Pooled analysis of S-1 trials in non-small cell lung cancer according to histological type.

Background: The antimetabolic agent S-1 inhibits thymidylate synthase similar to pemetrexed, but through a different mechanism of action. Whether the antitumour activity of S-1 depends on histological type remains unclear. We analysed pooled data from 2 phase II clinical studies of cisplatin and S-1 in patients with previously untreated advanced non-small cell lung cancer.

Phase I/II study of docetaxel and S-1, an oral fluorinated pyrimidine, for untreated advanced non-small cell lung cancer.

The purpose of this phase I/II study is to evaluate a new combination chemotherapy consisting of docetaxel and S-1 as front-line therapy for patients with untreated advanced non-small cell lung cancer (NSCLC). The treatment included docetaxel on day 1 and oral S-1 at a fixed dose of 40mg/m(2) administered twice daily on days 1-14 and repeated every 3 weeks. In phase I, docetaxel at escalating doses of 40 (level 0), 50 (level 1) and 60mg/m(2) (level 2) was administered starting from level 1.

Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, given weekly to advanced solid tumor patients for 3 weeks.

TZT-1027 is a novel synthetic dolastatin 10 derivative that inhibits tubulin polymerization. A phase I study was conducted to determine the maximum tolerated dose (MTD) of TZT-1027, and to assess its pharmacokinetic profile in Japanese patients with advanced solid tumors following administration of the drug weekly for 3 weeks. Eligible patients had advanced solid tumors that failed to respond to standard therapy or for which no standard therapy was available, and met the following criteria: performance status ≤2 and acceptable organ function.

Docetaxel in combination with either cisplatin or gemcitabine in unresectable non-small cell lung carcinoma: a randomized phase II study by the Japan Lung Cancer Cooperative Clinical Study Group.

Purpose: To evaluate whether cisplatin-free chemotherapy (docetaxel and gemcitabine [DG]) provides a comparable alternative to cisplatin-based chemotherapy (docetaxel and cisplatin [DC]) as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC).

Patients And Methods: Patients (n = 133) with stage IIIB to IV NSCLC were randomly assigned to receive DG (docetaxel 60 mg/m, day 8 + gemcitabine 800 mg/m, days 1 and 8, every 3 weeks; n = 65) or DC (docetaxel 60 mg/m, day 1 + cisplatin 80 mg/m, day 1, every 3 weeks; n = 68). The primary end point of the study was overall response rate.

[Late phase II clinical study of KW-2307 in advanced/recurrent breast cancer patients (II)].

A late phase II clinical study (II) of a novel vinca alkaloid derivative KW-2307 (vinorelbine ditartrate) in advanced/recurrent breast cancer patients was performed at 22 institutions throughout Japan. An intravenous dose of KW-2307, 20 mg/m2, was administered once a week. Of the 60 patients enrolled in the study, 58 were eligible and 56 were evaluable.

S-1 plus cisplatin combination chemotherapy in patients with advanced non-small cell lung cancer: a multi-institutional phase II trial.

Purpose: To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients.

Experimental Design: In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m(2) twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. This schedule was repeated every 5 weeks.

Uracil/tegafur plus cisplatin with concurrent radiotherapy for locally advanced non-small-cell lung cancer: a multi-institutional phase II trial.

Purpose: To evaluate the efficacy and toxicity of a novel combination treatment using concurrent radiotherapy with cisplatin plus UFT, which is comprised of uracil and tegafur, in locally advanced non-small cell lung cancer (NSCLC) patients.

Experimental Design: In this Phase II trial, patients with unresectable stage III NSCLC were treated with the oral administration of UFT (400 mg/m(2)/d tegafur) on days 1-14 and days 29-42 whereas 80 mg/m(2) cisplatin was administered i.v.

Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group.

Purpose: Few randomized trials have demonstrated survival benefit of combination chemotherapy involving new agents plus cisplatin compared with classic combination chemotherapy in advanced non-small-cell lung cancer (NSCLC). The primary aim of this study was to test whether docetaxel plus cisplatin (DC) improves survival compared with vindesine plus cisplatin (VdsC) in patients with previously untreated stage IV NSCLC.

