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Biomedical subjects

David H Johnson

Publications and source records attributed to David H Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2004

Docetaxel for malignant mesothelioma: phase II study of the Eastern Cooperative Oncology Group.

This Eastern Cooperative Oncology Group phase II trial was conducted to study the effectiveness of docetaxel in patients with malignant mesothelioma. Patients were treated with docetaxel 100 mg/m2 intravenously administered as a 1-hour infusion repeated every 3 weeks. The study accrued a total of 20 patients, 1 of whom was considered ineligible. Of the 19 eligible patients, 1 patient (5%) achieved a partial response, 3 patients (16%) had stable disease, 11 patients (58%) had progressive disease, and 4 patients (21%) were unevaluable. The study was terminated after the first accrual stage because of an insufficient number of complete or partial responses. To date, only 1 patient (with stable disease) has not relapsed. The estimated median survival time is 4 months and the estimated median time to treatment failure is 2.2 months. There were 3 early deaths associated with the treatment regimen: severe gastrointestinal toxicity, hemorrhage, and an acute pulmonary event. Docetaxel as a single agent does not demonstrate evidence of activity in malignant mesothelioma.

Aged↗
PubMed2003

Pilot trial of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib plus carboplatin and paclitaxel in patients with stage IIIB or IV non-small-cell lung cancer.

PURPOSE: Gefitinib is an oral agent that inhibits the tyrosine kinase of the epidermal growth factor receptor. In phase I trials gefitinib was well tolerated and antitumor activity was seen in pretreated non-small-cell lung cancer (NSCLC) patients. Preclinical studies indicated enhanced effects when gefitnib was added to carboplatin or paclitaxel. This pilot trial combined gefitinib with carboplatin and paclitaxel to define the toxicities of the combination and assess drug-drug interactions in untreated advanced NSCLC patients. PATIENTS AND METHODS: Initially (part 1) patients were randomly assigned to receive intermittent gefitinib with cycle 1 or 2 of chemotherapy. Thereafter (part 2), the highest dose of gefitinib that was given without dose-limiting toxicity (DLT) from part 1 was administered continuously beginning with the first cycle of chemotherapy. Three sequentially enrolled cohorts received gefitinib 250 and 500 mg (intermittently) and 500 mg (continuously). RESULTS: We treated 24 patients; nine patients with 250 mg and 15 patients with 500 mg (nine patients continuous). Two occurrences of DLT were observed. One patient (500 mg, part 1) developed grade 3 rash and another patient (part 2) developed prolonged neutropenia. Steady-state gefitinib levels did not affect exposure to chemotherapy. In a limited sample, chemotherapy modestly increased the gefitinib area under concentration-time curve at steady-state and minimum steady-state trough concentration. Partial responses were observed in five of 24 patients. The median survival was 8 months. CONCLUSION: The gefitinib with carboplatin and paclitaxel regimen was generally well tolerated and no unanticipated toxicities or clinically relevant pharmacokinetic interactions were observed. Both doses of gefitinib were believed to be safe for further study with chemotherapy. This regimen was thus tested in a completed randomized phase III trial.

Adult↗
PubMed2003

Early change in patient-reported health during lung cancer chemotherapy predicts clinical outcomes beyond those predicted by baseline report: results from Eastern Cooperative Oncology Group Study 5592.

PURPOSE: To determine the ability of longitudinal patient-reported health (PRH) scores to enhance prediction of clinical outcomes beyond baseline scores. PATIENTS AND METHODS: In 573 advanced non-small-cell lung cancer patients enrolled in a phase III clinical trial, we used baseline and 6-week follow-up PRH scores to predict best response to treatment, disease progression, and survival. Using regression analyses, we tested the predictive ability of the five subscales of the Functional Assessment of Cancer Therapy-Lung (physical, functional, social/family, emotional well-being, and the lung cancer subscale) as well as the trial outcome index (TOI) aggregate score. RESULTS: After clinical factors were controlled for, baseline physical well-being (PWB) and TOI scores predicted all three clinical outcomes. A higher baseline PWB score was associated with a better response to treatment (odds ratio, 1.09; P <.001) and lower risk of death (risk ratio, 0.95; P <.001). Higher baseline TOI score was associated with a lower risk of disease progression (risk ratio, 0.98; P <.001). These two baseline predictors (PWB and TOI) were then used along with 6-week change scores to classify patients into four groups: low baseline-declined, low baseline-improved, high baseline-declined, and high baseline-improved. Patients with low baseline-declined PWB scores showed the worst responses to treatment and survived the shortest duration. Patients with low baseline-declined TOI scores had the shortest time to progression. CONCLUSION: The physical aspects of baseline PRH and PRH change during chemotherapy are significant predictors of clinical outcomes in lung cancer. This has implications for patient stratification in clinical trials and may aid decision-making in clinical practice.

