Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.

BACKGROUND: In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. PATIENTS AND METHODS: In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . RESULTS: Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. CONCLUSION: Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.

Baseline tumour measurements predict survival in advanced non-small cell lung cancer.

BACKGROUND: The association between tumour measurements and survival has been studied extensively in early-stage and locally advanced non-small cell lung cancer (NSCLC). We analysed these factors in patients with advanced NSCLC. METHODS: Data were derived from the E4599 trial of paclitaxel-carboplatin±bevacizumab. Associations between the Response Evaluation Criteria in Solid Tumors (RECIST) baseline sum longest diameter (BSLD), response rate, progression-free survival (PFS) and overall survival (OS) were evaluated using univariate and multivariable Cox regression models. RESULTS: A total of 759 of the 850 patients (89%) in the E4599 trial had measurable diseases and were included in this analysis. The median BSLD was 7.5 cm. BSLD predicted OS (hazard ratio (HR) 1.41; P<0.001) and had a trend towards association with PFS (HR 1.14; P=0.08). The median OS was 12.6 months for patients with BSLD <7.5 cm compared with 9.5 months for BSLD ≥ 7.5 cm. This association persisted in a multivariable model controlling multiple prognostic factors, including the presence and sites of extrathoracic disease (HR 1.24; P=0.01). There was no association between BSLD and response rate. CONCLUSION: Tumour measurements are associated with survival in the E4599 trial. If validated in other populations, this parameter may provide important prognostic information to patients and clinicians.

Race, socioeconomic status, and other prognostic factors for survival from prostate cancer.

Survival data on prostate cancer patients from 11 Comprehensive Cancer Centers contributing data to the Centralized Cancer Patient Data System were analyzed to examine the contribution of various factors to the probability of survival from prostate carcinoma. Application of a number of exclusion criteria resulted in a series of 2,513 patients (1,032 blacks and 1,481 Caucasians) for whom complete data on variables of interest were available. The stage of disease at diagnosis was a major determinant of survival. The proportion of blacks presenting the disease in advanced stage was substantially higher than that of Caucasians--a difference which was maintained within each socio-economic status (SES) category. Caucasian patients had a better prognosis than blacks for each disease stage. A dose-response relationship between SES and survival prognosis was observed and this relationship persisted for each stage of the disease. Although both race and SES turned out to be significant in regression models in which one or the other was considered, the model including both race and SES showed only SES to be a significant factor. Hence it can be hypothesized that the racial difference in the survival prognosis for prostate cancer is, to a large extent due to the differences in the distribution of SES in the two races.

Accuracy of basic cancer patient data: results from an extensive recoding survey.

The accuracy of data coded from the medical records of 985 patients from 22 major U.S. cancer centers was checked by recoding during 1978-81. The 29 items covered demographics, diagnosis, and therapy. Original codes were compared to recodes, and disagreements were classified as major or minor. The highest rate of major disagreements, 23%, was for stage of disease, followed by 10% for histology and 7% for site. Major disagreement rates for most other items were under 7%. Only 3% of a large sample of major disagreements involved justifiable differences in interpretation; the others were due to errors in the use of records. Major disagreement rates varied by a factor of 10 across sites, 4 across centers, and 2 across stage of disease. For several items the code "unknown" was overused and led to disagreements. A new procedure is presented for analysis of disagreement rates. The results from this procedure can guide training effort to improve coding accuracy.

Hodgkin's disease in the United States: a comparison of patient characteristics and survival in the Centralized Cancer Patient Data System and the Surveillance, Epidemiology, and End Results Program.

Demographic, pathologic, and clinical characteristics as well as subsequent survival were compared between 3,607 Hodgkin's disease (HD) patients registered by the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute and 2,278 HD patients registered by comprehensive cancer centers (CCCs) belonging to the Centralized Cancer Patient Data System (CCPDS). All patients were diagnosed with HD between July 1977 and December 1982. CCPDS cases were slightly younger, more often of the nodular sclerosing histologic type, and presented with Stage II disease at diagnosis more often than did SEER cases. CCPDS and SEER cases were similar regarding the lymph node region of origin, sex, and race. The mortality rate among SEER patients was approximately 1.5 times that among CCPDS patients. This significant survival difference was observed within all stages and within all histologic subtypes and remained after controlling for the effects of age. Late-stage, older age, non-Caucasian race, and a more diffuse histologic appearance were all independent and significant predictors of poor survival. These findings suggest that the management of HD in CCCs results in improved outcome relative to that in the general population. Possible explanations for such effects are explored, and additional lines of pursuit are suggested.

