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 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the TAX 326 trial, 1,220 chemotherapy-naive patients with advanced or metastatic non--small cell lung cancer have been randomized to receive one of three regimens: docetaxel 75 mg/m(2) plus cisplatin 75 mg/m(2) every 3 weeks; docetaxel 75 mg/m(2) plus carboplatin to an area under the curve of 6 mg/mL x min every 3 weeks; or a control arm of vinorelbine 25 mg/m(2) weekly plus cisplatin 100 mg/m(2) monthly. The treatment and toxicity data presented are based on a planned preliminary analysis conducted after 601 patients had been enrolled. The median age of patients randomized was 60 years and 73% were male. The majority of patients had a Karnofsky score of 80 or greater, two thirds had stage IV disease and 35% had three or more sites of organ involvement. While the relative dose intensity for docetaxel was 0.97 both when combined with cisplatin and when combined with carboplatin, the corresponding figure for vinorelbine was 0.68, reflecting the frequent need for dose reduction when combined with cisplatin on the schedule used. Hematologic toxicities were tolerable and comparable across the three arms of the trial, and the rate of febrile neutropenia was below 5% in all cases. The incidence of nonhematologic toxicities also was similar, although nausea and vomiting appeared to be less frequent among patients assigned to docetaxel plus carboplatin than among patients receiving comparator regimens. Semin Oncol 28 (suppl 9):10-14.
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PMID:Phase III randomized trial of docetaxel in combination with cisplatin or carboplatin or vinorelbine plus cisplatin in advanced non--small cell lung cancer: interim analysis. 1144 9

Non-platinum combination regimens have been developed for advanced non--small cell lung cancer using the novel and active agents docetaxel, gemcitabine, vinorelbine, and irinotecan. The aim of these combinations is to equal or exceed the survival benefits achieved with cisplatin doublets while minimizing toxicity. Of the docetaxel-based combinations, gemcitabine has been the most extensively studied. In a 317-patient randomized trial, docetaxel plus gemcitabine achieved a response rate of 34%, similar to the 32% response rate seen in patients randomized to docetaxel plus cisplatin. One-year survival rates were 38% and 42%, respectively. While being equally active, the docetaxel/gemcitabine combination was associated with significantly less neutropenia and gastrointestinal adverse events than the cisplatin-containing regimen. Phase II trials of docetaxel plus vinorelbine have reported response rates of up to 51% and 1-year survival in up to 60% of patients without significant peripheral neuropathy. Docetaxel plus irinotecan is also active in advanced non--small cell lung cancer and has shown similar efficacy to docetaxel plus cisplatin in a randomized trial. The adverse event profile of docetaxel/irinotecan is different from that of cisplatin-based regimens. Both non-platinum and platinum combination regimens have an important role to play in the treatment of non--small cell lung cancer. Semin Oncol 28 (suppl 9):15-20.
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PMID:Non-platinum based combination chemotherapy: phase I and II trials of docetaxel plus gemcitabine, vinorelbine, or irinotecan. 1144 10

Administering docetaxel weekly at a relatively low dose minimizes myelosuppression and reduces nonhematologic toxicities. In a community-based phase II trial conducted in 39 elderly or poor performance status patients with advanced non--small cell lung cancer, weekly 36 mg/m(2) docetaxel produced a response rate of 20%. The response rate was 26% in patients with an Eastern Cooperative Oncology Group performance status of 0 or 1. Actual 1-year survival was 28% and actuarial 2-year survival was 15%. These results are similar to those achieved with other active single agents. The regimen of weekly docetaxel used was associated with minimal hematologic toxicity. There were no cases of grade 4 leukopenia, febrile neutropenia, toxicity-related hospital admissions, or treatment-related death. Nonhematologic toxicities were also mild, even in performance status 2 patients. In a subsequent phase II trial, a similar group of patients received weekly docetaxel at 30 mg/m(2) plus weekly gemcitabine 800 mg/m(2), both drugs given on days 1, 8, and 15 every 28 days. Preliminary analysis of data for the first 41 patients enrolled show an objective response rate of 29%, with an additional 45% of patients having stable disease. Although 26% of patients missed the day 15 dose of gemcitabine and docetaxel because of myelosuppression, the combination regimen was generally well tolerated. There were no hospitalizations caused by complications of myelosuppression. One patient developed bilateral pulmonary infiltrates, possibly treatment-related, and died of respiratory failure. Further evaluation of weekly docetaxel-based combinations is indicated. Semin Oncol 28 (suppl 9):21-25.
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PMID:Weekly docetaxel as a single agent and in combination with gemcitabine in elderly and poor performance status patients with advanced non--small cell lung cancer. 1144 11

