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Biomedical subjects

J Q Su

Publications and source records attributed to J Q Su.

33 records · Page 2Linked to original sources
PubMed1994

Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung cancer: results of a North Central Cancer Treatment Group randomized clinical trial.

PURPOSE: The combination of etoposide (E) and cisplatin (P) is an accepted standard therapy for small-cell lung cancer (SCLC); however, the optimal sequencing and administration schedule has not been defined. This study was designed to evaluate different sequencing and administration schedules of E and P in the treatment of SCLC. PATIENTS AND METHODS: Five hundred fifty-two eligible patients with limited-(LD) and extensive-stage (ED) SCLC were randomized to receive one of the following regimens: arm A, P 30 mg/m2 by intravenous (IV) bolus followed by E 130 mg/m2 bolus; arm B, E 130 mg/m2 bolus followed by P 30 mg/m2 bolus; arm C, E 130 mg/m2 by 24-hour infusion and P 30 mg/m2 bolus at the end of each 24-hour infusion of E; arm D, E 130 mg/m2 by 24-hour infusion and P 45 mg/m2 by 24-hour infusion on day 2 and 3 only. Two 3-day induction cycles of IV EP were administered 4 weeks apart. Subsequent therapy was the same for all arms, consisting of four cycles of cyclophosphamide, doxorubicin, and vincristine (CAV) at 4-week intervals. Consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) were administered to responders. RESULTS: The overall response rate (84%) was similar in all treatment arms. Treatment arm A was associated with the best complete response (CR) rate (52%), the most favorable median survival time (MST) of 15 months, and a 26% 2-year survival rate. Patients with LD on arm A had a MST of 20 months and a 42% 2-year survival rate. Multivariate analysis indicated that extent of disease, performance status, arm of therapy, and sex were significant independent factors influencing survival. Toxicity of the four regimens was similar, except for greater thrombocytopenia on arm D. CONCLUSION: The bolus administration of EP with E following P for the first two cycles of chemotherapy was the most effective regimen, with especially encouraging survival for LD patients.

Actuarial Analysis↗
PubMed1994

Phase III trial of recombinant interferon gamma in complete responders with small-cell lung cancer.

PURPOSE: We evaluated the effect of recombinant interferon gamma (rIFN-gamma) on survival and toxicity in small-cell lung cancer (SCLC) patients in complete remission (CR). PATIENTS AND METHODS: One hundred patients in CR following treatment with six cycles of combination chemotherapy, thoracic radiotherapy (TRT), and prophylactic cranial irradiation (PCI) were studied. All patients had been enrolled onto a cooperative group trial (North Central Cancer Treatment Group [NCCTG] 86-20-51). Patients received observation only or rIFN-gamma at a dose of 4 x 10(6) U subcutaneously per day for 6 months. RESULTS: Six patients (12%) did not comply with rIFN-gamma treatment. Substantial nonhematologic toxicities consisting of chills, myalgia, lethargy, and alteration of mood-personality were observed. No patient experienced life-threatening or fatal toxicity. The median times to progression for rIFN-gamma treatment or observation were 6.9 and 8.1 months (P = .54). The median survival times were 13.3 and 18.8 months, respectively (P = .43). Approximately 70% of all patients relapsed within 2 years. CONCLUSION: Time to progression and survival were inferior in patients treated with rIFN-gamma compared with randomized control subjects, although this difference was not statistically significant. These data indicate that rIFN-gamma treatment is not associated with a 33% improvement in survival (P = .04). Because of the high rate of relapse, SCLC patients in CR are an ideal group in which to evaluate novel and minimally toxic agents.

Adult↗
PubMed1994

Prophylactic cranial irradiation in complete responders with small-cell lung cancer: analysis of the Mayo Clinic and North Central Cancer Treatment Group data bases.

PURPOSE: To determine whether prophylactic cranial irradiation (PCI) has an impact on brain failure and survival in patients with small-cell lung cancer (SCLC) who have achieved a complete response to chemotherapy with or without thoracic radiation therapy (TRT). METHODS: Between 1975 and 1990, the Mayo Clinic and North Central Cancer Treatment Group entered 1,617 patients on 15 phase II and III SCLC protocols of chemotherapy with or without TRT and PCI. RESULTS: Of 772 patients with limited disease, 457 (59%) achieved a complete response, compared with 200 of 845 patients (24%) with extensive disease. With follow-up durations of 2 to 17 years (median, 4), the median survival time and 2-, 5-, and 10-year survival rates for the 457 completely responding limited-disease (LD-CR) patients were 19.6 months, 41%, 17%, and 5%, compared with 13.9 months, 26%, 8%, and 5%, respectively, for the 200 completely responding extensive disease (ED-CR) patients (P = .0001). Multiple prognostic factors, including whether the patient did or did not receive PCI (30 to 38 Gy in 2- to 3.6-Gy fractions) were analyzed. In both univariate and multivariate analyses, PCI was not associated with improved (or worsened) survival. The brain relapse rate was 37% for LD-CR patients who did not receive PCI versus 9% for those who did (P = .0001). In ED-CR patients, the brain relapse rate was 31% without PCI and 8% with (P = .009). Essentially all patients who developed brain relapse died within 2 years, with a median survival time of 3.7 months following relapse. Severe, life-threatening, or fatal CNS toxicity occurred in approximately 3% of patients who received PCI. CONCLUSION: The use of PCI remains controversial outside the setting of a clinical trial.