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.

Analysis of prognostic factors for the outcome of marrow transplantation or further chemotherapy for patients with acute nonlymphocytic leukemia in first remission.

To test whether variables at diagnosis can identify patients with acute nonlymphoblastic leukemia (ANL) for whom bone marrow transplantation (BMT) is more likely to be of benefit and those for whom continued chemotherapy is a better approach, the association of 15 clinical and laboratory factors with outcome was investigated among 220 patients (ages 1 to 53 years) treated with cyclophosphamide and total body irradiation (TBI) followed by allogeneic BMT, and among 392 patients (ages 13 to 50) administered intensive chemotherapy. In the BMT group, female sex, younger age, the absence of hepatitis during induction, a larger percentage of circulating blasts, and a shorter duration of symptoms were associated with longer survival, whereas only female sex and younger age favorably influenced disease-free survival (DFS). In the chemotherapy group, younger age, lower WBC at diagnosis, a single successful induction course, and the absence of circulating promyelocytes were associated with longer survival, whereas only a lower WBC and a lower percentage of peripheral neutrophils were associated with longer DFS. Estimated regression coefficients for treatment-by-prognostic-factor interactions were used to characterize subgroups of patients in which one treatment or the other produced better outcomes. BMT and chemotherapy produced similar durations of survival in a subset of patients characterized by many or all of the following: older age, male sex, achievement of complete remission (CR) after one induction, and absence of circulating blast cells at presentation. These data suggest that, using pretreatment variables, subgroups of patients can be identified for whom either BMT or continued chemotherapy is most likely to be beneficial.

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.

Autologous bone marrow transplantation for patients with relapsed or refractory diffuse aggressive non-Hodgkin's lymphoma: value of augmented preparative regimens--a Southwest Oncology Group trial.

PURPOSE: To determine the toxicity and prognosis of patients with relapsed and refractory diffuse aggressive non-Hodgkin's lymphoma (NHL) who underwent an autologous bone marrow transplant (ABMT) using augmented preparative regimens, treated in a major cooperative group setting, and to examine prognostic factors for outcome. PATIENTS AND METHODS: Ninety-four patients with either chemosensitive (50 patients) or chemoresistant (44 patients) relapse, including 22 who failed induction chemotherapy, were treated with high-dose cyclophosphamide and etoposide with total-body irradiation (TBI) (67 patients) or an augmented carmustine (BCNU), cyclophosphamide, and etoposide (BCV) preparative regimen (27 patients) and an ABMT at 16 Southwest Oncology Group (SWOG) transplant centers. All relapsing patients were required to undergo a minimum of two courses of salvage therapy to determine chemosensitivity before transplant. Overall (OS) and progression-free survival (PFS) were determined and a Cox regression model was used to assess potential prognostic variables. RESULTS: Of the 94 eligible patients, there were 10 (10.6%) deaths before day 50 posttransplant because of infection (six deaths), hemorrhagic alveolitis (three deaths), or bleeding (one death). The median 3-year PFS and OS for the entire group was 33% and 44%. For those with chemosensitive disease the PFS and OS were 42% and 55%, whereas for those with chemoresistant disease the PFS and OS were 22% and 29%. The PFS and OS for those failing induction chemotherapy were 27% and 32%. The relapse rates within the first 3 years for the chemosensitive relapse, chemoresistant, and induction failure groups were 61%, 40%, and 59%, respectively. For both PFS and OS, only disease status at transplant was a significant factor in the multivariate Cox model. CONCLUSION: These results single institutional pilot trials exploring augmented preparative regimens. Patients undergoing transplantation for resistant disease, particularly those failing induction chemotherapy, appear to have an improved prognosis as compared with reports using standard preparative regimens. Therapies other than manipulation of standard preparative regimens appear to be required to decrease relapses following autotransplantation.

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.

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.

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.

United States multicenter study of arsenic trioxide in relapsed acute promyelocytic leukemia.