Adult↗
PubMed2003

Factors associated with death among adults <55 years of age hospitalized for community-acquired pneumonia.

An administrative database was used to study death occurring among adults aged 18-55 years who were hospitalized during the period from 1 April 1994 through 31 March 1999 for treatment of community-acquired pneumonia. In-hospital case-fatality rates for the first 10 days of hospitalization and overall were 2.1% and 3.2%, respectively, for 11,684 patient hospitalizations. Patient factors (age, sex, and comorbidity) were the most important associations with death. Aspiration provided the largest explanation of variance in deaths occurring during the first 10 days of hospitalization (odds ratio, 5.0; 95% confidence interval, 3.7-6.8). Busy hospitals (higher occupancy and higher number of daily admissions) were not associated with higher case-fatality rates. Bigger hospitals (metropolitan hospitals) had higher case-fatality rates, but this was more likely related to greater comorbidity and severity of pneumonia. Death due to community-acquired pneumonia among young and middle-aged adults is infrequent and is more related to the severity of pneumonia and to such risk factors as aspiration than to the manner in which the provision of care is organized.

Adolescent↗
PubMed2003

Targeted therapy in non-small cell lung cancer: myth or reality.

In oncology, the term 'targeted therapy' is used to describe drugs that target only the cancer cells and spare normal cells thereby reducing host toxicity while simultaneously increasing the eradication of cancer. Trastuzumab and imatinib are well known examples of successful targeted therapy. Newer agents like gefitinib and cetuximab offer hope that targeted therapy also may yield therapeutic benefit for such refractory malignancies as lung and colon cancers. One of many remaining challenges is to identify markers, molecular or clinical, that predict for responsiveness to a specific targeted therapy (e.g. HER2/neu positivity and trastuzumab responsiveness). However, using emerging technologies such as gene or protein profiling, it may be possible to predict a tumor's responsiveness to a particular targeted therapy based on its molecular signature. If true, clinicians might then possess the ability to predict a tumor's clinical behavior and shape its density through specific, targeted interventions.

Antineoplastic Agents↗
PubMed2003

Gefitinib (Iressa) trials in non-small cell lung cancer.

Gefitinib (Iressa) is a synthetic anilinoquinazoline capable of inhibiting the epidermal growth factor receptor tyrosine kinase in vitro at nanomolar concentrations. In phase I trials, gefitinib was well tolerated at doses above that required to induce antitumor effects in vitro. Notably, antitumor activity was observed in lung cancer patients. These findings resulted in the initiation of phase II trials employing gefitinib monotherapy in patients with recurrent non-small cell lung cancer (the so-called IDEAL trials). Study participants were randomized to 250 mg or 500 mg of gefitinib per day. Objective response rates between 10 and 20% were achieved with minimal host related toxicity (mainly acne like rash and mild diarrhea). Median survivals ranged between 6 and 8 months. Subsequently, phase III trials (the so-called INTACT trials) combined gefitinib and chemotherapy in chemonaive patients with advanced non-small cell lung cancer. These trials failed to demonstrate a survival advantage with the addition of gefitinib to standard platinum-based chemotherapy regimens. However, overall host related toxicities were not substantially worsened with the addition of gefitinib to chemotherapy. Further studies employing single agent gefitinib as well as regimens employing a different sequencing of chemotherapy and gefitinib are planned in recurrent and previously untreated lung cancer patients.

Aged↗
PubMed2003

Second primary tumors following adjuvant therapy of resected stages II and IIIa non-small cell lung cancer.

The occurrence of second primary tumors (SPTs) following adjuvant therapy for resected stages II and IIIa non-small cell lung cancer (NSCLC) was investigated. Data regarding SPTs were prospectively collected in all patients accrued to Eastern Cooperative Group Oncology E3590 (a phase III trial of adjuvant therapy in patients with completely resected stages II and IIIa NSCLC). Four hundred eighty-eight patients were accrued to the study, 242 to the RT arm and 246 to the CRT arm. Median follow-up was 73 months. Thirty patients (6.1%) developed 33 SPTs, 20 in the RT arm and ten in the CRT arm. Ten SPTs occurred within the upper aerodigestive tract, six in the RT arm and four in the CRT arm. Twenty-three SPTs occurred in other organs, 17 in the RT arm and six in the CRT arm. Median time to detection of a SPT for those patients randomized to RT and CRT was 43 and 36 months, respectively. The incidence of SPTs was 1.8% per patient-year of follow-up. Excluding skin tumors, the relative risk of death following diagnosis of a SPT for patients randomized to the CRT arm as compared with those randomized to RT alone was 2.26 (95% confidence interval, 0.78-5.58, P=0.12). Patients are at risk for developing a SPT following resection of stages II and IIIa NSCLC. The majority of SPTs occur outside the aerodigestive tract. Following development of a non-skin SPT, the survival difference between patients who had received adjuvant CRT and those treated with adjuvant RT alone was not significant.