Aged↗
PubMed1994

Measurable or assessable disease in lung cancer trials: does it matter?

PURPOSE: The goals of this study were to analyze and compare the major clinical response rates and survival of patients with either measurable or assessable disease status to treatment with systemic chemotherapy. PATIENTS AND METHODS: All patients had stage IIIB or IV non-small-cell lung cancer (NSCLC) and were enrolled onto three consecutive phase III clinical trials. Patients were stratified by disease status (measurable or assessable) before randomization to systemic chemotherapy. The three trials were conducted in the setting of a multicenter cooperative oncology group. Composite data were obtained for the three trials. Major clinical responses, time to progression, and survival were analyzed and compared in patients with measurable or assessable disease using standard statistical methods. RESULTS: Four hundred twenty-six patients were enrolled onto the three trials from June 1981 through August 1990. Measurable disease was present in 236 patients (55%) and assessable disease in 190 (45%). Each study was well balanced for the number of patients with measurable or assessable disease on either treatment regimen. A major clinical response was observed in 71 patients with measurable disease (30%; 95% confidence interval [CI], 24 to 36). Forty patients with assessable disease responded to treatment (21%; 95% CI, 16 to 28) (P = .04). The time to progression for all patients (P = .23) and for responders only (P = .10) was not significantly different based on disease status. Overall survival and survival of responders only was not significantly different, but patients with assessable disease tended to do better. Using multivariate analysis, sex and disease status had a borderline influence on the major response rate (P = .05). Performance score (PS) was the only factor that was significantly correlated with survival. CONCLUSION: NSCLC patients with assessable disease have major clinical response rates, time to progression, and survival that are similar to those of NSCLC patients with measurable disease. This study supports the inclusion of patients with assessable-disease lung cancer in both phase II and III trials conducted in the cooperative group setting.

Adult↗
PubMed1994

Limited-stage small-cell lung cancer: patterns of intrathoracic recurrence and the implications for thoracic radiotherapy.

PURPOSE: This analysis was performed to determine the most appropriate volume that should be encompassed by thoracic radiation treatments (TRTs) for patients with limited-stage small-cell lung cancer (LSSCLC) who have responded to initial chemotherapy. PATIENTS AND METHODS: A retrospective review of all patients (N = 67) with LSSCLC who were not entered onto a research protocol and were treated at our institution between the years of 1982 and 1990 was performed. Fifty-nine of 67 patients had adequate information regarding the size of the tumor before the start of chemotherapy (computed tomographic [CT] scan of chest or chest x-ray), the size of the tumor before TRT, and the TRT field size based on a simulation radiography. All 59 patients were treated with cyclophosphamide-based chemotherapy, and TRT was generally delivered concomitantly with chemotherapy following two to three cycles of chemotherapy alone. RESULTS: Of 59 patients, 28 were treated with TRT field sizes that encompassed postchemotherapy tumor volumes, and 31 patients were treated with TRT field sizes that encompassed prechemotherapy tumor volumes (defined as a volume that included at least a 1.5-cm margin on the prechemotherapy tumor volume). Nineteen patients had an intrathoracic recurrence of disease as the first site of recurrent small-cell carcinoma: 10 of 31 patients treated with TRT fields that encompassed prechemotherapy tumor volumes and nine of 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes. For the 28 patients treated with TRT fields that encompassed postchemotherapy tumor volumes, the greatest distance that the prechemotherapy tumor volume (without margins) extended beyond the edge of the TRT field was 0.5 to 5.0 cm, with a median of 2.5 cm. All 19 of the intrathoracic recurrences were in-field failures, although two patients (one prechemotherapy volume and one postchemotherapy volume) did have concurrent pleural effusions. CONCLUSION: These results indicate that the use of TRT fields that encompass postchemotherapy tumor volumes does not increase the risk of marginal failures or intrathoracic failures outside the TRT field.

