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Biomedical subjects

J D Bitran

Publications and source records attributed to J D Bitran.

At least 19 recordsLinked to original sources
PubMed1992

In-vitro resistance to zidovudine and alpha-interferon in HIV-1 isolates from patients: correlations with treatment duration and response.

OBJECTIVE: To measure in-vitro antiviral drug susceptibilities of human immunodeficiency virus type 1 (HIV-1) isolates recovered from patients treated with alpha-interferon or zidovudine and patients not treated with these drugs and to examine the relation of these susceptibility measurements to duration of therapy, disease stage, and response to alpha-interferon therapy. DESIGN: Cross-sectional study. SETTING: Outpatient HIV clinic. PATIENTS: Twenty-six ambulatory HIV-1-infected patients: Fifteen of these patients were receiving alpha-interferon therapy, and 11 had never received such therapy. Nine patients were participating in a clinical trial of combination therapy with zidovudine and alpha-interferon. MEASUREMENTS: The 50% inhibitory concentration (IC50) of zidovudine and alpha-interferon was determined for HIV-1 isolates recovered from each patient. Plasma concentrations of HIV-1 p24 antigen in the nine patients in the clinical trial were measured monthly after alpha-interferon was added to zidovudine monotherapy. RESULTS: Zidovudine IC50 (range, 0.01 to 4.87 microM) increased steadily with duration of zidovudine therapy (r = 0.57, P = 0.003). In contrast, alpha-interferon IC50 (range, 0.8 to 415 units/mL) was not related to duration of alpha-interferon treatment; in fact, high IC50s were found in isolates from patients who had never received exogenous alpha-interferon therapy. Resistance to alpha-interferon was greater in isolates from the 15 patients with the acquired immunodeficiency syndrome (AIDS) (median, 104 units/mL) than in those from the 10 patients without AIDS (median, 50 units/mL). Interferson activity was detected in plasma samples from 23 of 24 patients and was also at higher levels in patients with AIDS than in HIV-infected patients without AIDS. Reductions in plasma concentrations of HIV-1 p24 antigen in nine patients after beginning alpha-interferon therapy were greater in those with more susceptible isolates (r = -0.72, P = 0.03). CONCLUSIONS: Interferon resistance, possibly due to endogenous interferon, is not related to duration of interferon therapy but may limit the effectiveness of interferon therapy. Determinations of interferon susceptibility may identify patients most likely to benefit from this agent.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Zidovudine-interferon-alpha combination therapy in patients with advanced human immunodeficiency virus type 1 infection: biphasic response of p24 antigen and quantitative polymerase chain reaction.

In an open-label dose-ranging pilot trial, 13 homosexual men with human immunodeficiency virus type 1 (HIV-1) p24 antigenemia after at least 6 weeks of zidovudine monotherapy were continued on zidovudine and given interferon-alpha, 1.25-7.5 x 10(6) units/m2 subcutaneously three times/week. Plasma p24 antigen levels demonstrated a biphasic response, falling initially in 11 patients by a mean of 50% (95% confidence interval, 36%-64%; P = .001) at a median of 11 weeks, but rising steadily thereafter (P = .001). CD4+ cell counts fell by a mean of 7.1 cells/mm3/week (P = .01). Higher initial CD4+ counts predicted greater p24 antigen reductions. At higher interferon doses no greater reductions in p24 antigen occurred, but side effects were more severe and CD4+ lymphocyte counts fell faster. Polymerase chain reaction quantification of HIV-1 DNA in 3 patients showed a biphasic pattern paralleling the p24 antigen response. In sum, although evidence of short-term effects was found, the combination showed no evidence of lasting antiviral activity beyond that achieved with zidovudine alone in patients with advanced HIV-1 infection.

AIDS-Related Complex↗
PubMed1992

Treatment and prognosis of orbital non-Hodgkin's lymphomas.

