Search PubMed⌕ Search

Biomedical subjects

S Dahlberg

Publications and source records attributed to S Dahlberg.

At least 37 records · Page 2Linked to original sources
PubMed1993

Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy.

PURPOSE: We reviewed survival data of patients with low-grade lymphoma entered on Southwest Oncology Group (SWOG) lymphoma trials in 1972 to 1983 to determine the utility of doxorubicin-containing therapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP]) in such patients. PATIENTS AND METHODS: We identified all patients with low-grade lymphoma, no prior therapy, and stage III or IV disease who were treated with full-dose CHOP induction therapy on any arm of SWOG studies 7204, 7426, or 7713. Survival data for this group of patients were correlated with pretreatment prognostic factors, including histology, patient age, sex, symptom status, performance status, bone marrow or extranodal involvement, and the number of disease sites. The effect of maintenance treatment was also assessed. RESULTS: Four hundred fifteen patients met criteria for inclusion in the study group. With median follow-up periods of 12.8 years (maximum, 19.8 years), the median survival duration was 6.9 years. Survival was significantly shorter in patients with follicular mixed or small lymphocytic histology, age greater than 40 years, male sex, B-symptom status, and SWOG performance status greater than 1. Multivariate regression analysis showed histology, age, and sex to be independent predictors of survival. There was no definite survival plateau of cured patients in any subgroup, although the survival curve for follicular mixed histology patients showed long-term survival of approximately 25%. Maintenance therapy did not prolong survival. CONCLUSION: Doxorubicin-containing treatment did not prolong the overall median survival of low-grade lymphoma patients compared with results with less-aggressive programs.

Adult↗
PubMed1993

Selection designs for pilot studies based on survival.

In cancer clinical trials new regimens are typically tested for antitumor activities in patients with advanced disease. The promising ones are then compared to the standard treatment in a randomized study, sometimes performed on patients with earlier-stage disease. When there are multiple promising regimens, it may not be possible to compare all of them to the control group because of the prohibitive sample size and study length requirements. We propose a design that uses the Cox regression model to select a best treatment based on survival before the randomized comparison. Sample sizes for an asymptotically correct selection probability of .90 are presented for Weibull survival distributions with parameters in a range we consider to be of practical interest. Simulations verify that the asymptotic approximations to the correct selection probabilities are quite satisfactory. Simulations also indicate that the procedure is reasonably robust to the proportional hazards assumption. In contrast to the two-stage screening design recommended by Schaid, Wieand, and Therneau (1990, Biometrika 77, 507-513), our design has the advantage of fitting naturally to a progression of cancer trials where the selection and comparison phases are carried out on different populations of patients. When the population of interest stays the same, our design can be more conservative on the average but offers the opportunity to base the comparative trial on the experience gained during the selection phase.

Clinical Trials as Topic↗
PubMed1992

Planned versus attained design in phase II clinical trials.

The standard phase II trial problem is to decide whether or not to continue the testing of a new agent (or combination). Typically, one tests the null hypothesis HO: p = pO against the alternative HA: p = pA, where p is the probability of response. There is available a variety of two-stage phase II designs, including optimal designs according to various criteria. Practical considerations in the conduct of multicentre trials, however, make it difficult to follow designs precisely. We investigate several approaches to adapting stopping rules when the attained sample size is not the planned size. We find that a simple approach of testing HA: p = pA at the 0.02 level at the first stage and HO: p = pO at the 0.055 level at the second stage works well across a variety of powers, pOs and pAs.

Decision Making↗
PubMed1992

Prognostic factors in clinical trials.

Prognostic factors define the study population, help formulate the study objectives, and influence the treatment strategies. They must be accounted for in the study analysis to obtain valid estimates of the treatment differences and to evaluate results across studies. The causal relationship between a prognostic factor and the study endpoint can only be established through prospective randomized study designs. Potential factors discovered through retrospective analysis must be verified to establish their validity. Using such factors prematurely to select patient population and treatment strategy for a new study will not establish the validity of the potentially important factor.

Clinical Trials as Topic↗
PubMed1992

Predictors of surgical mortality and long-term results of endocardial resection for drug-refractory ventricular tachycardia.

