PubMed Health⌕ Search

Biomedical subjects

A T Skarin

Publications and source records attributed to A T Skarin.

At least 19 recordsLinked to original sources
PubMed1995

Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung.

PURPOSE: Although standard treatment of stage I non-small-cell lung cancer (NSCLC) consists of surgical resection alone, approximately 50% of clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large number of traditional pathologic and newer molecular markers have been identified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensively. METHODS: Criteria for study selection were English-language reports, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLG) were also reviewed. RESULTS: Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and several reports conclude that a specific biomarker may be, aside from clinical stage, the most powerful determinant of prognosis in NSCLC. However, little has been done to clarify the relationships between these newer biologic markers, classic clinicopathologic variables, and clinical outcome. CONCLUSION: At present, a firm conclusion regarding which biomarkers are most important in predicting outcome is not possible, and a model that reliably integrates all independent prognostic variables cannot be developed. A prospective trial is mandatory to address this issue, and a study design is suggested that would facilitate the development of a prognostic index, while simultaneously asking a therapeutic question. The development of a prognostic index would facilitate future trials in which only high-risk stage I patients could be targeted for investigation of postresection adjuvant treatment strategies.

Biomarkers↗
PubMed1993

High-dose combined alkylating agent therapy with autologous stem cell support and chest radiotherapy for limited small-cell lung cancer.

Although initially responsive to chemotherapy, patients with small-cell lung cancer (SCLC) almost invariably suffer relapse. Recurrent SCLC responds poorly to treatment. Previous trials using high-dose chemotherapy with bone marrow support have commonly used single agents or combined alkylating agents without chest radiotherapy. Among patients with limited disease receiving dose-intensive chemotherapy, locoregional relapse remained the predominant site of first failure. Recent phase II trials using intensive locoregional therapy (aggressive concurrent chemoradiotherapy) have resulted in promising survival. Our trial used combined alkylating agents with autologous marrow support and chest radiotherapy in patients with limited disease in response to conventional-dose induction chemotherapy. Of 19 patients treated, the actuarial survival was 56% with a median follow-up of 18 months following high-dose therapy. Patients who achieved complete or near-complete response prior to high-dose therapy enjoyed the best prognosis. Continued evaluation of intensive systemic and local therapy for SCLC is indicated.

Alkylating Agents↗
PubMed1992

Multimodality treatment of stage IIIA non-small-cell lung carcinoma: a critical review of the literature and strategies for future research.

PURPOSE AND DESIGN: Stage IIIA non-small-cell lung carcinoma (NSCLC) is composed of regionally advanced yet potentially resectable disease. Many trials have evaluated a variety of therapeutic strategies. Most have been single-arm phase II trials, although a number of comparative phase III trials have also been performed. This review critically evaluates the existing literature on the treatment of stage IIIA NSCLC, particularly the various multimodality approaches that have been used. RESULTS: A review of the existing literature does not establish the optimal treatment of stage IIIA NSCLC. Although radiation therapy alone remains the most commonly administered therapy for apparently unresectable disease, the status of radiation as a "standard" therapy can be seriously challenged based on existing data. Similarly, although a number of studies have established that surgical resection is clearly feasible in selected patients with stage IIIA disease, the efficacy of surgery also remains to be definitively established. Many studies have explored neoadjuvant chemotherapy, either in conjunction with radiation or surgery, with results that are best described as conflicting and controversial. CONCLUSIONS: Without question, randomized phase III trials are required at this time to define what is to be considered optimal treatment. An attempt is made to define the most important questions that should be addressed in future phase III trials. Additionally, a number of study designs are suggested to best answer the therapeutic questions posed.

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

Drug-related pulmonary toxicity in non-Hodgkin's lymphoma. Comparative results with three different treatment regimens.