Twenty patients with orbital lymphomas were treated and followed over a 14-year period. Ten of these patients had well-differentiated lymphocytic lymphoma (WDL), and all of them were clinical stage IE. Five patients had nodular poorly differentiated lymphocytic lymphomas (NPDL), three patients had diffuse histiocytic lymphomas (DHL), one had nodular mixed-cell lymphoma, and one had diffused mixed-cell lymphoma. The patients with WDL received local radiation therapy, and all of them entered completed remissions. The projected survival at 10 years was 100% for these patients. The patients with low-grade lymphomas with advanced disease were treated with chlorambucil and prednisone or cytoxan and vincristine. The patients with high-grade lymphomas received treatment with methotrexate, cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone (mBACOD) or cyclophosphamide, vincristine, methotrexate, cytosine arabinoside, leucovorin (COMLA). The overall survival estimate for all patients was 63% at 10 years. The disease-free survival was 49% at 10 years. The patients with high-grade lymphomas had a poor prognosis, with no survivors after 4 years. This study suggests that patients with WDL usually present with localized disease to the involved orbit, and have an excellent prognosis with radiation therapy alone. Patients with high-grade orbital non-Hodgkin's lymphomas have a poor outcome despite use of aggressive combination chemotherapy regimens.

Aged↗
PubMed1992

The impact on survival by adjuvant chemotherapy and radiation therapy in stage II non-small-cell lung cancer.

Forty-nine consecutive patients with pathologic Stage II non-small-cell lung cancer treated over a 15-year period were retrospectively reviewed. The treatment strategy evolved during the period of review. Early patients were treated with surgery alone (S); subsequent patients were treated with adjuvant radiation therapy (SR); and more recent patients were treated with postoperative chemotherapy and radiation therapy (SRC). Fifteen patients received S alone, 10 patients received SR, and 24 patients received SRC. The median survival time (MST) of all 49 patients was 20 months, and the estimated 5-year survival was 25%. The MST of patients in each of the three treatment arms was S-6 months; SR-19 months; and SRC-25 months. The majority of patients died from systemic relapses or second primary lung cancers. The addition of adjuvant therapy (SR, SRC) significantly improved the MST of patients compared to surgery alone (S). The overall survival of patients did not change between treatment arms.

Adult↗
PubMed1992

High-dose consolidation therapy with autologous stem-cell rescue in stage IV breast cancer: follow-up report.

PURPOSE: Fifty-nine patients with newly diagnosed metastatic breast cancer were treated with induction chemotherapy followed by high-dose intensification and autologous stem-cell rescue (ASCR) to determine therapeutic efficacy. PATIENTS AND METHODS: Induction consisted of cyclophosphamide, doxorubicin, vincristine, and methotrexate with leucovorin rescue (LOMAC) in 27 patients, or fluorouracil, cisplatin, doxorubicin, and cyclophosphamide (FCAP) in 32 patients. Intensification after LOMAC was cyclophosphamide and thiotepa (CyTepa) with ASCR, and after FCAP it was cyclophosphamide, thiotepa, and carmustine (BCNU) in all but eight patients who received CyTepa. RESULTS: Median survival from study entry for the entire group was 13.3 months. Median time to progression from reinfusion for the 45 patients who underwent intensification was 7.5 months. After LOMAC and intensification, there were 12 complete responses (CR) (nine partial responses [PRs] after induction converted to CRs). Responses after FCAP and intensification were eight CRs (two PRs after induction converted to CRs). Median time to treatment failure from reinfusion was 5.4 months for LOMAC and intensification, and was 10.5 months for FCAP and intensification. Median survival from study entry was 15.1 months for all 27 LOMAC patients and 9.3 months for all 32 FCAP patients. Median time to treatment failure from reinfusion for 11 patients who were CRs at intensification has not been reached and is more than 13 months compared with a median of 5.5 months for the 23 patients in partial remission at intensification. CONCLUSIONS: High-dose intensification therapy has led to increased CR rates in metastatic breast cancer. The role of such therapy in the treatment of stage IV breast cancer requires further refinement.

Adult↗
PubMed1992

Malignancies of undetermined primary origin.

