include hypersensitivity reactions, cardiac toxicity, and neurotoxicity. The recommended dosage for the treatment of recurrent metastatic ovarian cancer is 135 mg/sq m i.v. given over 24 hours every three weeks. It is recommended that neutrophil-count and platelet-count recovery be allowed to occur before the next treatment cycle is begun. Paclitaxel's activity against refractory ovarian cancer has not been matched since the inclusion of cisplatin in treatment regimens.
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PMID:Paclitaxel: a new antineoplastic agent for refractory ovarian cancer. 769 62

Paclitaxel is the first of a new class of anticancer agents with a novel mechanism of action. Demonstration of the broad activity of this drug and its unusual effects has refocused attention on tubulin as a target for anticancer drug development. Studies are under way to identify the optimal paclitaxel dose and schedule of administration and the effective combination regimens, and to exploit the drug's radiosensitizing properties. Efforts to define pharmacodynamic relationships and clinical mechanisms of resistance and to assess other potential mechanisms for the drug's anticancer activity are also under way. In addition, other compounds that target the microtubule, some more soluble and some more potent, are in various stages of development. Phase III trials in patients with ovarian, breast, and lung cancer are continuing, and adjuvant breast cancer trials will begin soon. Such trials will establish whether paclitaxel increases the cure rate and/or survival in cancer patients.
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PMID:Taxol (paclitaxel): future directions. 786 37

Paclitaxel, a compound derived from the bark of the Pacific yew, Taxus brevifolia, is an antimitotic cytotoxic agent with a mechanism of action different from other antimitotics such as vincristine and vinblastine. Instead of causing disassembly of microtubules, paclitaxel forms extremely stable and nonfunctional microtubules, which causes inhibition of many cell functions and the interruption of the cell cycle. Procurement of paclitaxel has raised environmental concerns, leading researchers to explore a variety of approaches to obtain the drug: extraction from yew needles of a paclitaxel precursor that can be converted to paclitaxel, genetic manipulation of plants to increase yield, propagation of yew trees, semisynthesis, total chemical synthesis, and paclitaxel-producing fungus. Clinical trials involving paclitaxel have demonstrated antineoplastic effects in several classically refractory tumors: ovarian cancer, breast cancer, non-small-cell lung cancer, and head and neck tumors. Several toxic effects have been attributed to paclitaxel, including hypersensitivity reactions, cardiotoxicities, neutropenia, peripheral neuropathy, mucositis, gastrointestinal toxicities, alopecia, arthralgias, and myalgias. Clinical implications for these toxicities are addressed.
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PMID:Paclitaxel: a new antimitotic chemotherapeutic agent. 791 53

Paclitaxel (TAXOL), a novel diterpene plant product isolated from the western yew Taxus brevifolia, is an active agent in the treatment of lung cancer. In two studies, the drug produced 21% and 24% objective response rates among patients with non-small cell lung cancer. A response rate of 34% was reported in a single trial involving patients with extensive-stage small cell lung cancer. Additional trials are needed to evaluate single-agent paclitaxel in the treatment of small cell lung cancer. Studies also are planned to measure the effect of paclitaxel as a radiosensitizer and in combination regimens with other active agents for the treatment of lung cancer.
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PMID:Overview of paclitaxel (Taxol) in advanced lung cancer. 810 17


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