Pulmonary toxicity may complicate the treatment of non-Hodgkin's lymphoma (NHL). The possible drug-related cause of pulmonary toxicity was investigated retrospectively in 207 NHL patients treated between 1981 and 1988 with three regimens containing cyclophosphamide with and without methotrexate or bleomycin: methotrexate, calcium, leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) (n = 134); methotrexate, calcium, leucovorin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-ACOD) (n = 43); or cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (n = 30) chemotherapy. These regimens contained the same drugs and were administered in the same schedule; the regimens differed primarily in the addition of bleomycin or methotrexate. Pulmonary toxicity occurred in 24 of 134 (18%) m-BACOD-treated and in six of 43 (14%) m-ACOD-treated patients (P = 0.65). Chest radiography revealed diffuse pulmonary infiltrates in 16 (67%) and six (100%) of the m-BACOD-treated and m-ACOD-treated patients with pulmonary toxicity, respectively. None of the CHOP-treated patients had pulmonary toxicity. The clinical features of pulmonary toxicity and the amount of chemotherapy administered before it occurred did not differ in patients treated with m-BACOD or m-ACOD, although the toxicity tended to be more severe in the m-BACOD group. Open lung or transbronchial biopsies done in six (38%) of the m-BACOD-treated and three (50%) of the m-ACOD-treated patients with pulmonary infiltrates revealed nonspecific pneumonitis compatible with drug-related toxicity. In summary, these results showed that pulmonary toxicity during m-BACOD and m-ACOD therapy occurred with similar frequency and clinicopathologic features. This suggested that bleomycin was not responsible uniquely for the pulmonary toxicity in m-BACOD-treated patients. That pulmonary toxicity was not observed in patients treated with CHOP suggested that methotrexate may play an important role in the pathogenesis of the pulmonary toxicity.

Adult↗
PubMed1990

Treatment of low-grade and intermediate-grade lymphoma with intensive combination chemotherapy results in long-term, disease-free survival.

To define the role of intensive combination chemotherapy in the treatment of low-grade or intermediate-grade lymphomas, the authors report results in 49 patients treated with intermediate-dose or high-dose methotrexate, bleomycin, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cytoxan (cyclophosphamide), vincristine, and dexamethasone (m/M-BACOD) with long-term follow-up. The complete response rate was 59% (29 of 49), including 67% (eight of 12) with low-grade and 57% (21 of 37) with intermediate-grade disease. The median survival for the entire group was 81 months. The 29 complete responders had a long median survival of 131 months. Forty-five percent (13 of 29) of the complete responders, 27% of the entire group, continue in remission with a median disease-free survival of 76 months. This includes five of 19 patients with diffuse poorly differentiated lymphoma, a disease generally characterized by early relapse. Twelve patients achieved a partial response and had a shorter median survival of 53 months, whereas nonresponders survived a median of less than 5 months. Late relapse was noted in patients with low-grade and intermediate-grade disease. Age (younger than or older than 60 years) was the only predictor of long-term survival. These data indicate very long disease-free survival can be achieved in low-grade and intermediate-grade lymphomas after attaining a complete remission. Intensive doxorubicin containing chemotherapy can be considered as an option for patients with advanced low-grade lymphoma but can only be proven to be superior to single-agent chemotherapy or no initial therapy by controlled randomized trails.

Adult↗
PubMed1990

The m-BACOD combination chemotherapy regimen in large-cell lymphoma: analysis of the completed trial and comparison with the M-BACOD regimen.

One hundred thirty-four assessable patients with stage II-IV large-cell lymphoma (LCL) were treated with the combination chemotherapy regimen methotrexate with leucovorin, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD) between July 1981 and May 1986. The m-BACOD regimen substituted moderate-dose methotrexate (200 mg/m2 x 2) for the high-dose methotrexate used in the preceding M-BACOD regimen; all other drugs were administered as with m-BACOD. Eighty-two patients (61%) in the completed m-BACOD trial achieved a complete response (CR). With a median follow-up of 3.6 years, 62 patients (76%) continue in CR. Predicted survivals of 1, 3, and 5 years for the entire m-BACOD group are 80%, 63%, and 60%, respectively, with a 5-year disease-free survival (DFS) of 74% for the patients who achieve CR. The results obtained with m-BACOD are comparable with those obtained in the preceding M-BACOD trial, which now has a median follow-up of 8.0 years. The reduction in methotrexate dosage in m-BACOD patients was not associated with an increased incidence of CNS relapse. Long-term follow-up of the 215 M/m-BACOD patients indicates that the regimens are not associated with an increased incidence of secondary malignancy. Prolonged follow-up also indicates that advanced-stage patients have a persistent rate of late relapse of about 7.0% per year for years 2 to 5 of their follow-up and that stage II patients have an approximate 2.1% per year rate of late relapse. Application of the previously described prognostic factor model to the 215 M/m-BACOD patients from the completed trials identifies a high-risk group of patients with a CR rate and predicted 5-year survival (38% and 24%, respectively) that are significantly worse than those of the group as a whole (65% and 57%, respectively).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Patterns of relapse in large-cell lymphoma patients with bulk disease: implications for the use of adjuvant radiation therapy.