Unknown primary malignancy (UPM) is not a disease entity. Rather, it represents a variety of different metastatic, malignant neoplasms all presenting with either an occult primary or having such a highly undifferentiated histologic appearance that an accurate pathologic classification on routine hematoxylin-eosin section is not possible. UPM is a spectrum of malignancies that includes those that are treatable and curable and those for which no specific treatment exists. For the physician, a diagnosis of UPM represents a beginning rather than an end. The minimal workup of such patients includes a thorough history and physical examination, complete blood counts, urine analysis, multichannel chemistries, a chest radiograph, and computed tomography of the abdomen and pelvis. Having completed this workup, further tests are unnecessary and unwarranted unless specific symptoms or physical signs exist. Once the aforementioned workup is completed, the physician must communicate frequently and freely with the pathologist as further diagnostic tests will be laboratory based and include electron microscopy, histochemical stains, and immunocytochemistries. Immunocytochemistries are relatively new laboratory procedures which have made a significant contribution in the accurate pathologic diagnosis of a tissue specimen that in years past would have been classified as an unidentified malignant neoplasm. An initial panel of immunocytochemistries (vimentin, cytokeratin, CEA, and common leukocyte antigen) should be performed on the tissue block in patients with UPM as they provide direction in the accurate classification of the malignant neoplasm. Chromosomal analysis of tissue is useful in the recognition of lymphomas or soft-tissue sarcomas which would otherwise be classified as UPM. In years to come, when specific DNA probes capable of identifying specific chromosomal rearrangeaments are widely available, pathologic classification of UPM will be performed on a molecular level. Some unknown primary malignancies are treatable and potentially curable. These include large cell lymphoma, extragonadal germ cell malignancies, squamous cell carcinoma metastatic to cervical lymph nodes without an obvious primary, metastatic adenocarcinoma to axillary lymph nodes in women (invariably on occult breast primary), and malignant ascites in women, which usually represents ovarian cancer. Metastatic adenocarcinoma of unknown primary origin, with the exception noted above and the rare presentation of an occult prostate cancer as UPM, is an ultimately fatal malignancy with a relatively shor clinical course.(ABSTRACT TRUNCATED AT 400 WORDS)

Biomarkers, Tumor↗
PubMed1991

Etoposide and mitomycin in the treatment of non-small-cell lung cancer. A phase I-II evaluation.

Sixty-five patients (20 patients who had had prior radiotherapy and 45 patients who had not had prior radiotherapy) were entered into a study evaluating escalating doses of etoposide and mitomycin in the treatment of non-small-cell lung cancer (NSCLC). Twenty-two percent of patients who had not received prior radiotherapy responded to the chemotherapy, compared with 5% of patients who had received prior radiotherapy. The best response rate and median survival time was 30% and 31.9 weeks, respectively, seen in three of 10 patients receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M2 i.v. days 1-3. The major toxicity was hematologic--mainly leukopenia, in 59% of patients who had had no prior radiation therapy and were receiving mitomycin 10 mg/M2 i.v. day 1 and etoposide 150 mg/M2 i.v. days 1-3 (grade 3 and 4 hematologic toxicity). The mitomycin-etoposide drug combination has some activity in patients with NSCLC who have not received prior radiotherapy. The recommended starting dose is mitomycin 10 mg/M2 i.v. day 1 and etoposide 100 mg/M2 i.v. days 1-3, administered every 4 weeks.

Adenocarcinoma↗
PubMed1990

High-dose tri-alkylator chemotherapy with autologous stem cell rescue in patients with refractory malignancies.

Forty patients with refractory solid tumors or non-Hodgkin's lymphoma were treated with high-dose cyclophosphamide, thiotepa, and carmustine (BCNU), followed by autologous stem cell rescue, in a phase I dose escalation study. The dose-limiting toxic effect was delayed drug-induced pulmonary disease, seen in three patients who received 660-750 mg of BCNU/m2 in combination with cyclophosphamide and thiotepa. The early death rate due to toxic effects was 20%; all deaths were attributed to sepsis or respiratory failure. The overall response rate was 63%. The median time to disease progression was 14 weeks. Although this regimen provided effective cytoreduction, its use in heavily pretreated patients with bulky disease is of limited value.