PURPOSE: To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL). PATIENTS AND METHODS: Forty patients experiencing first (n = 21) or > or = second (n = 19) relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study. RESULTS: Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/microL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes. CONCLUSION: This study establishes ATO as a highly effective therapy for patients with relapsed APL.

Thallium reinjection versus standard stress/delay redistribution imaging for prediction of cardiac events.

OBJECTIVES: The purpose of this study was to compare thallium reinjection with standard stress/delay redistribution for the prediction of cardiac events. BACKGROUND: Although thallium reinjection enhances the detection of viable myocardium, its contribution to prognosis over stress/delay redistribution in a general referral population has not been clearly evaluated. METHODS: This retrospective analysis included 366 consecutive patients with coronary artery disease who underwent stress/delay redistribution imaging and thallium reinjection scintigraphy, with a mean follow-up of 33+/-12 months. RESULTS: Cardiac events occurred in 48 patients (40 deaths, 8 myocardial infarctions). Of the 366 original patients, 159 demonstrated ischemia by stress/delay redistribution, 107 showed ischemia by reinjection only, and 100 showed infarction only. Cardiac events occurred in 20 patients (12.6%) with stress/delay redistribution, 13 patients (12%) with ischemia detected by thallium reinjection only and 15 patients (15%) with infarction only. The size of the reversible thallium defect by either stress/delay redistribution imaging or reinjection scintigraphy did not predict cardiac events. Independent predictors of cardiac events included left ventricular cavity size, the size of the abnormal perfusion defect and patient age. CONCLUSIONS: Thallium reinjection does not contribute independent prognostic utility for cardiac events when compared with stress/delay redistribution. Left ventricular dilation and the size of the post-stress defect were predictors of cardiac events.

Sequential teboroxime imaging during and after balloon occlusion of a coronary artery.

OBJECTIVES: We sought to assess whether sequential teboroxime imaging can rapidly evaluate vessel patency and identify the coronary artery occluded in patients undergoing balloon occlusion of a coronary artery. BACKGROUND: Intravenous thrombolytic therapy results in successful reperfusion of the infarct-related artery in only 50% to 80% of cases. A noninvasive technique to serially evaluate coronary perfusion would identify patients who might benefit from other interventions such as emergency percutaneous transluminal coronary angioplasty, coronary artery bypass grafting or increased intensity of thrombolytic therapy. METHODS: Teboroxime scans were performed during balloon occlusion in 15 nonconsecutive patients undergoing angioplasty of a major coronary artery. Equivalent views were repeated after successful angioplasty. RESULTS: The mean time between balloon occlusion and reperfusion imaging was 1.6 +/- 0.6 h. The mean number of defects decreased significantly from 4.13 +/- 1.01 during balloon occlusion to 0.27 +/- 0.44 after reperfusion (p = 0.0006). There was a 30% decrease in the defect/normal zone count/pixel ratios during balloon occlusion and normalization of these ratios after reperfusion (p = 0.0006). The scans correctly identified all nine left anterior descending coronary artery occlusions and both right coronary artery occlusions. One of the four left circumflex coronary artery occlusions was incorrectly identified as a right coronary artery occlusion by scan criteria. Overall, the scans correctly identified the occluded artery 93% of the time (kappa = 0.88). The scan was 100% accurate for distinguishing occlusion of the left anterior descending coronary artery (n = 9) from occlusions of the left circumflex or right coronary artery (n = 6). CONCLUSIONS: We believe that this is the first clinical study to demonstrate that sequential planar imaging with teboroxime can 1) rapidly detect acute coronary artery occlusion and reperfusion, and 2) identify the occluded coronary artery. A trial comparing rapid sequential teboroxime imaging with coronary angiography in patients receiving thrombolytic therapy for acute myocardial infarction is warranted.

Bilateral brachial artery emboli presenting as aortic dissection.

Loss of peripheral pulses in a patient with chest pain suggests the diagnosis of aortic dissection. An 80-year-old woman presented with an episode of chest pain and acute bilateral loss of upper extremity pulses that was initially treated as aortic dissection. Findings of physical examination and echocardiography were consistent with mitral stenosis. Angiography revealed bilateral brachial artery emboli, which were treated by embolectomy. To our knowledge, this case represents the first report of simultaneous brachial artery emboli in association with mitral stenosis.