Patients And Methods: Eligible, stage IV, chemotherapy-naive patients (n = 311) were randomly assigned to receive docetaxel 60 mg/m(2) intravenously on day 1 plus cisplatin 80 mg/m(2) intravenously on day 1 of a 3- or 4-week cycle, or vindesine 3 mg/m(2) intravenously on days 1, 8, and 15 plus cisplatin 80 mg/m(2) intravenously on day 1 of a 4-week cycle.

A phase II study of topotecan in patients with relapsed small-cell lung cancer.

An early phase II study of topotecan produced favorable results in a small number of untreated and previously treated patients with small-cell lung cancer (SCLC). This multicenter study was conducted in patients with relapsed SCLC at 19 medical institutions in Japan. Topotecan 1.

Individually different "weights" of quality of life assessment in patients with advanced nonsmall-cell lung cancer.

Background And Objective: The structure of quality of life (QOL) assessment was investigated by estimating subject-specific as well as population-averaged "weights" for four domains (functional, physical, mental, and psychosocial) relative to global QOL.

Methods: Among 583 eligible patients with advanced nonsmall-cell lung cancer in two phase III trials, 377 completed QOL questionnaires at baseline, and during treatment. A random coefficients model was applied, using the global QOL score and scores for the four domains as response and explanatory variables, respectively.

Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer.

To determine a standard combination chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), we conducted a phase III trial of irinotecan (CPT-11) to test the hypotheses that CPT-11+cisplatin is superior to cisplatin+vindesine and that CPT-11 monotherapy is not inferior to cisplatin+vindesine. A total of 398 patients with previously untreated NSCLC were randomised to receive cisplatin+CPT-11 (CPT-P), cisplatin+vindesine (VDS-P) or CPT-11 alone (CPT). In the CPT-P arm, CPT-11 60 mg m(-2) was administered on days 1, 8 and 15, and cisplatin 80 mg m(-2) was administered on day 1.

The quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD): validity and reliability in japanese patients with advanced non-small-cell lung cancer.

The quality of life questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), which consists of four domains (functional, physical, mental, and psychosocial) and a global face scale, was developed as a generic questionnaire for Japanese cancer patients undergoing chemotherapy. We examined the validity and reliability of this questionnaire in Japanese patients with advanced non-small-cell lung cancer (NSCLC), who participated in two randomized phase III trials. After excluding two items, one showing low test-retest reliability and the other showing poor convergent validity for the target population, Cronbach's alpha coefficients ranged from 0.

Phase I studies of nogitecan hydrochloride for Japanese.

Background: SmithKline Beecham synthesized camptothecin analogs and identified nogitecan hydrochloride (topotecan) with a broad spectrum of antitumor activity and less toxicity than camptothecin. Because preclinical and overseas clinical data indicated the antitumor effect of nogitecan hydrochloride with a 5-day repeat-dose schedule, we carried out phase I studies in Japan to determine the maximum tolerated dose (MTD), pharmacokinetics, and antitumor effect of nogitecan hydrochloride.

Methods: Phase I studies of nogitecan hydrochloride given by single and 5-day repeat dosing were carried out in patients with various solid tumors at 15 medical institutions in Japan.

A study of the combination of gemcitabine hydrochloride (LY188011) and cisplatin in non-small-cell lung cancer: 3-week schedule.

Background: It has been reported that the combination of gemcitabine (LY188011; GEM) and cisplatin (CDDP) in a 4-week schedule showed a high response rate for patients with non-small-cell lung cancer (NSCLC), but GEM could not be administered on day 15 because of increased myelosuppression in many patients. The present study was performed to evaluate the efficacy and safety of GEM and CDDP in a 3-week schedule.

Methods: Patients with unresectable NSCLC without prior chemotherapy were enrolled.

Early phase II study of S-1, a new oral fluoropyrimidine, for advanced non-small-cell lung cancer.

Background: The efficacy and safety of S-1, a new oral fluoropyrimidine, were evaluated in patients with non-small-cell lung cancer (NSCLC). The objective of this study was to determine whether the drug should be investigated in a late phase II study.

Methods: Each treatment course consisted of an oral dose of S-1, 50 mg/body or 75 mg/body, twice a day for 28 days followed by a 2-week washout period.

Phase II study of S-1, a novel oral fluorouracil, in advanced non-small-cell lung cancer.