Actuarial Analysis↗
PubMed1994

Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer.

PURPOSE: Hydrazine sulfate, an agent that appears to inhibit gluconeogenesis, has been studied in cancer patients for approximately 20 years. There was a recent resurgence of interest in this drug when subset analysis of a small placebo-controlled, double-blind, clinical trial reported improved survival among non-small-cell lung cancer patients with a good performance status who were randomized to receive this drug along with standard chemotherapy. PATIENTS AND METHODS: Patients on this trial had newly diagnosed, unresectable non-small-cell lung cancer and were treated with cisplatin and etoposide. In addition, they were randomized to receive hydrazine sulfate or placebo in a double-blind manner. RESULTS: A total of 243 patients were randomized. Response rates were similar in the two treatment arms. There were trends for worse time to progression and survival in the hydrazine sulfate arm. No significant differences were noted in the two study arms with regard to toxicity or quality of life (QL). CONCLUSION: This trial failed to demonstrate any benefit for patients who received hydrazine sulfate.

Antineoplastic Agents↗
PubMed1993

Immune response induced in small-cell lung cancer by maintenance therapy with interferon gamma.

BACKGROUND: Chemotherapy, with or without radiotherapy, results in a 30%-40% complete response rate in small-cell lung cancer (SCLC), but approximately 90% of patients who have complete remission die within 2 years after relapse with chemoresistant disease. Randomized clinical studies of maintenance chemotherapy after complete response have failed to demonstrate survival advantage. However, studies have shown that the human cytokine interferon gamma (IFN-gamma) induces immune response in humans, including T-cell activation and expression of class II major histocompatibility complex (HLA-DR) and receptor for the Fc portion of immunoglobulin on monocytes. It has also been demonstrated that recombinant IFN-gamma (rIFN-gamma) induces immunomodulation and has antiproliferative activity. PURPOSE: In vivo effects of rIFN-gamma treatment were characterized by flow cytometric analysis of peripheral blood mononuclear cells in patients with SCLC who received rIFN-gamma as maintenance treatment. METHODS: After induction chemotherapy and radiotherapy, 100 patients who achieved a complete remission were randomly assigned to receive rIFN-gamma at a dose of 0.2 mg (4 x 10(6) units) once a day, subcutaneously, for 6 months, or observation only. In 31 patients, peripheral mononuclear cells were obtained prior to the study and at weeks 4, 8, and 12 for serial monitoring of immune response. By flow cytometric analysis, we identified the lymphocyte and monocyte populations using characteristic differences in electronic volume and right-angle scatter. In these populations, we determined the mean fluorescence channel after staining for CD14 (antigen expressed on monocytes), CD3 (antigen expressed on T lymphocytes), and HLA-DR (HLA class II expressed by monocytes and activated lymphocytes). To determine the number of Fc receptors per cell, an Fc receptor assay was performed using the monocyte cell line U937 as a standard. RESULTS: At weeks 4, 8, and 12, expression of HLA-DR and Fc receptors on monocytes in patients who received rIFN-gamma was significantly higher than that in untreated patients, and the difference was statistically significant. The number of Fc receptors per monocyte consistently increased during the rIFN-gamma treatment and reached a fivefold elevation at week 12. There was no statistically significant difference in lymphocyte surface antigen expression between the treated and untreated groups. CONCLUSION: The dose of rIFN-gamma used in this study resulted in immune stimulation in patients with SCLC who had complete remission after induction therapy. The in vivo immunomodulatory activity of rIFN-gamma in such patients is characterized by a strong monocyte activation but no significant alteration in T-cell activation.

Aged↗
PubMed1993

Comparison of loss of heterozygosity patterns in invasive low-grade and high-grade epithelial ovarian carcinomas.