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.

Long-term outcome of a pediatric-inspired regimen used for adults aged 18-50 years with newly diagnosed acute lymphoblastic leukemia.

On the basis of the data suggesting that adolescents and young adult patients with acute lymphoblastic leukemia (ALL) have improved outcomes when treated on pediatric protocols, we assessed the feasibility of treating adult patients aged 18-50 years with ALL with the DFCI Pediatric ALL Consortium regimen utilizing a 30-week course of pharmacokinetically dose-adjusted E. coli L-asparaginase during consolidation. Between 2002 and 2008, 92 eligible patients aged 18-50 years were enrolled at 13 participating centers. Seventy-eight patients (85%) achieved a complete remission (CR) after 1 month of intensive induction therapy. With a median follow-up of 4.5 years, the 4-year disease-free survival (DFS) for the patients achieving a CR was 69% (95% confidence interval (CI) 56-78%) and the 4-year overall survival (OS) for all eligible patients was 67% (95% CI 56-76%). The 4-year DFS for the 64 patients who achieved a CR and were Philadelphia chromosome negative (Ph-) was 71% (95% CI 58-81%), and for all 74 Ph- patients the 4-year OS was 70% (95% CI 58-79%). We conclude that a pediatric-like treatment strategy for young adults with de novo ALL is feasible, associated with tolerable toxicity, and results in improved outcomes compared with historical regimens in young adult patients with ALL.

Southwest Oncology Group clinical trials for intermediate- and high-grade non-Hodgkin's lymphomas.

The Southwest Oncology Group (SWOG) began testing doxorubicin-containing combination chemotherapy in 1972 using the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen. Subsequent studies, including 350 patients followed for up to 13.3 years, demonstrated that CHOP was curative in 32% of advanced stage, diffuse large cell lymphomas. More recently, promising results from several institutions suggest that new combinations including methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone (m-BACOD), prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate (ProMACE-CytaBOM), and methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin (MACOP-B) may be superior to CHOP as gauged by complete response (CR) rates. Consequently, the SWOG developed a strategy to compare these regimens directly with CHOP. In 1984 the SWOG began testing these regimens in sequential group-wide phase II trials to confirm therapeutic activity, establish feasibility with regard to toxicity in a cooperative group setting, and gain experience using the complex schedules and dose-modification schemes. Those phase II studies have been completed, and preliminary results indicate that these regimens are active (CR rates, 53% to 65%) and feasible to administer in a cooperative group setting (fatal toxicity, 2% to 6%). We conclude that these three drug regimens can be administered safely in a cooperative group setting, and the CR rates support the current SWOG comparative trial using CHOP as the standard treatment arm.

Southwest oncology group clinical trials for intermediate- and high-grade non-Hodgkin's lymphomas.

Previous studies have established CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as the standard of comparison for treatment programs for patients with advanced stages of aggressive non-Hodgkin's lymphomas. Three sequential CHOP studies conducted by the Southwest Oncology Group (SWOG) showed a complete remission (CR) rate of 53% for 418 patients. This rate did not vary among the three studies. Median age was over 55 years. Relapse-free survival of CRs plateaued at 4 to 5 years. Approximately 21% of all patients in the first study and 33% of all patients in the following two studies are long-term survivors and presumed cured. Survival was clearly a function of patient age. Approximately 45% of all patients under age 55 at the time of treatment are cured by CHOP chemotherapy. To determine the toxicity, CR rate, and patient survival of m-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone), ProMACE-CytaBOM (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, cytarabine, bleomycin, vincristine, methotrexate), and MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin), SWOG initiated a series of phase II studies. Of 118 eligible patients in the m-BACOD study, the median age of 85 patients treated with the full-dose regimen was 54 years, while the median age of 33 patients who started therapy at reduced doses was 67 years. Fatal toxicity was observed in 6% of patients receiving full doses and 13% of those receiving reduced doses. Life-threatening toxicity occurred in 31% of patients on the full-dose regimen and 34% on the reduced-dose regimen. CR was 65% for full-dose treatment, but 27% for reduced doses.(ABSTRACT TRUNCATED AT 250 WORDS)