In patients with large-cell lymphoma (LCL) treated with combination chemotherapy, the presence of bulk disease has consistently been associated with a poorer response rate and a shortened survival. The optimal therapy for patients with bulk disease (greater than or equal to 10 cm) will depend on whether treatment failures result from inadequate tumor eradication in prior bulk sites or from distant dissemination. To address this issue, we have evaluated patterns of relapse in patients with bulk disease who relapsed after achieving a complete remission with methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (M- or m-BACOD). Eighty-one II, III, or IV patients with disease greater than or equal to 10 cm were identified; 45 of the 81 patients achieved a confirmed complete response (CR) and are included in the analysis. The 45 complete responders included 21 patients with localized (stage II) disease and 24 patients with advanced (stage III/IV) disease. Six of the 21 stage II complete responders and three of the 24 stage II/IV complete responders also received adjuvant radiation therapy following completion of M- or m-BACOD. Only one of the 21 patients with stage II disease relapsed, doing so in the site of prior bulk involvement. In contrast, nine of 24 patients with stage III/IV disease relapsed, although no patient failed solely in the site of prior bulk disease. Stage III/IV patients recurred in either a new site (one patient), a new and old site (five), an old non-bulk site (two), or both old non-bulk and bulk sites (one). These results indicate that advanced-stage bulk-disease patients do not consistently relapse in sites of prior bulk disease; therefore, this group of patients is unlikely to benefit from adjuvant radiation therapy administered following completion of combination chemotherapy. Although the low relapse rate and the addition of adjuvant radiation therapy in a subgroup of the stage II bulk-disease patients precludes a definitive analysis, our results further suggest that these patients may be effectively treated with combination chemotherapy alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Breast carcinoma metastatic to a meningioma. Case report and review of the literature.

We describe a patient who developed an intracranial mass that consisted of a meningioma and metastatic breast cancer. A literature review revealed 12 similar cases. In epidemiologic studies, the incidence of meningioma in patients with breast cancer is higher than expected. Both tumors are more common in women, have been reported to flare during pregnancy, and express hormone receptors. In a patient with breast cancer, an intracranial mass with radiographic features suggestive, but atypical, of a meningioma should be evaluated surgically. The lesion may represent a metastasis, a meningioma, or both.

Bone Neoplasms↗
PubMed1987

The m-BACOD combination chemotherapy regimen in the treatment of diffuse large cell lymphoma.

The m-BACOD regimen attempted to lower the dose of methotrexate in the M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone) program. Between July 1981 and January 1985, 87 previously untreated or minimally treated patients with diffuse large cell lymphoma were treated with the m-BACOD regimen (methotrexate 200 mg/m2 on days 8 and 15, bleomycin 4.0 mg/m2 on day 1, doxorubicin 45 mg/m2 on day 1, cyclophosphamide 600 mg/m2 on day 1, vincristine 1.0 mg/m2 on day 1, and dexamethasone 6 mg/m2 on days 1 to 5; leucovorin was given 24 hours after methotrexate at 10 mg/m2 every six hours for eight doses orally). Of 86 evaluable patients, 59 (68.5%) had a complete remission (CR). Partial response was seen in 21 patients with six still surviving (5 to over 15 months). Of the seven patients who had no change, all have died. The median duration of follow-up for the entire series was 30 months (range, 2 to 61). Relapse from CR occurred in 15 of 59 (25%). Currently, 56 of 87 patients (64%) survive; all but 12 are in their first remission. Overall survival was 84% for those achieving an apparent CR. The major toxic effect of the m-BACOD regimen was myelosuppression with severe leukopenia and fever, which required hospitalization for about 33% of patients. Mucositis occurred in 39 patients; 19 had severe mucositis. No significant difference in overall survival was seen between the high-dose methotrexate M-BACOD and the low-dose m-BACOD regimens.

Adult↗
PubMed1987

Methotrexate-leucovorin factor rescue regimens in diffuse large cell lymphoma.

