Biomedical subjects

KyungMann Kim

Publications and source records attributed to KyungMann Kim.

4 recordsLinked to original sources

PubMed2004

Admissible two-stage designs for phase II cancer clinical trials.

In a typical two-stage design for a phase II cancer clinical trial for efficacy screening of cytotoxic agents, a fixed number of patients are initially enrolled and treated. The trial may be terminated for lack of efficacy if the observed number of tumour responses after the first stage is too small, thus avoiding treatment of patient with inefficacious regimen. Otherwise, an additional fixed number of patients are enrolled and treated to accumulate additional information on efficacy as well as safety. The minimax and the so-called 'optimal' designs by Simon have been widely used, and other designs have largely been ignored in the past for such two-stage cancer clinical trials. Recently Jung et al. proposed a graphical method to search for compromise designs with features more favourable than either the minimax or the optimal design. In this paper, we develop a family of two-stage designs that are admissible according to a Bayesian decision-theoretic criterion based on an ethically justifiable loss function. We show that the admissible designs include as special cases the Simon's minimax and the optimal designs as well as the compromise designs introduced by Jung et al. We also present a Java program to search for admissible designs that are compromises between the minimax and the optimal designs.

Bayes Theorem↗

PubMed2004

A Phase II trial of flavopiridol (NSC #649890) in patients with previously untreated metastatic androgen-independent prostate cancer.

PURPOSE: Flavopiridol is a cyclin-dependent kinase inhibitor with preclinical activity against prostate cancer cell lines. A Phase II trial was conducted to determine the activity of flavopiridol in patients with metastatic hormone-refractory prostate cancer. EXPERIMENTAL DESIGN: A total of 36 patients was enrolled from several institutions and treated with a 72-h continuous infusion of flavopiridol every 14 days at the eventual starting dose of 40 mg/m(2)/day. Dose escalation up to 60 mg/m(2)/day was permitted if no significant toxicity was observed. Responses were assessed every 12 weeks. Only those patients completing four courses of the 72-h infusion were considered evaluable for response because the primary objective was to determine progression-free survival at 6 months given the cytostatic nature of the agent. RESULTS: This study was conducted in a two-stage fashion. During the first stage, at least 20 evaluable patients needed to be enrolled to assess response. There were 22 of 36 patients evaluable for response. No objective responses were observed. Only 4 patients had stable disease for 16, 26, 29, and 48 weeks, respectively, stopping the trial by design as only 3 of 22 (14%) of the patients met the 6-month progression-free survival end point. The most common toxicities were diarrhea (grade 1 and 2) and nausea, although some grade 3 and 4 diarrhea (11 and 6%, respectively) were evident. CONCLUSIONS: Flavopiridol has disappointing single-agent activity in hormone-refractory prostate cancer when administered at this dose and schedule. Its use in prostate cancer should be reserved for evaluation in combination therapies or alternative schedules.

Aged↗

PubMed2003

Phase II study of second-line gemcitabine in sensitive or refractory small cell lung cancer.

UNLABELLED: Small cell lung cancer (SCLC) is highly sensitive to chemotherapy. Despite a dramatic initial response, however, most patients relapse. Given the activity of gemcitabine in non-small cell lung cancer (NSCLC), and early clinical trials suggesting activity of gemcitabine in chemo-naive SCLC patients, we conducted a phase II study to determine the efficacy and toxicities of gemcitabine in SCLC patients who have failed first-line chemotherapy. Gemcitabine 1250 mg/m(2) was given intravenously on days 1 and 8, every 3 weeks. Eligibility criteria included prior treatment with only one chemotherapy regimen and Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients with brain metastases were eligible. RESULTS: Between April 1998 and October 2001, 27 patients were enrolled: 15 patients with sensitive (S) disease (recurred>3 months after first-line chemotherapy) and 12 patients with refractory (R) disease (failed<3 months after first-line chemotherapy). Median age was 61 (range 45-74). All patients had received prior platinum-based therapy involving etoposide and either cisplatin or carboplatin. There were one early death and two early withdrawals because of toxicity. No responses were observed. Of 24 patients who received at least two cycles of gemcitabine, only three achieved stable disease after six cycles while 21 progressed. The median time to progression (TTP) was 6 weeks in S group, 5.6 weeks in R group, and 6 weeks overall. After a minimum potential follow-up of almost 1 year for all patients, the median survival was 8.8 months in S group, 4.2 months in R group, and 6.4 months for the whole group. One-year survival rate was 33.3% in S group, 16.7% in R group, and 25.4% for all patients. Myelosuppression was the most commonly observed adverse effect, with grade 3/4 neutropenia in 30%, and grade 3 thrombocytopenia in 30%. One patient (3.7%) developed neutropenic fever. Respiratory failure and death, possibly related to pulmonary toxicity, was observed in one patient (3.7%). CONCLUSION: monotherapy gemcitabine as second-line agent has limited activity in previously treated SCLC.

Aged↗

PubMed2002

Group sequential methods for an ordinal logistic random-effects model under misspecification.

Interim analyses in clinical trials are planned for ethical as well as economic reasons. General results have been published in the literature that allow the use of standard group sequential methodology if one uses an efficient test statistic, e.g., when Wald-type statistics are used in random-effects models for ordinal longitudinal data. These models often assume that the random effects are normally distributed. However, this is not always the case. We will show that, when the random-effects distribution is misspecified in ordinal regression models, the joint distribution of the test statistics over the different interim analyses is still a multivariate normal distribution, but a sandwich-type correction to the covariance matrix is needed in order to obtain the correct covariance matrix. The independent increment structure is also investigated. A bias in estimation will occur due to the misspecification. However, we will also show that the treatment effect estimate will be unbiased under the null hypothesis, thus maintaining the type I error. Extensive simulations based on a toenail dermatophyte onychomycosis trial are used to illustrate our results.

Biometry↗