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

The purpose of the study was to delineate the efficacy and toxicity of paclitaxel (Taxol, Bristol Myers Squibb) in the treatment of drug resistant small-cell lung cancer (SCLC). Patients with SCLC relapsing within 3 months of cytotoxic therapy received paclitaxel 175 mg m(-2) intravenously over 3 h every 3 weeks. The dose of paclitaxel was adjusted to the toxicity encountered in the previous cycle. Of 24 patients entered into the study, 24 and 21 were assessable for response and toxicity respectively. There were two early deaths and two toxic deaths. No complete and seven partial responses (29%) (95%CI 12-51%) were observed and five patients had disease stabilization. The median survival (n = 21) was 100 days. Life-threatening toxicity occurred in four patients; in others (non)-haematological toxicity was manageable. Paclitaxel is active in drug-resistant SCLC. Further investigation in combination with other active agents in this poor prognosis group is appropriate.
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PMID:A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. 946 Oct 9

Paclitaxel and docetaxel are 2 compounds from the new taxoid class of anti-cancer agents. Both drugs are very similar in preclinical activity, mechanism of action and spectrum of clinical activity. Some subtle differences in the intracellular retention of docetaxel may account for its lack of schedule-related myelosuppression and greater potency, and may be relevant to the skin toxicity and oedema which it produces. Early data suggest that there may be differing behaviour of anthracycline/taxoid combinations with respect to cardiotoxicity. Paclitaxel has been studied in several first-line combination therapy trials in ovarian cancer. Here, paclitaxel in combination with a platinum compound seems to have proven itself as a standard regimen. It is uncertain if docetaxel will be evaluated in this context. An abundance of clinical data is available for both analogues in the advanced, metastatic setting of breast cancer. Both also have been compared as single agents with doxorubicin with the results suggesting paclitaxel in a 3-hour infusion is inferior to the anthracycline (in terms of response rate), and those of docetaxel suggesting it is superior to the same dose of doxorubicin. This indirect comparison favours the activity of docetaxel; however, it is clear that in the dose/schedules studied, the taxoid compounds are not equitoxic. Either agent by itself, in the treatment of metastatic breast cancer, remains appropriate; however, lack of cumulative toxicity may make paclitaxel more attractive in some situations where prolonged administration is foreseen. Lung cancer trials have also confirmed the activity of both agents, although docetaxel appears to have slightly more promising activity in previously treated patients than paclitaxel. Paclitaxel in combination with cisplatin has been evaluated in randomised trials as first-line treatment of non-small-cell lung cancer (NSCLC). The results of these trials taken together suggest that this combination has an impact on survival similar to other new regimens now considered 'standard' in the front-line setting in this disease. Unfortunately, despite all the phase II data generated in numerous tumour types, little else can be said about the role of either taxoid in the 'standard' management of malignant disease. It will be some years yet before taxoid-based combinations have been evaluated sufficiently in randomised trials such that the impact of this novel class can be adequately assessed in terms of survival and cure rates.
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PMID:The taxoids. Comparative clinical pharmacology and therapeutic potential. 946 87

We examined paclitaxel for anti-tumor activity against human lung cancer xenografts in nude mice and compared its efficacy with that of cisplatin, currently a key drug for lung cancer chemotherapy. Five non-small cell lung cancers (A549, NCI-H23, NCI-H226, NCI-H460 and NCI-H522) and 2 small cell lung cancers (DMS114 and DMS273) were chosen for this study, since these cell lines have been well characterized as regards in vitro and in vivo drug sensitivity. These cells were exposed to graded concentrations of paclitaxel (0.1 to 1000 nM) for 48 h. The 50% growth-inhibitory concentrations (GI50) for the cell lines ranged from 4 to 24 nM, which are much lower than the achievable peak plasma concentration of paclitaxel. In the in vivo study, 4 cell lines (A549, NCI-H23, NCI-H460, DMS-273) were grown as subcutaneous tumors xenografts in nude mice. Paclitaxel was given intravenously as consecutive daily injections for 5 days at the doses of 24 and 12 mg/kg/day. Against every xenograft, paclitaxel produced a statistically significant tumor growth inhibition compared to the saline control. Paclitaxel at 24 mg/kg/day was more effective than cisplatin at 3 mg/kg/day with the same dosing schedule as above, although the toxicity of paclitaxel was similar to or rather lower than that of cisplatin, in terms of body weight loss. In addition, paclitaxel showed potent activity against 2 other lung cancer xenografts (NCI-H226 and DMS114). Therefore, paclitaxel showed more effective, wider-spectrum anti-tumor activity than cisplatin in this panel of 6 lung cancer xenografts. These findings support the potential utility of paclitaxel in the treatment of human lung cancer.
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PMID:Anti-tumor efficacy of paclitaxel against human lung cancer xenografts. 947 39