Adult↗
PubMed2003

Improving the evaluation of new cancer treatments: challenges and opportunities.

There are, at present, ten times more anticancer drugs being tested in clinical trials than there were 15 years ago. Many of the new classes of agents, however, are predicted to work in only small subpopulations of patients, target unconventional aspects of tumour development and interact with other agents in an unpredictable manner. How can clinical trials be re-designed to accommodate the new features of targeted anticancer drugs?

Antineoplastic Agents↗
PubMed2003

The effects of community-acquired pneumonia during pregnancy ending with a live birth.

OBJECTIVE: The incidence and outcomes for community-acquired pneumonia during a pregnancy ending with a live birth in the province of Alberta, Canada, were analyzed. STUDY DESIGN: Hospital abstracts and vital statistics data between April 1, 1994, to March 31, 1999, were used. RESULTS: The incidence of hospitalization for community-acquired pneumonia was 1.51 (95% CI 1.35-1.67) per 1000 pregnancies in mothers 18 years and older compared with 1.47 (95% CI 1.42-1.51) per 1000 women (18 to 49 years) in the general population. The relative risk of staying longer at hospital for pneumonia was 0.44 during pregnancy compared with nonpregnant mothers with pneumonia. The relative risk of staying longer at hospital during delivery was 1.88, higher in those with a past hospitalization for community-acquired pneumonia. The relative risk of a small-for-gestational-age newborn infant was 1.86 for those with a past hospitalization for community-acquired pneumonia compared with those without a past hospitalization. CONCLUSION: Community-acquired pneumonia during most pregnancies ending with a live birth appears to be well tolerated by mothers and newborn infants.

Adult↗
PubMed2002

Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America.

BACKGROUND: To determine the changes in clinical trials and outcomes of patients with limited-stage small cell lung carcinoma (SCLC) treated on Phase III randomized trials initiated in North America between 1972 and 1992. METHODS: Phase III trials from 1972 to 1992 for patients with limited-stage SCLC were identified. Patients with limited-stage SCLC treated during a similar time interval were also evaluated in the Surveillance, Epidemiology, and End Results (SEER) database. Trends were tested in the number of trials, in the number and gender of patients entered on trial, and in survival duration over time. RESULTS: Thirty trials involving 6564 patients were eligible for analyses. Nineteen trials (61%) involving 3626 patients were initiated within the first half of this time period (1972-1981). The median of median survival times of all patients treated on the control arms of the Phase III trials initiated between 1972 and 1981 and between 1982 and 1992 were 12.0 months (range, 10-16 months) and 17.0 months (range, 11-20 months), respectively (P < 0.001). Of 26 studies available for survival analysis, 5 (19%) showed a statistically significant survival prolongation in the experimental arm compared with the control arm with a median prolongation of 3.4 months (range, 1-5.2 months). All five evaluated some aspect of thoracic radiation therapy. Over a similar time period, there was a 6.4-month increase in the median survival of limited-stage SCLC patients listed in the SEER database (P < 0.0001) and a more than doubling of the 5-year survival from 5.2% to 12.1% (P = 0.0001). CONCLUSIONS: Analyses of the patients with limited-stage SCLC treated on Phase III trials in North America initiated between 1972 and 1992 and those listed in the SEER database show significant improvements in median survivals. Furthermore, the 5-year survival of patients with limited-stage SCLC listed in the SEER database has more than doubled over the last 25 years. Further research will be needed to determine the relative contribution of improved therapy, supportive care, and stage migration to this prolongation in survival.

Adult↗
PubMed2002

Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial.