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety.

Phase I and pharmacologic study of docetaxel and irinotecan in advanced non-small-cell lung cancer.

Purpose: We conducted a phase I trial of docetaxel, a new antimicrotubule agent, combined with irinotecan (CPT-11), a topoisomerase I inhibitor. The aim was to determine the maximum-tolerated dose (MTD) of docetaxel combined with CPT-11, as well as the dose-limiting toxicities (DLTs) of this combination in advanced non-small-cell lung cancer (NSCLC) patients.

Patients And Methods: Thirty-two patients with stage IIIB or IV NSCLC were treated at 4-week intervals with docetaxel (60 minutes, day 2) plus CPT-11 (90 minutes, days 1, 8, and 15).

[A phase II study of irinotecan combined with cisplatin in non-small cell lung cancer. CPT-11 Lung Cancer Study Group].

Based upon the results of phase I study of irinotecan (CPT-11) combined with cisplatin (CDDP) on non-small cell lung cancer (NSCLC), a combination phase II study on NSCLC was carried out from Feb., 1992 to Sep., 1992.

UFT plus cisplatin combination chemotherapy in the treatment of patients with advanced nonsmall cell lung carcinoma: a multiinstitutional phase II trial. For the Japan UFT Lung Cancer Study Group.

Background: Combination chemotherapy comprised of oral UFT (a combination of tegafur and uracil) and cisplatin was shown to be an effective regimen for the treatment of advanced nonsmall cell lung carcinoma and to be associated with a low incidence rate of toxicity in a previous, single institution, Phase II trial on a small patient sample. Therefore, the current multiinstitutional Phase II trial was conducted to confirm the earlier results.

Methods: Eligible patients had histologically or cytologically confirmed Stage IIIB or IV nonsmall cell lung carcinoma and good performance status.

[Navelbine (vinorelbine): a review of its antitumor activity and toxicity in clinical studies].

Navelbine is a derivative of vinca alkaloid that interferes with tubulin assembly and exhibits antitumor activity. Clinical trials with single-agent Navelbine proved it to be effective against non-small cell lung cancer (NSCLC), breast cancer, and other tumors. At present, clinical trials by combination with various drugs are ongoing NSCLC and breast cancer.

Effects of anti-emetic drug (tropisetron) on quality of life during chemotherapy: use of a diary-type questionnaire and application of summary measures for assessment in a randomized, multicentre study. Joint Research Group for Tropisetron Double-Blind Comparative Study.

The role of tropisetron as an anti-emetic drug in the prevention of delayed nausea and vomiting remains unclear. Therefore, effectiveness of tropisetron in patients receiving cancer chemotherapy was evaluated by application of summary measures using a quality of life (QOL) questionnaire. The diary-type QOL self-rating questionnaire was constituted by seven scales.

[Short history of the clinical developments in lung cancer treatment].

Through the 1980's and the early part of the 1990's several new anti-cancer drugs to fight lung cancer were clinically introduced, bringing cytotoxic chemotherapy to play an important role as a mainstay in the combined modality therapy for both small cell and non-small cell lung cancer. This is different from the state prior to the introduction of these drugs. There is no need to say that these advances were supported by the unceasing efforts of oncologists and their patience in performing the many randomized controlled trials.

[Phase I study of gemcitabine hydrochloride (LY 188011) combination therapy with cisplatin in the patients with non-small cell lung cancer].

The combination Phase I study of gemcitabine hydrochloride with cisplatin was conducted in the patients with non-small cell lung cancer (NSCLC) at 5 investigation sites. Gemcitabine was administrated on day 1, 8 and 15 and cisplatin on day 1 of each 28-day cycle. The dosage of cisplatin was fixed to 80 mg/m2 and the dosage of Gemcitabine was gradually escalated in 3 dosing level from 600, 800 to 1,000 mg/m2.

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.

[Early phase II trial of oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer. ETP 21 Study Group--Cervical-Ovarian Cancer Group].

We conducted multi-site early phase II trial or oral etoposide administered for 21 consecutive days in patients with cervical or ovarian cancer in cooperation with 19 institutes. Fifty mg/body of oral etoposide was administered daily for 21 consecutive days. Cycles were repeated every 28 days.