Paclitaxel is a new antineoplastic agent with activity in lung cancer. This phase I clinical trial was designed to determine the maximum tolerated dose (MTD) of paclitaxel in combination with etoposide in previously untreated patients with non-small cell lung cancer (NSCLC). Doses of paclitaxel were in the range of 150-225 mg/m2 (d1) and of etoposide in the range of 100-120 mg/m2 (d2-4). The drugs were administered by i.v. infusion over 3 h (paclitaxel) and 2 h (etoposide). The patients received four courses at 21-day intervals. Twenty-four patients (six female, 18 male) entered the trial. The characteristics of the patients were as follows: median age 64 (55-73) years; Karnofsky index 80% (70-90%); stage IIIB n = 7, IV n = 17; histology, 14 adenocarcinoma, 10 squamous carcinoma. Hypersensitivity reactions after paclitaxel were not observed. The most relevant toxic effect observed was neutropenia (WHO grade 3-4). Three episodes of febrile neutropenia, two episodes of absolute neutropenia (< 100/microliter for > 3 days), and one case of mucositis (WHO grade > or = 3 for > 7 days) occurred. It can be concluded that the MTD of paclitaxel in combination with etoposide was reached at doses of 200 mg/m2 paclitaxel (d1) and 100 mg/m2 etoposide (d2-4).
Lung Cancer 1998 Jan
PMID:A phase I study of paclitaxel in combination with etoposide in patients with stage IIIB/IV non-small cell lung cancer (NSCLC). 949 38

We report here the preliminary results of a large phase II multicenter study done in the community setting, using paclitaxel (Taxol) (given by 1-hour infusion) plus carboplatin (Paraplatin) to treat patients with advanced non-small-cell lung cancer (NSCLC). In this study, 155 chemotherapy-naive patients with stage IIIB, stage IV, or recurrent metastatic non-small-cell lung cancer received the two drugs in 21-day cycles. Paclitaxel 225 mg/m2 was given by 1-hour intravenous infusion followed immediately by carboplatin at a targeted area under the concentration-time curve of 6.0 (calculated according to the Calvert formula). Colony-stimulating factors were not used routinely. Objective responses occurred in 53 of 155 patients (34%) (53 of 144 [36%] evaluable patients) including three complete responses and 50 partial responses. Fifty-two other patients had stable disease at initial reevaluation. The median survival among all 155 patients was 8 months; the 1-year survival rate was 42%, and the 2-year survival rate was 20%. Leukopenia and cumulative peripheral neuropathy occurred consistently but rarely were severe or affected the course of therapy. One patient died due to sepsis. Other grade 3 and grade 4 toxicities were uncommon. This paclitaxel-carboplatin combination chemotherapy appears to be a relatively convenient, safe, and active regimen in advanced non-small-cell lung cancer.
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PMID:One-hour paclitaxel plus carboplatin for advanced non-small-cell lung cancer. 951 16