Randomized phase III studies reported this year prove that docetaxel is superior both to best supportive care (BSC) and to a standard regimen of vinorelbine or ifosfamide as second-line therapy for advanced non--small cell lung cancer. In a landmark study authored by Dr Frances Shepherd, 204 patients with stage IIIB/IV non--small cell lung cancer who had failed previous cisplatin-based chemotherapy were randomized to receive either docetaxel (100 mg/m(2) or 75 mg/m(2) every 3 weeks) or BSC. The median survival of patients assigned to docetaxel was 7.6 months, significantly longer than the median of 4.6 months in patients treated with BSC alone. The rate of febrile neutropenia was 22% in patients receiving 100 mg/m(2) docetaxel but only 1.8% when the dose was 75 mg/m(2). Patients treated with docetaxel required less additional opioid analgesia and palliative radiotherapy than those receiving BSC. Patients in the docetaxel 75 mg/m(2) arm also were significantly less likely to lose 10% or more body weight and to experience severe fatigue. In a second phase III study led by Dr Frank Fossella, 373 patients were randomized to docetaxel 100 mg/m(2), docetaxel 75 mg/m(2), or a control arm of vinorelbine 30 mg/m(2) or ifosfamide 2 g/m(2). Median survival was similar between the two groups (range, 5.5 to 5.7 months). However, the survival rate at I year was significantly higher in patients assigned to 75 mg/m(2) than in the control arm. Patients receiving docetaxel 75 mg/m(2) experienced better global quality of life (Lung Cancer Symptom Scale: patient-rated) than patients receiving vinorelbine or ifosfamide. A higher incidence of grade 4 neutropenia and febrile neutropenia was observed in the docetaxel arms of the study, but the incidence of infections was low and nonhematologic toxicities were similar across all treatment arms. These studies show docetaxel provides meaningful survival and clinical benefits in second-line non-small cell lung cancer. The dose recommended in this setting is 75 mg/m(2) every 3 weeks.
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PMID:Review of two phase III randomized trials of single-agent docetaxel in previously treated advanced non--small cell lung cancer. 1144 53

Small cell lung cancer is a chemosensitive disease; however, patients with extensive-stage disease or adverse prognostic factors are rarely cured. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a new agent with good tolerability, interacts synergistically with platinum agents. Carboplatin is as effective as cisplatin, but is less toxic. The London Lung Cancer Group is conducting a multicenter, open-label, randomized, phase III trial in patients with histologically or cytologically proven small cell lung cancer and extensive-stage, limited-stage but locally-advanced, or limited-stage disease with poor prognostic factors. Chemotherapy consists of 21-day cycles of gemcitabine 1,200 mg/m(2) intravenous (IV) on days 1 and 8, plus carboplatin area under the curve of 5 IV on day 1, or cisplatin 60 mg/m(2) IV on day 1 plus etoposide 120 mg/m(2) IV on day 1 and 100 mg orally on days 2 and 3. Thirty-nine patients have been randomized to gemcitabine/carboplatin and 38 to cisplatin/etoposide (23 and 22 completed treatment, with 96 and 84 cycles, respectively). Preliminary toxicity data indicate hematologic toxicity in 25% of cycles for gemcitabine/carboplatin and 16% for cisplatin/etoposide, although cisplatin/etoposide-treated patients experienced significant alopecia, nephrotoxicity, nausea and vomiting, and neutropenia. This London Lung Cancer Group trial of gemcitabine/carboplatin may define an active, safe, and acceptable treatment for patients with extensive-stage and poor-prognosis small cell lung cancer. Semin Oncol 28 (suppl 10):15-18.
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PMID:Gemcitabine/carboplatin versus cisplatin/etoposide for patients with poor-prognosis small cell lung cancer: a phase III randomized trial with quality-of-life evaluation. 1151 29

Eighteen elderly patients aged 76 years or older with small cell lung cancer were treated with carboplatin (AUC = 4 mg/ml.min, i.v. day 1) and etoposide (70 mg/m2 i.v. day 1-3) and 17 patients were evaluable. The median age of the study population was 77 years (range: 76-81). Eight patients had limited disease (LD) and nine did extensive disease (ED). The overall response rate was 88% for LD patients and 67% for ED patients. Median survival time was 219 days for LD patients and 158 days for ED patients. Grade 3 and 4 leukopenia, neutropenia, thrombocytopenia and anemia occurred in 41%, 76%, 24% and 6% of patients, respectively. There was one treatment-related death due to pneumonitis.
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PMID:[Combination chemotherapy with carboplatin and etoposide for elderly patients aged 76 years or older with small cell lung cancer]. 1204 Jun 79