Early studies of methotrexate (MTX) in non-Hodgkin's lymphoma (NHL) and the rationale for high-dose MTX (HDMTX)-leucovorin (LV) rescue are briefly reviewed. In Phase II studies at the Dana-Farber Cancer Institute, published in 1977, HDMTX-LV (1-7.5 g/m2 MTX) was given to 12 patients with diffuse large cell lymphoma (DLCL) failing prior chemotherapy. Five (24%) patients responded, including 2 with complete remissions (CR). HDMTX, bleomycin, doxorubicin, cyclophosphamide, vincristine and dexamethasone (M-BACOD) was developed (MTX = 3 g/m2 on day 14 of each cycle) in an effort to reduce relapse between cycles of chemotherapy and also to prevent subsequent CNS relapse. Results in 101 patients published in 1983 showed CR in 72% with a projected survival of 59% out to 5 years. For CR patients, survival was 85% with disease-free survival 74%. In order to render the program more feasible, as well as reduce potential toxicity and cost, moderate-dose MTX-LV (200 mg/m2 MTX on day 7 and 14) was substituted for HDMTX-LV. Preliminary results from this new protocol, moderate-dose MTX, bleomycin, doxorubicin, cyclophosphamide, vincristine and dexamethasone (m-BACOD), as of November 1985 in 80 patients, show CR in 60 (75%) patients. The 2-year survival is 70% with a projected 4-year survival of 60%. Review of both protocols shows similar results including rate of CNS relapse (about 5%). In a multivariate analysis, 3 prognostic groups have been defined, which will allow for new therapeutic strategies in future studies. Prospective randomized trials will be required to determine the role, dose, and schedule of MTX-LV in DLCL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Relapse with nodular lymphoma following combination chemotherapy for diffuse non-Hodgkin's lymphoma.

Histologic conversion within the non-Hodgkin's lymphomas is a well-described phenomenon. Conversion from an indolent to that of a more aggressive histologic pattern is the most frequently noted form of this variability. We describe two patients in whom relapse with an indolent nodular lymphoma was noted after combination chemotherapy for diffuse disease. Implications for diagnostic evaluation and therapy as well as the pathogenesis of this unique form of conversion are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Identification of major prognostic subgroups of patients with large-cell lymphoma treated with m-BACOD or M-BACOD.

One hundred twenty-one patients with diffuse large-cell lymphoma treated with m- or M-BACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) were evaluated for pretreatment characteristics predictive for response and survival. Two characteristics, poor performance status and massive bulky disease, were negatively associated with response rate in a multivariate analysis. These two characteristics were also negatively associated with survival in multivariate analysis, as was another factor, an increased number of extranodal sites of disease. These three pretreatment characteristics were used to construct a model containing 12 categories of patients at increasing risk for relapse and shortened survival. These categories divided naturally into three broad groups of patients with respective 5-year survival rates of 68%, 55%, and 24%.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Diffuse aggressive lymphomas: a curable subset of non-Hodgkin's lymphomas.

The diffuse aggressive lymphomas are a major group of non-Hodgkin's lymphomas characterized by diffuse disease, in most cases, and a rapidly progressive clinical course. Until recently, the disease was fatal. Over the last 10 years, use of intermittent high-dose combination chemotherapy with non-cross-resistant drugs has significantly increased the survival time for patients with both local and advanced disease. For those with advanced disease, the most recent studies show complete response rates of 85%, complete-response relapse rates of 10%, and a 73% rate of survival for more than 3 to 5 years. The role of radiation therapy is also important, particularly in the early stages of disease. Salvage treatment with single-agent chemotherapy has achieved often impressive, but brief, responses usually of less than 1 year. Not all patients can tolerate these intensive regimens, however, and new avenues of therapy are being investigated. Various types of biologic response modifiers have been tried in patients who have been heavily pretreated. Monoclonal antibodies initially produced responses in patients with low or intermediate grade tumors, but overall results are still disappointing. Recent trials with interferons show promise especially in patients with low-grade, indolent B cell lymphomas and cutaneous T cell lymphoma. Because antitumor effects are generally of short duration, however, there is probably only a minimal role for biologic therapy in patients with aggressive lymphomas.

Antibodies, Monoclonal↗
PubMed1986

Phase I study of continuous-infusion cisplatin.