Adult↗
PubMed1990

Chemotherapy for stage IV non-small cell lung cancer.

Chemotherapy regimens with consistent activities in NSCLC have been identified. A modest but statistically significant increase in survival has been shown in a single large randomized trial, with three smaller trials showing either similar results or a trend toward an improved survival. However, chemotherapy-related toxicity remains significant and seems exacerbated in patients with a poor performance status at the time of diagnosis. Identification of chemotherapy regimens with higher activity in NSCLC remains a necessity, and the treatment of stage IV patients on clinical trials should be encouraged. Outside the context of a clinical trial, chemotherapy is indicated in selected stage IV patients with good performance status in an attempt to palliate their symptoms and increase their survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Supportive care of the lung cancer patients.

The care of lung cancer patients involves a specialized team approach. Complications arising from the underlying illness or its treatment are common occurrences that must be anticipated and treated properly. Psychosocial issues commonly arise in patients and their families during the course of the illness. Caregivers skilled in helping a patient and family members come to terms with this frequently fatal disease are integral members of a multidisciplinary team of cancer specialists.

Analgesics↗
PubMed1990

Peripheral blood-derived stem cell collections for use in autologous transplantation after high dose chemotherapy: an alternative approach.

Peripheral blood-derived hematopoietic stem cells (PBHSC) can be utilized to reconstitute hematopoiesis in patients after high dose myeloablative chemotherapy. We have performed PBHSC reinfusion in 18 patients who have or had a history of tumor involving the bone marrow or a hypocellular bone marrow. The PBHSC were collected by continuous flow leukapheresis and subsequently cryopreserved. A median of 31.9 X 10(9) (range 18 X 10(9)-67.2 X 10(9)) mononuclear cells or a median of 4.85 X 10(8) mononuclear cells/kg (range 2.7 X 10(8)-11.0 X 10(8)) were collected. Fifteen patients had in vitro assays of granulocyte-monocyte colony-forming cells (CFU-GM) performed with a median of 2.7 X 10(4) (range 0-11.5 X 10(4)) CFU-GM/kg. To date, of the 18 patients collected, all have undergone high dose chemotherapy and PBHSC reinfusion. For the evaluable patients, granulocyte recovery (greater than 500 X 10(6)/ml) has occurred in a median of 15 days and platelet recovery (greater than 50 X 10(9)/ml without transfusion support) has occurred in a median of 43 days. Four patients have had prolonged thrombocytopenia and still require platelet transfusion at 80+, 97+, 124+, and 270+ days. PBHSC collection is safe and effective for hematopoietic reconstitution after high dose chemotherapy in the majority of patients; however incomplete hematopoietic reconstitution has been observed in 4/18 evaluable patients. This procedure requires further investigation.

Adult↗
PubMed1990

A phase I-II study of high-dose cyclophosphamide, thiotepa and escalating doses of mitoxantrone with autologous stem cell rescue in patients with refractory malignancies.

Twenty-five patients with refractory solid tumors were treated with high-dose cyclophosphamide, thiotepa and mitoxantrone followed by autologous stem cell rescue in a phase I dose escalation study. The dose-limiting toxic effect was mucositis at 60 mg/m2 of mitoxantrone in combination with cyclophosphamide and thiotepa. The early death rate due to toxic effects was 24%; all deaths were attributed to infections. Hematopoietic recovery was quite prolonged with median times to granulocyte (greater than 500 x 10(6)/l) and platelet (greater than 50 x 10(9)/l) recovery at 58 and 148 days, respectively. The overall response rate was 56%. The median time to progression was 14 weeks. Thus, this regimen has activity against refractory malignancies although early and prohibitive toxicity occurs when mitoxantrone is escalated in this setting.

Actuarial Analysis↗