Non-small-cell lung cancer (NSCLC) will increasingly come under better control as the current approaches to therapy are more broadly employed and as new therapies are deployed against recently elucidated molecular pathways. In the United States, real progress is finally being made in decreasing tobacco consumption and in lung cancer incidence. The traditional chemotherapeutic compounds that became available earlier this decade (paclitaxel [Taxol], docetaxel [Taxotere], gemcitabine [Gemzar], vinorelbine [Navelbine], irinotecan [Camptosar], topotecan [Hycamtin], and edatrexate) have all been tested as single agents and as doublets with cisplatin (Platinol) and carboplatin (Paraplatin). Paclitaxel with cisplatin or carboplatin and vinorelbine, docetaxel, or gemcitabine with cisplatin have all demonstrated significant activity that now appears clearly better than the prior standard therapy of etoposide (VePesid)/cisplatin. Phase III studies sorting out their benefit relative to each other should be completed in the next 1 to 2 years. To date, no triplet therapy appears better than the corresponding doublet. Non-platinum-containing doublets are just completing their first round of assessments. Aside from new drugs and applications, the use of "small" molecules to inhibit either signal transduction pathways or gene activation is likely to accelerate. Most of the newer chemotherapeutic agents can be interdigitated with radiation and surgery, although evaluations into sequence and dose issues continue. The superior outcomes seen with the newer regimens should translate to the adjuvant and preoperative or preradiotherapy settings relatively quickly. It is now clear that NSCLC is as responsive to therapy as small-cell lung cancer (SCLC) and that outcomes are superior for NSCLC. The enthusiasm for treating SCLC displayed by nononcologists and nonthoracic medical oncologists should be shared for NSCLC.
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PMID:Future directions in non-small-cell lung cancer: a continuing perspective. 951 20

The authors define the dose-limiting toxicities and the recommended phase II doses of paclitaxel combined with etoposide, without and with filgrastim support. Patients with advanced solid tumors were eligible if they had a performance status of 0 to 2 and normal renal, hepatic, and bone marrow function. Patients with cardiac arrhythmias or congestive heart failure requiring medical therapy were excluded. Prior radiation was allowed only if it involved less than 30% of the marrow-containing skeleton. The dose of etoposide was fixed at 100 mg/m2/d for 3 days beginning on day 1. Paclitaxel was administered over 3 hours on day 4. The dose of paclitaxel was escalated until the maximum tolerated dose (MTD), without and with filgrastim 5 microg/kg (or 300 microg total dose) subcutaneously beginning on day 5, was reached. Treatment cycles were repeated every 21 days. Of 39 patients entered, 37 were evaluable for toxicity and 30 for response. The principal toxicity was neutropenia. Without filgrastim, the MTD of paclitaxel was 150 mg/m2. With filgrastim, the dose of paclitaxel was escalated to 250 mg/m2 in combination with etoposide 100 mg/m2. One episode of pulmonary toxicity was observed. Five patients responded: two with previously treated non-small-cell lung cancer (NSCLC), two with refractory small-cell lung cancer (SCLC), and one with refractory germ-cell tumor (GCT). We conclude that paclitaxel and etoposide can be given in combination at clinically relevant doses with filgrastim support. In this phase I trial, a dose of paclitaxel of 200 mg/m2 on day 4 and etoposide at 100 mg/m2/d on days 1-3, with filgrastim 5 microg/kg beginning on day 5, was found to be well tolerated, and can be recommended for future studies. Without filgrastim, a paclitaxel dose of 150 mg/m2 with the same dose of etoposide can also be recommended.
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PMID:Phase I study of paclitaxel and etoposide for metastatic or recurrent malignancies. 953 96