Cisplatin was administered to 21 patients as a continuous infusion over 5 days. Doses of 20, 25, and 30 mg/m2/day were studied. When administered in 3 L of normal saline/day, continuous-infusion cisplatin at a dose of 30 mg/m2/day was associated with neuropathy in two of nine patients and creatinine elevations (greater than 2 mg/dl) in four. No neurotoxicity or nephrotoxicity was observed at lower doses. Severe thrombocytopenia (less than 50,000/microliter) was unrelated to dose and occurred in 19% of the courses. Leukopenia was minimal. Nausea and vomiting were easily controlled. No toxicity was seen in 38% of the courses. Nineteen patients were evaluable for response. Six patients achieved partial response (32%), five had minimal response (25%), and eight had progressive disease (42%) in this group. Seven patients had received cisplatin previously as a bolus treatment (20 mg/m2/day for 5 days) and failed on chemotherapy. Among these patients there was one with partial response, three with minimal response, and three with progressive disease. It is concluded that continuous-infusion cisplatin, as given in this protocol, is well-tolerated at a dose of 25 mg/m2/day and can result in responses in patients failing bolus cisplatin at high doses.

Adult↗
PubMed1985

Detection of bone marrow metastasis in small-cell lung cancer by monoclonal antibody.

A murine monoclonal antibody against a surface antigen of small-cell carcinoma of the lung (SM1 antibody) was investigated for its use in detecting bone marrow metastasis. Bone marrow cells of healthy volunteers and of patients with small-cell carcinoma of the lung (SCCL) were examined for reactivity with SM1 antibody and indirect immunofluorescence and the results compared to conventional histochemical staining (Wright-Giemsa stain of bone marrow aspirates and hematoxylin-eosin stains of bone marrow biopsies). No SM1 reactivity was found in marrow cells of eight healthy volunteers. Thirty-six samples from 33 patients with SCCL were examined; tumor involvement was found in 69% by SM1 antibody and in 16% by histochemical stains. All bone marrow samples from patients with SCCL that were unreactive with SM1 antibody also showed no evidence of tumor involvement by histochemical stains. Samples of 29 patients were investigated at initial staging; SM1 reactive cells were found in 50% of 16 patients with limited disease and in 77% of 13 patients with extensive disease. Overall, the proportion of patients recognized to have disseminated disease at diagnosis was increased from 45% to 72% by monoclonal antibody staining. Indirect immunofluorescence with SM1 antibody allows detection of bone marrow metastasis of SCCL that cannot be seen by conventional morphology and can identify disseminated disease in patients otherwise staged limited disease.

Animals↗
PubMed1985

Role of 99mTc methylene diphosphonate bone imaging in the management of lymphoma.

The role of modern techniques of 99mTc methylene diphosphonate bone imaging in the management of lymphoma patients was assessed by comparing results of 107 bone scans in 16 patients with Hodgkin's disease, and 45 patients with non-Hodgkin's lymphoma to simultaneous radiologic, clinical, and histopathologic features as well as to subsequent disease course. The sensitivity and specificity were both greater than or equal to 0.96 in both Hodgkin's disease and non-Hodgkin's lymphoma and the overall accuracy by site was 98%. The scan proved to be useful in the definition and follow-up of skeletal lymphomatous disease in both symptomatic and asymptomatic patients, and defined abnormalities which were not predicted by either serum alkaline phosphatase activity or the presence of bone marrow involvement. In no patient, however, did the bone scan result by itself alter either initial staging or estimates of extent of disease at the time of relapse. Bone scanning, therefore, cannot be recommended as a screening procedure in patients with lymphoma; rather, this test is best reserved for the definition and follow-up of skeletal metastases in patients with active, concomitant, extraosseous disease.

Bone Neoplasms↗
PubMed1984

Autologous bone marrow transplantation following high-dose chemotherapy with cyclophosphamide, BCNU and VP-16 in small cell carcinoma of the lung and a review of current literature.

Four patients with limited disease small cell carcinoma of the lung were treated with high-dose cyclophosphamide (120 mg/kg over days 1 and 2), BCNU (400 mg/m2 over days 1 and 2) and VP-16 (200 mg days 1-5) used as intensification treatment after conventional chemotherapy. To ameliorate hematopoietic toxicity, autologous bone marrow cells collected and cryopreserved prior to treatment were reinfused on day 8. In three patients clinical response was evaluable. Two achieved a complete remission: one died without evidence of tumor after 3 months; the other had a regional relapse after 6 months. One patient who had progression of disease on conventional chemotherapy was refractory to high-dose treatment. Three patients developed diffuse interstitial pneumonitis 3 weeks after treatment and two died of respiratory failure. High-dose intensification chemotherapy with autologous marrow reinfusion may complement the effects of standard combination chemotherapy in small cell carcinoma of the lung. The current status of this approach is reviewed.

Adult↗