Loss of heterozygosity (LOH) studies were performed to investigate the genetic differences which separate low-grade (LG), high-grade (HG), and borderline epithelial ovarian carcinomas. Fresh tumor samples and blood were obtained from 58 patients (20 LG, 34 HG, and 4 borderline tumor specimens) undergoing surgery for ovarian carcinoma at Mayo Clinic. Tumors were graded using a modified Broder's classification with invasive grades 1 and 2 considered LG, invasive grades 3 and 4 considered HG, and tumors with no evidence of stromal invasion classified as borderline. Polymorphism analysis was performed using 76 restriction fragment length polymorphisms and variable number of tandem repeats and 59 microsatellite markers representing all chromosome arms. Chromosome arms 6p, 17p, 17q, and 22q were found to be frequently lost in LG as well as HG tumors. Chromosome arms 13q and 15q were lost to a significantly greater extent in HG tumors compared to LG neoplasms (P = 0.003 and P = 0.08, respectively). Conversely, 3p loss was seen more frequently with LG tumors (P = 0.02). The majority of LG tumors (65%) did not show frequent LOH in the allelotype analysis. In fact, a subset of 7 (7 of 20) LG tumors accounted for 76% of the total allelic loss in the LG category. These tumors showed LOH almost identical to that of the HG neoplasms. Borderline tumors showed a low rate of allelic loss. There were no common events found between borderline and invasive tumors. Our data suggest that most HG tumors and a subset of LG tumors share genetic alterations at putative tumor suppressor genes detected by LOH studies. Chromosome 6 and 17 losses appear to be early events while 13q and 15q losses appear to be critical late events. However, a majority of LG tumors appear to develop as a consequence of an alternative mechanism(s) which is not detected by LOH studies. Possibilities include: (a) inactivation of tumor suppressor genes without LOH; (b) dominant negative gene(s) in which only one allele requires mutation; and (c) changes in dominant acting oncogenes. This unidentified phenomenon may be operative in borderline tumors as well.

Alleles↗
PubMed1993

Pilot study of accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage III non-small cell lung carcinoma.

BACKGROUND: The primary goal of this study was to determine the incidence of severe or greater acute radiation toxicity, and secondarily, response, survival, and local control in patients with unresectable Stage IIIA or B non-small cell lung cancer treated with accelerated hyperfractionated thoracic radiation therapy (AHTRT). METHODS: From September, 1989 through March, 1990, 21 evaluable patients with unresectable Stage IIIA or B non-small cell lung cancer were treated with AHTRT, using 6000 cGy in 40 fractions of 150 cGy twice daily, 6 hours between fractions, with a 2-week break midway through treatment. RESULTS: Two patients (9.5%) had acute Grade 3 radiation esophagitis requiring intravenous hydration, and two patients (9.5%) had acute Grade 3 radiation pneumonitis requiring oxygen and steroids. Only one patient had chronic toxicity, a Grade 3 radiation pneumonitis. Five patients (24%) achieved a complete response, whereas eight (38%) had a partial response or regression. With minimum follow-up of nearly 3 years, 3 patients are alive and 18 are dead. The median survival time and 1-, 2-, and 3-year survival rates were 10.8 months, 48%, 29%, and 14%, respectively. Local control was achieved in 11 of 21 (52%) patients. CONCLUSIONS: This AHTRT regimen can be given with an acceptable incidence of acute radiation toxicity. Response, survival, and local control rates in this unfavorable group of patients are encouraging. A North Central Cancer Treatment Group Phase III study of standard thoracic radiation therapy (6000 cGy in 30 fractions of 200 cGy daily) versus AHTRT (+/- chemotherapy) is now open.

Aged↗
PubMed1993

A randomized phase II trial of amonafide or trimetrexate in patients with advanced non-small cell lung cancer. A trial of the North Central Cancer Treatment Group.

BACKGROUND: In an effort to identify new active chemotherapeutic agents against non-small cell lung cancer (NSCLC), the authors conducted a randomized Phase II trial to evaluate the efficacy of amonafide or trimetrexate in patients with Stage IV disease. METHODS: This was a multicenter Cooperative Oncology Group trial. All patients had advanced NSCLC and were previously untreated with chemotherapy. Patients were randomized to treatment after enrollment. Amonafide was administered as a 24-hour continuous infusion (1600 mg/m2) every 21 days. Trimetrexate (150 mg/m2) was administered intravenously over 30 minutes every 2 weeks. The primary endpoints of the study were clinical response and toxic effects. All patients were observed for survival. RESULTS: Thirty-five patients received amonafide and were assessable. There were no complete responses and two partial responses (6%). Thirty-seven patients were treated with trimetrexate. There were no complete responses and five (14%) partial responses. Myelosuppression was the primary toxic effect observed with amonafide treatment. Trimetrexate was associated infrequently with clinically significant side effects. CONCLUSIONS: Amonafide is inactive against NSCLC, and no additional studies with this agent are planned. Trimetrexate has some activity against NSCLC, but its role in the future therapy of this disease is questionable.

Adenine↗
PubMed1993

Nonparametric estimation for the difference or ratio of median failure times.

A simple and purely nonparametric confidence interval procedure for the difference or ratio of two median failure times is proposed with censored observations. The new proposal does not involve unstable and complicated nonparametric density estimates and is valid asymptotically even when the two underlying distribution functions differ in shape. Extensive numerical studies are carried out to examine the appropriateness of the new procedure for practical sample sizes.