BACKGROUND: Older patients, even if fit, are often considered incapable of tolerating platinum-based systemic therapy. We performed a retrospective analysis of Eastern Cooperative Oncology Group (ECOG) 5592, a phase III randomized trial of platinum-based chemotherapy regimens for non-small-cell lung cancer (NSCLC), and compared outcomes in enrollees 70 years of age and older with those in younger patients. METHODS: ECOG carried out a randomized phase III trial of cisplatin plus either etoposide or paclitaxel in chemotherapy-naïve NSCLC patients with stages III(B) or IV disease. Toxic effects, response rates, and survival rates were compared between age groups. All P values were two-sided. RESULTS: A total of 574 patients enrolled from August 1993 through December 1994 were evaluable. Eighty-six (15%) were 70 years old or older. Older patients had a higher incidence of cardiovascular (P =.009) and respiratory (P =.04) comorbidities and nonanalgesic medication use (P =.02). Leukopenia (P<.001) and neuropsychiatric toxicity (P =.002) were more common in elderly men than in younger men. Elderly women lost more weight than younger women (P =.006). Other toxic effects were similar in older and younger patients. The proportions with clinical partial or complete response (21.5% versus 23.3%; Fisher's exact test, P =.66), median time to progression (4.37 versus 4.30 months; log-rank test, P =.29), and survival distribution (log-rank test, P =.29; median survival, 9.05 versus 8.53 months; 1-year survival, 38% versus 29%; and 2-year survival, 14% versus 12%) were similar in patients younger than 70 years and 70 years old or older. Baseline quality-of-life and treatment-outcome indices were similar. Equivalent declines over time in functional well-being occurred in both groups. CONCLUSION: Response rate, toxicity, and survival in fit, elderly NSCLC patients receiving platinum-based treatment appear to be similar to those in younger patients, although patients 70 years old or older have more comorbidities and can expect more leukopenia and neuropsychiatric toxicity. Advanced age alone should not preclude appropriate NSCLC treatment.

Aged↗
PubMed2002

Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.

BACKGROUND: We conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non-small-cell lung cancer. METHODS: A total of 1207 patients with advanced non-small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens: cisplatin and gemcitabine, cisplatin and docetaxel, or carboplatin and paclitaxel. RESULTS: The response rate for all 1155 eligible patients was 19 percent, with a median survival of 7.9 months (95 percent confidence interval, 7.3 to 8.5), a 1-year survival rate of 33 percent (95 percent confidence interval, 30 to 36 percent), and a 2-year survival rate of 11 percent (95 percent confidence interval, 8 to 12 percent). The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens. Treatment with cisplatin and gemcitabine was associated with a significantly longer time to the progression of disease than was treatment with cisplatin and paclitaxel but was more likely to cause grade 3, 4, or 5 renal toxicity (in 9 percent of patients, vs. 3 percent of those treated with cisplatin plus paclitaxel). Patients with a performance status of 2 had a significantly lower rate of survival than did those with a performance status of 0 or 1. CONCLUSIONS: None of four chemotherapy regimens offered a significant advantage over the others in the treatment of advanced non-small-cell lung cancer.

Adult↗
PubMed2002

What is a clinically meaningful change on the Functional Assessment of Cancer Therapy-Lung (FACT-L) Questionnaire? Results from Eastern Cooperative Oncology Group (ECOG) Study 5592.

To assess the impact of disease and treatment on patients with advanced non-small cell lung cancer (NSCLC), we set out to determine a clinically meaningful change (CMC) on the Lung Cancer Subscale (LCS) and the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy-Lung (FACT-L) questionnaire. We used data from Eastern Cooperative Oncology Group study 5592 (E5592), a randomized trial comparing three chemotherapeutic regimens in 599 advanced NSCLC patients. Patients completed the FACT-L at baseline (pretreatment), 6 weeks, 12 weeks, and 6 months. Comparing across baseline performance status (0 vs. 1), prior weight loss (<5% vs. > or = 5%), and primary disease symptoms (< or = 1 vs. >1), LCS and TOI score differences ranged from 2.4 to 3.6 and 6.5 to 9.2, respectively (all Ps <.001). Mean improvement in LCS score from baseline to 12 weeks was 2.4 points in patients who had responded to treatment versus 0.0 points in patients who had progressive disease. Twelve-week LCS change scores for patients progressing early were 3.1 points worse than those of patients progressing later (mean = -1.2 vs.1.9, respectively). Similarly, the average TOI change score from baseline to 12 weeks was -6.1 for patients who had progressive disease versus -0.8 points for patients who had responded to treatment. Twelve-week TOI change scores for patients progressing early (mean = -8.1) were 5.7 points worse than those of patients progressing later (mean = -8.1 vs. -2.4, respectively). Analyses assuming nonrandom missing data resulted in slightly larger differences. Clinically relevant change scores were estimated as two to three points for the LCS and five to seven points for the TOI, setting upper limits for minimal CMCs. These values were comparable to suggested distribution-based criteria of a minimally important difference. These results support use of a two to three point change in the LCS and five to six point change on the TOI of the FACT-L as a CMC, and offer practical direction for inclusion of important patient-based endpoints in lung cancer clinical trials.

Adult↗