The results of surgical therapy performed in 51 consecutive patients with ventricular tachycardia were reviewed to determine short- and long-term predictors of success of such therapy in preventing recurrences of life-threatening ventricular arrhythmias. Of 41 patients (80%) who survived surgery, 40 had postoperative programmed stimulation and, of these patients, 78% (n = 31) had no inducible ventricular tachycardia on no antiarrhythmic therapy. This group had a very low incidence of arrhythmia recurrence, with only one nonfatal episode of ventricular tachycardia after a mean follow-up of 41 +/- 30 months. In contrast, two of the nine patients (22%) who had inducible arrhythmias postoperatively had cardiac arrest (p = 0.12). Multivariate analysis identified two significant predictors of perioperative mortality in our patients: increased duration of cardiopulmonary bypass time and increased baseline pulmonary capillary wedge pressure. It is concluded that (1) patients who do not have inducible ventricular tachycardia after arrhythmia surgery have a very low incidence of recurrent arrhythmia and (2) prolonged time of cardiopulmonary bypass and increased pulmonary capillary wedge pressure are predictive of perioperative mortality.

Adult↗
PubMed1992

Focal myocardial injury following blunt chest trauma: a comparison of indium-111 antimyosin scintigraphy with other noninvasive methods.

The diagnosis of myocardial contusion is often difficult, as traditional methods such as serial electrocardiograms, cardiac enzyme (creatine kinase [CK-MB]) analysis, and echocardiography lack sensitivity and specificity. Recent reports have shown that 111In labelled antimyosin scanning has high sensitivity for detecting cardiac injury. However, no prior studies have been reported for antimyosin imaging with patients suspected of sustaining a cardiac contusion. Accordingly, 17 patients with severe multisystem trauma (intrathoracic vascular injury in eight patients, pneumothorax and pulmonary contusion in 13) underwent antimyosin scintigraphy, echocardiography, 12-lead electrocardiograms, and CK-MB determinations. Arrhythmias were noted in seven patients, four of whom died. All patients has elevated CK levels but CK-MB isoenzyme was greater than 4% in only three. Abnormal ST segments were noted in nine subjects, only one of whom had CK-MB elevation. Echocardiography revealed pericardial effusions in four patients but was technically suboptimal in 53% of the studies. Blinded interpretation of the antimyosin scans revealed only one with focal myocardial uptake; this same patient had the only discrete wall motion abnormality on the echocardiogram and also had ST depression with ectopy but normal CK-MB. Thus in patients with suspected myocardial contusion, echocardiography is frequently limited technically and the electrocardiogram and CK analysis appear to lack diagnostic accuracy. In contrast, monoclonal antimyosin imaging may be performed in patients with trauma without limitation and yields results that are concordant with echocardiograms. In patients with suspected myocardial contusion, focal antimyosin uptake is uncommon despite severe thoracic injury, which suggests that extensive myocardial necrosis is not the primary method of injury.

Adult↗
PubMed1992

A comparison of two-dimensional echocardiography vs carotid duplex scanning in older patients with cerebral ischemia.

BACKGROUND: To determine the relative value of two-dimensional (2D) echocardiography vs carotid duplex scanning and to devise an optimal, cost-effective diagnostic approach for older patients with cerebral ischemia, 68 consecutive patients in sinus rhythm who suffered focal cerebral ischemia were studied. All patients underwent 2D echocardiography and carotid duplex scanning in addition to routine clinical evaluation. METHODS: Twenty-five of 68 patients had Q-wave myocardial infarction by electrocardiography; nine (36%) of these 25 had left ventricular mural thrombi demonstrated by 2D echocardiography. In contrast, none of 43 patients without Q-wave myocardial infarction had clinically unsuspected findings diagnosed by 2D echocardiography. Duplex scanning, however, identified significant, abnormal findings in the carotid artery ipsilateral to the involved cerebral hemisphere in 23 patients (34%). CONCLUSIONS: Thus, in older patients in sinus rhythm who suffer a cerebral ischemic event, carotid duplex scanning has a higher diagnostic yield than 2D echocardiography and appears to be a more cost-effective initial test. Our data suggest that in patients with carotid distribution cerebral ischemic events and no obvious cardiac source for emboli by history and physical examination, 2D echocardiography should be limited to those with evidence of Q-wave myocardial infarction by electrocardiography; such management should optimize diagnostic yield and cost effectiveness.

Aged↗
PubMed1991

Combination chemotherapy of intermediate-grade and high-grade non-Hodgkin's lymphoma with MACOP-B: a Southwest Oncology Group study.