Colonic Neoplasms↗
PubMed1992

A phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin for metastatic squamous cell lung carcinoma.

BACKGROUND: In an effort to confirm the efficacy of mitomycin C against metastatic squamous cell lung carcinoma and to compare the efficacy of single-agent therapy with a combination containing cisplatin, the authors conducted a randomized Phase III trial of mitomycin C alone versus mitomycin C, vinblastine, and cisplatin (MVP). METHODS: All patients had advanced squamous cell lung carcinoma, and survival was the primary end point. There were 133 eligible patients who received either mitomycin C alone (n = 64) or MVP (n = 69). The two groups were similar with respect to performance score, disease status, age, sex, and stage. RESULTS: The major objective response rates were 30% (95% confidence interval [CI], 18-41%) and 43% (95% CI, 32-55%) for mitomycin C alone and MVP, respectively (P = 0.1). The median time to progression was 83 days for mitomycin C alone, compared with 119 days for MVP (P = 0.026). The median survival time was 114 days for mitomycin C and 163 days for MVP (P = 0.09). The 1-year survival rates were equivalent. Myelosuppression was the major toxicity, and there were significantly greater leukocyte nadirs with MVP therapy (P < 0.001). CONCLUSION: Mitomycin C has antitumor activity against squamous cell lung carcinoma when used alone or in combination with MVP. The regimen containing cisplatin had marginally increased activity that did not translate into a clinically significant survival advantage.

Adult↗
PubMed1992

Radiation therapy for diabetes insipidus caused by Langerhans cell histiocytosis.

Hypothalamic-pituitary radiation therapy has been the standard treatment for the diabetes insipidus of Langerhans cell histiocytosis. The goal of this study was to assess the role of radiation therapy in Langerhans cell histiocytosis-associated diabetes insipidus and to compare the results with nonirradiated controls. Forty-seven patients with pathologically confirmed Langerhans cell histiocytosis were diagnosed with diabetes insipidus between 1950 and 1989 and were treated at the Mayo Clinic. These patients were divided into two groups on the basis of treatment for the diabetes insipidus: The first group (radiation group) included 30 patients (28 of whom were evaluable for response) who received hypothalamic-pituitary radiation therapy, and the second group (control group) included 17 patients who did not. A partial response to treatment was defined as a reduction in vasopressin dosage or improvement in computed tomography (CT) or magnetic resonance imaging (MRI). A complete response was defined as no further need for vasopressin therapy or normalization of CT or MRI. End points analyzed included treatment response, patient characteristics, morbidity, dose-response relationship, and survival. Patient characteristics of the two groups were similar except for age and lung involvement, both of which were significantly less in the radiation group. Thirty-six percent of patients (10 of 28) in the radiation group responded to hypothalamic-pituitary radiation therapy (22% complete response and 14% partial response), whereas none in the control group responded. Five of the six complete responders were irradiated within 14 days of the diagnosis of diabetes insipidus. The mean dose used in the responding and nonresponding patients was 11.2 and 10 Gy, respectively. Three of five patients (60%) treated with more than 15 Gy responded compared to seven of 23 (30%) treated with less than 15 Gy. Eight of the 10 responders (80%), compared to 16 of 35 nonresponders (46%), were female. Only one in 20 patients with concomitant lung histiocytosis responded. Complications of therapy may include insufficiency in other hypothalamic-pituitary axes in the treated patients. Actuarial survivals at 5, 10, 20, and 40 years for the entire group were 80%, 78%, 75%, and 65%, respectively, with a median follow-up in living patients of 14.7 years.

Adolescent↗
PubMed1992

Group sequential distribution-free methods for the analysis of multivariate observations.

Many studies involve the collection of multivariate observations, such as repeated measures, on two groups of subjects who are recruited over time, i.e., with staggered entry of subjects. Various marginal distribution-free multivariate methods have been proposed for the analyses of such multivariate observations where some measures may be missing at random. Using the multivariate U statistic of Wei and Johnson (1985, Biometrika 72, 359-364), we describe the group sequential analysis of such a study where the multivariate observations are observed sequentially--both within and among subjects. We describe a multivariate generalization of the Hodges and Lehmann (1963, Annals of Mathematical Statistics 34, 598-611) estimator of a location shift that can be obtained via the multivariate U statistic with the Mann-Whitney-Wilcoxon kernel. We then describe large-sample group sequential interval estimators and tests based on an aggregate estimate of the location shift combined over all of the repeated measures. We also describe how the same steps could be employed to perform a group sequential analysis based on any one of the variety of marginal multivariate methods that have been proposed. These methods are applied to a real-life example.

Biometry↗