Paclitaxel and irinotecan are important new anticancer agents. The combination of these two agents has been considered for use against a variety of advanced solid tumors. Since the schedule-dependent effects of this combination may be crucial to its use, we studied the interaction of paclitaxel and SN-38 (the active metabolite of irinotecan) in various schedules in four human cancer cell lines in culture. Cell growth inhibition after 5 days was determined using an MTT assay. The effects of drug combinations at the IC80 level were analyzed by the isobologram method. Simultaneous exposure to paclitaxel and SN-38 for 24 h produced antagonistic (subadditive and protective) effects in the human lung cancer cell line A549, the breast cancer cell line MCF7, and the colon cancer cell line WiDr, and produced additive effects in the ovarian cancer cell line PA1. Sequential exposure to paclitaxel for 24 h followed by SN-38 for 24 h, and the reverse sequence, produced additive effects in all four cell lines. These findings suggest that sequential administration, not simultaneous administration, may be the appropriate schedule for the therapeutic combination of paclitaxel and irinotecan. Continued preclinical and clinical studies should provide further insights and assist in determining the optimal schedule for this combination in clinical use.
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PMID:In vitro schedule-dependent interaction between paclitaxel and SN-38 (the active metabolite of irinotecan) in human carcinoma cell lines. 965 7

On the basis of the safety of the 1-h paclitaxel infusion schedule in prior studies we attempted to evaluate the feasibility of a shorter infusion schedule (< 1-h), given the general lack of published data or of attempts at applying this strategy. Before receiving paclitaxel, all patients were premedicated with promethazine, dexamethasone, and ranitidine; they were then given paclitaxel at a dose of 175 mg/m2 diluted in 150 ml normal saline. Four patients were evaluated, two with breast cancer, one with ovarian carcinoma, and one with non-small-cell lung cancer. All had received at least two prior cycles of paclitaxel and had never exhibited any hypersensitivity reaction. In all four patients, adverse signs and symptoms were observed at 5-15 min after the start of paclitaxel administration. These included generalized erythema (three patients), angioedema (all patients), sinus tachycardia (all patients), dyspnea (all patients), and increased sweating (all patients). One patient experienced acute diarrhea. Significant changes in vital signs were recorded in all patients, but there was no dysrhythmia or syncope. Thereafter, drug infusion was interrupted and supportive measures were initiated with dimethidene maleate, ranitidine, and methylprednisolone. In all patients, symptoms resolved over the next 15-30 min, and paclitaxel was reinstituted at the standard 1-h rate with no further sequelae. Paclitaxel administration in < 1 h did not prove to be safe in the current pilot experience and, therefore, cannot be recommended.
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PMID:Risk of severe acute hypersensitivity reactions after rapid paclitaxel infusion of less than 1-h duration. 978 79

Paclitaxel blocks cells in G2-M, and this may result in a schedule-dependent effect on paclitaxel cytotoxicity. To test this hypothesis, we evaluated paclitaxel cytotoxicity in 28 human lung cancer cell lines. Fourteen of the cell lines were derived from patients with non-small cell lung cancer (NSCLC), and 14 were from patients with small cell lung cancer (SCLC). All cell lines were exposed to a range of paclitaxel concentrations for durations of 3, 24, and 120 h, and cytotoxicity was measured with a tetrazolium-based assay. The median IC50 values for all 28 cell lines at exposure durations of 3, 24, and 120 h were >32 microM, 23 microM, and 0.38 microM, respectively. The median IC50 values for the NSCLC cell lines were >32 microM, 9.4 microM, and 0.027 microM at exposure durations of 3, 24, and 120 h, respectively. For the 14 SCLC cell lines, the median IC50 values were >32 microM, 25 microM, and 5.0 microM, respectively. Five of the 14 SCLC cell lines had IC50 values at 120 h of paclitaxel exposure that were 1000-fold less than the remaining SCLC cell lines. The median IC50 values for these five sensitive SCLC cell lines at 3-, 24-, and 120-h exposures were >32 microM, 23 microM, and <0.0032 microM, respectively. These in vitro cytotoxicity results were independent of the paclitaxel diluent, a 1:1 solution of ethanol and Cremophor EL. We conclude that longer durations of paclitaxel exposure result in an increase in the chemosensitivity of some human lung cancer cell lines and that this phenomenon is more consistent within NSCLC cell lines than in SCLC cell lines.
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PMID:Paclitaxel cytotoxicity against human lung cancer cell lines increases with prolonged exposure durations. 981 4


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