Topotecan is a topoisomerase-I inhibitor, a drug that stabilizes a covalent complex of enzymes and causes strand cleavage of DNA. 5-Fluorouracil (5FU) is an antimetabolite that interferes with DNA synthesis. Preclinical studies using human cancer cell line models have shown potential therapeutic synergy between these two drugs by showing the maximum cytolytic effect using sequential 5FU followed by topotecan. In the current study, 5FU was used at a fixed dose of 375 mg/m2 given intravenously for five consecutive days on a 28 day cycle. Topotecan was dose-escalated in cohorts of patients from 0.5 to 1.0 mg/m2 given intravenously for 5 days after the 5FU dose. Eleven patients were entered at different dose levels. Both hematological and gastrointestinal toxicity were dose limiting. Diarrhea was the dose-limiting toxicity at the dose of 0.75 mg/m2 of topotecan. Two cases of grade 4 neutropenia were also observed at this dose level. One patient with small cell lung cancer had a complete response, while one patient with metastatic colorectal cancer had a partial remission. Three other patients had stable disease, lasting between 6 and 8 months. Overall, the regimen was well tolerated. A phase II study using a dose of 5FU at 375 mg/m2 followed by topotecan at 0.75 mg/m2 intravenously over 5 days every 28 days is recommended.
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PMID:Phase I study of sequential administration of topotecan and 5-fluorouracil in patients with advanced malignancies. 1219 19

We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50 mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min, intravenously on days 1, 8, 15). All patients were assessable for toxicity and survival; 28 patients were assessable for response. There were nine partial responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median time to progression was 3.5 months. Median survival time was 6.1 months. Major toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed in 7%. There was one treatment-related death due to febrile neutropenia and sepsis. This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer.
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PMID:Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer. 1223 2

Although recombinant human interleukin-3 (rhIL-3) shortens both the duration of chemotherapy-induced neutropenia and thrombocytopenia, its effect on nadir counts is limited. Concurrent administration of rhIL-3 and chemotherapy may enhance this effect. However, simultaneous administration of other hematopoietic growth factors and chemotherapy has resulted in enhanced myelosuppression. We investigated whether concomitant administration of rhIL-3 and chemotherapy would result in enhanced myelosuppression. Twelve patients with relapsed small cell lung cancer received vincristine, ifosfamide, mesna, and carboplatin on day 1 every four weeks. RhIL-3 was administered subcutaneously on days 1-14 during cycle 1 at doses of 4 (three patients) or 8 micrograms/kg/day (nine patients). During cycle 2 patients received only chemotherapy. No significant difference in leukocyte (1.4 +/- 1.0 vs. 0.9 +/- 0.4 x 10(9)/l (mean +/- SD), neutrophil (0.5 +/- 0.6 vs. 0.2 +/- 0.2 x 10(9)/l), and platelet (64 +/- 60 vs. 38 +/- 58 x 10(9)/l) nadir counts were demonstrated. The hemoglobin nadir level was significantly higher during cycle 1 (6.5 +/- 1.1 vs. 5.5 +/- 0.9 mmol/l, P = 0.05). Both leukocyte and platelet recovery were significantly enhanced in the rhIL-3 cycle. There was no significant difference in chemotherapy postponement or platelet transfusions. As a result of severe headaches, rhIL-3 administration was discontinued in one patient at 8 micrograms. RhIL-3 during this chemotherapy regimen for relapsed small cell lung cancer did not enhance myelotoxicity but did improve bone marrow recovery. This observation may increase the application of rhIL-3, for instance in combination with other hematopoietic growth factors.
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PMID:Recombinant human interleukin-3 administered concomitantly with chemotherapy in patients with relapsed small cell lung cancer. 1241 20

Extensive-stage small cell lung cancer (SCLC) is an aggressive disease with a median survival of approximately 8 months. Although current combination chemotherapy regimens provide high initial tumor response rates, they have not translated into large gains in survival. Topotecan and paclitaxel have nonoverlapping mechanisms of action and are active agents in SCLC. Additionally, these two agents demonstrate in vitro synergy in animal and human tumor models. We investigated the maximum tolerated dose of 3-day topotecan in combination with paclitaxel in previously untreated patients with extensive SCLC. Seventeen patients were enrolled in an open-label, phase I, dose-escalation study and were treated with intravenous paclitaxel 135-175 mg/m(2) over 1 hour on day 1, followed by intravenous topotecan 1.25-1.5 mg/m(2) over 30 minutes on days 1-3 of a 21-day course. Sixty-nine courses of therapy were administered with no delays due to hematologic toxicity. Prophylactic hematologic support was required for 24% of patients. The topotecan/paclitaxel combination was well tolerated, with 24%, 12%, and 6% of patients experiencing grade 3/4 neutropenia, anemia, or thrombocytopenia, respectively. Dose-limiting neutropenia was seen in three of five patients treated with topotecan 1.5 mg/m(2) and paclitaxel 175 mg/m(2). Therefore, topotecan 1.5 mg/m(2) with paclitaxel 135 mg/m(2) was determined to be the maximum tolerated dose. Of the 17 evaluable patients, 53% achieved a partial response and 18% achieved stable disease. In summary, we have identified a regimen of topotecan 1.5 mg/m(2) and paclitaxel 135 mg/m(2) that was well tolerated and active in this patient group. Additional studies of topotecan and paclitaxel at these dose levels are needed to fully elucidate the efficacy of this combination in extensive SCLC.
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PMID:Phase I study of paclitaxel and topotecan for the first-line treatment of extensive-stage small cell lung cancer. 1260 34


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