One hundred nine assessable patients with measurable stage II, III, or IV intermediate- or high-grade lymphoma were treated with methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) by members of the Southwest Oncology Group (SWOG) between November 1985 and June 1986 to confirm the activity of the program as initially described by Klimo and Connors and to test the safety of using third-generation regimens in a cooperative group. The median age was 53.5 years, and stage II was seen in 30% of patients and diffuse large-cell histology in 63%. Complete remission (CR) was achieved in 50% of all patients and partial remission (PR) in 33%. Response rates did not differ by histology. Median follow-up is 46 months with 51% of patients alive at 3 years and 63% of CR patients free of disease at 3 years. Severe (grade 3) or worse hematologic toxicity was seen in 51% of all treated individuals, and 29% had severe mucositis. We failed to confirm the high response rates as originally reported. Whether MACOP-B is superior to other treatment regimens requires the prospective trial currently being conducted by the SWOG.

Aged↗
PubMed1991

Activity of esorubicin in recurrent malignant lymphoma: a Southwest Oncology Group study.

A phase II trial of esorubicin (4' deoxydoxorubicin) was conducted by the Southwest Oncology Group in 88 assessable patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) at the time of first relapse. Esorubicin was administered at two dose levels: 25 mg/m2 for patients at risk for excessive myelosuppression, and at 30 mg/m2 for all others at 21-day intervals. Overall, 33 of 88 patients (38%) responded to treatment including three complete remissions (CRs; 3%) and 30 partial remissions (PRs; 34%), with the median duration of response lasting 6.2 months. Response rates did not differ significantly by histologic subtype: 31% of 26 patients with favorable NHL, 33% of 43 patients with unfavorable NHL, and 58% of 19 patients with HD. Twelve of 33 responding patients (36%) had relatively durable remissions lasting from 1 to more than 4 years. Leukopenia (less than 3,000 cells per microliter) was seen in 65 of 88 patients (74%) and was severe (less than 1,000 cells per microliter) in 20 of 88 patients (23%). Clinical signs or symptoms of congestive heart failure were not seen and the ejection fraction (EF) fell 10% to 20% in three patients. Esorubicin is an active agent in patients with NHL or HD at the time of first relapse.

Adult↗
PubMed1991

Alternated versus syncopated CHOP-PVB: two studies for the treatment of non-Hodgkin's lymphoma by the Southwest Oncology Group.

Based on a preliminary trial that suggested that CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), and PVB (cisplatinum, vinblastine, bleomycin), are at least partially non-cross-resistant, the Southwest Oncology Group treated patients with unfavorable histology, non-Hodgkin's lymphoma with CHOP and PVB. In the first study, 76 eligible patients were given three courses of CHOP, with complete or partial responders receiving three courses of PVB followed by three further courses of CHOP. Nonresponders after the initial three cycles of CHOP, received six courses of PVB. In the second study, 154 eligible patients were treated with alternating cycles of the two drug regimens. The overall objective antitumor response (CR + PR) was 77% for the first study and 58% for the second. The complete remission rates were 48% and 38%, respectively. The overall survival for both studies is similar. These results are interpreted in terms of the Goldie-Coldman hypothesis.

Antineoplastic Agents↗
PubMed1990

Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion.

The limiting toxicity of low dose continuous infusion 5-fluorouracil (200-300 mg/m2/day) is often palmar-plantar erythrodysesthesia (PPE). PPE developed in 16/25 patients (exact 95% confidence interval of 42%-82%) with metastatic colon cancer enrolled in a phase II trial. In this trial, 5-FU was given continuously at a dose of 200 mg/m2/day until toxicity or progressive disease forced discontinuation. The first signs of the syndrome developed at a median of 2 months following infusion initiation and, unless treatment was interrupted, became progressively worse. The incidence of moderate to severe PPE was 71% in the 14 previously untreated patients (exact 95% confidence intervals of 42-92%). Seventy-eight percent of the responders in the no prior treatment group developed PPE. The incidence of moderate to severe PPE was only 27% in the 11 previously treated patients (exact 95% confidence intervals of 6-61%). The higher incidence of PPE in the previously untreated patients probably resulted from a longer total infusion time (median = 7.3 months) than the previously treated (median = 4.5 months). The longer infusion time in turn was a result of the higher response rates (64 vs 18%) in the previously untreated versus treated groups. Five previously untreated patients who developed PPE received 50 or 150 mg of pyridoxine/day when moderate PPE changes were noted. Reversal of PPE without interruption of the 5-FU was seen in 4/5 patients. Four of these patients who received pyridoxine had responded to 5-FU treatment. No adverse affect of pyridoxine on clinical response was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Colonic Neoplasms↗
PubMed1990

Unfavorable histologies of non-Hodgkin's lymphoma treated with ProMACE-CytaBOM: a groupwide Southwest Oncology Group study.

Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE-CytoBOM) for patients with intermediate- and high-grade non-Hodgkin's lymphomas was tested by the Southwest Oncology Group (SWOG) to confirm the activity of the regimen and to test the feasibility and safety of administering third-generation drug regimens in a cooperative group setting. On day 1, cyclophosphamide, doxorubicin, and etoposide were administered, followed by cytarabine, bleomycin, vincristine and methotrexate with leucovorin given on day 8. There were 51 complete remissions (CRs) among 78 previously untreated patients (65%) having clinical stage II-IV disease. The median length of follow-up is 37.9 months with 57% of patients alive at 3 years and 50% of CR patients free of disease at 3 years. Patients with diffuse large-cell lymphoma have the best survival (63% at 3 years) and relapse-free survival (RFS; 68% at 3 years with no relapses seen after 14 months). Administration of ProMACE-CytoBOM is feasible and safe in a cooperative group setting with 84% of 537 courses of treatment given exactly according to schedule and fatal toxicities seen in five patients (6%). ProMACE-CytaBOM may represent improved treatment for diffuse large-cell lymphoma, but the modest differences compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) indicate the need for a prospective randomized comparative trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

m-BACOD treatment for intermediate- and high-grade malignant lymphomas: a Southwest Oncology Group phase II trial.

One hundred six eligible patients with advanced intermediate- or high-grade malignant lymphoma were treated with methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) in a Southwest Oncology Group phase II trial. Patients were stratified by estimated bone marrow reserve, and impaired marrow reserve patients received reduced doses of cyclophosphamide and doxorubicin. The complete remission rate for normal marrow reserve patients was 65%, while the complete remission rate for impaired marrow reserve patients was 29%. With a median follow-up period of 41 months, 64% of complete responders in the normal marrow group are disease-free 3 years after their response. Three-year survival is 61% in the normal marrow reserve group and is 29% in the impaired marrow reserve group. Eighty-seven percent of treatment courses were given in accordance with protocol dosing and schedule. For doxorubicin, relative dose intensities were 0.75 and 0.61 (normal and impaired marrow reserve arms, respectively), for cyclophosphamide, 0.76 and 0.61, and for methotrexate, 0.55 and 0.45. Serum lactic dehydrogenase (LDH) level was the only pretreatment characteristic found to have a significant effect on overall survival. Severe or greater toxicity occurred in 97% and 89% of the normal and impaired marrow reserve groups, respectively, with granulocytopenia the principal toxicity. Treatment-related fatalities occurred in 8% of patients. m-BACOD is an effective but toxic treatment program for intermediate- and high-grade malignant lymphomas.

Adolescent↗
PubMed1989

Mitoxantrone, cisplatin, and methyl-glyoxal bis-guanylhydrazone chemotherapy for refractory malignant lymphoma: a Southwest Oncology Group phase II trial.

A phase II trial of combination chemotherapy with mitoxantrone, cisplatin, and methyl-glyoxal bix-guanylhydrazone (MGBG) was conducted in 32 patients with unfavorable histology malignant lymphoma. All patients had relapsed after only one prior chemotherapy regimen (CHOP--56%; mBACOD--28%). There were three complete and eight partial responses (overall response rate--34%) among 32 eligible patients. The median duration of remission was 6.0 months. Severe granulocytopenia was common, with 19/32 patients (63%) suffering life-threatening, and 1/32 (3%) suffering fatal, granulocytopenia. We conclude that mitoxantrone-cisplatin-MGBG has modest activity as salvage treatment in malignant lymphoma patients, but produces severe toxicity.

Adolescent↗
PubMed1989

Phase II evaluation of bisantrene in acute leukemia. A Southwest Oncology Group Study.

Twenty-nine patients with heavily pretreated acute leukemia in relapse were treated with bisantrene (maximum dose 120 mg/m2/day x 5) in a phase II study. Twenty-seven of the 29 patients were evaluable for response, receiving a total of 53 courses of treatment. There were three complete remissions (11%) lasting 27, 107, and 115 days. One brief partial remission of 43 days was also seen for a total response rate of 15%. Toxicity was mainly limited to the expected myelotoxicity with minimal nonhematologic toxicity seen. Although the complete remission rate is low, an antileukemic effect was seen in the majority of the patients treated. Sixty-one percent of the patients had at least a 50% decrease in the circulating blast count and 32% had at least a 50% decrease in the number of bone marrow blasts. We conclude that bisantrene does have an antileukemic effect, but that the optimal starting dose is not yet established.

Acute Disease↗