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Biomedical subjects

P Wiernik

Publications and source records attributed to P Wiernik.

17 recordsLinked to original sources

Non-hodgkin malignant lymphoma with tissue neutrophilia: a report of 3 cases.

CONTEXT: Neutrophils, in the absence of necrosis, are uncommon in non-Hodgkin malignant lymphoma. Recently, a neutrophil-rich type of Ki-1 (CD30)-positive, anaplastic large cell lymphoma was described. OBJECTIVES: We report 3 cases of nonanaplastic large cell lymphoma with an abundance of tissue neutrophils; 2 cases were associated with breast carcinoma and possible infection. RESULTS: Peripheral blood neutrophilia was noted in only 1 of these 3 patients. Neutrophilia in the lymph nodes occurred in either a sinusoidal or interstitial pattern. Multiple biopsies were available for review in 2 patients; however, tissue neutrophilia was present in only 1 biopsy each. CONCLUSION: These findings suggest that nonanaplastic large cell lymphoma-related tissue neutrophilia is a transient phenomenon.

Aged↗

Epirubicin has modest single-agent activity in head and neck cancer but limited activity in metastatic melanoma and colorectal cancer: phase II studies by the Eastern Cooperative Oncology Group.

Epirubicin (4'-epidoxorubicin), a diastereoisomer of doxorubicin, has established activity in the treatment of many cancer types sensitive to doxorubicin. Its activity in other tumor targets such as melanoma, head and neck cancer, and recurrent colorectal cancer has been less well defined. Three concurrent phase II studies examined the efficacy and toxicity of epirubicin (90 mg/m2 given intravenously at 3-week intervals) in the treatment of 71 patients with the aforementioned cancers. Of 66 eligible patients who were assessable for response, one patient (with colorectal cancer) achieved a complete response and three patients (with head and neck cancer) achieved partial responses. The response rate in patients with head and neck cancer was 18% (95% confidence interval, 4-43%). Myelosuppression, alopecia, and nausea were the most frequent toxicities. Two patients died of neutropenic sepsis and grade IV leukopenia occurred in six patients (8%). Grade III toxicities were as follows: leukopenia (17%), anemia (10%), alopecia (8%), fever (1%), thrombocytopenia (1%). Grade I or II cardiac toxicity was noted in four patients at cumulative doses ranging between 375 mg/m2 to 1,283 mg/m2. Epirubicin is ineffective as a single agent at this dose and schedule in the treatment of patients with melanoma and colorectal cancer. In head and neck cancer, a modest response rate encourages further exploration of epirubicin and related anthracyclines in combination regimens.

Adult↗

Meta-analysis of chemotherapy versus combined modality treatment trials in Hodgkin's disease. International Database on Hodgkin's Disease Overview Study Group.

DESIGN: To perform a meta-analysis of all randomized trials that compared chemotherapy (CT) alone versus combined modality treatment (CT + radiotherapy [RT]) for which individual patient data could be made available. PATIENTS AND METHODS: Data on 1,740 patients treated on 14 different trials that included 16 relevant comparisons have been analysed. Eight comparisons were designed to evaluate the benefit of additional RT after the same CT (CT1 v CT1 + RT; additional RT design). Eight comparisons were designed to evaluate whether RT in a combined modality setting can be substituted by CT using either more cycles of the same CT or regimens that contain additional drugs (CT1 + CT2 v CT1 + RT or CT1 v CT2 + RT; parallel RT/CT design). RESULTS: Additional RT showed an 11% overall improvement in tumor control rate after 10 years (P = .0001; 95% confidence interval [CI], 4% to 18%). No difference could be detected with respect to overall survival (P = .57; 95% CI, -10% to 4%). In contrast, when combined modality treatment was compared with CT alone in the parallel-design trials, no difference could be detected in tumor control rates (P = .43; 95% CI, -6% to 9%), but overall survival was significantly better after 10 years in the group that did not receive RT (P = .045; 8% difference; 95% CI, 1% to 15%). There were significantly fewer fatal events among patients in continuous complete remission (relative risk [RR], 1.73; 95% CI, 1.17 to 2.53; P = .005) if no RT was given. CONCLUSION: Combined modality treatment in patients with advanced-stage Hodgkin's disease overall has a significantly inferior long-term survival outcome than CT alone if CT is given over an appropriate number of cycles. The role of RT in this setting is limited to specific indications.

Antineoplastic Agents↗

Long-term follow-up of three randomized trials comparing idarubicin and daunorubicin as induction therapies for patients with untreated acute myeloid leukemia.

BACKGROUND: Most clinical trials for acute leukemia have reported results after 2-3 years of follow-up. Comparisons between the original data and longer-term follow-up data may be of interest, particularly with regard to promising new therapies. METHODS: In 1996, survival data were updated from three prospective, randomized comparisons of idarubicin and daunorubicin that began in 1984 and 1985. These were trials of the Memorial Sloan-Kettering Cancer Center (MSKCC), the U.S. Multicenter Study Group, and the Southeastern Cancer Study Group (SEG). The original results of these trials were reported in 1991 and 1992. RESULTS: The original results of the SEG trial demonstrated no significant difference between idarubicin and daunorubicin. The updated survival analysis showed similar results. The MSKCC trial revealed a significant advantage of idarubicin compared with daunorubicin in both the original and the updated analyses. The U.S. Multicenter trial found a significant difference favoring idarubicin in the original analysis, but the difference was not significant in the updated analysis. CONCLUSIONS: It is essential that the median length of follow-up be clearly stated in any clinical trial. When the results obtained with a particularly promising new drug or procedure are presented early in the course of study (within 1-2 years), the investigators should strongly consider a repeat evaluation after an additional 3-5 years of follow-up.

Acute Disease↗

Randomized multicenter trial of cytosine arabinoside with mitoxantrone or daunorubicin in previously untreated adult patients with acute nonlymphocytic leukemia (ANLL). Lederle Cooperative Group.

This phase III, randomized trial in previously untreated adults with ANLL compared mitoxantrone plus cytosine arabinoside with the CALGB "7 + 3" daunorubicin-based regimen. Two hundred evaluable patients (98 treated with the mitoxantrone-based regimen and 102 with the daunorubicin-based regimen) were included in the analysis of efficacy. The median age of the patients was 60 years. The induction regimen comprised cytosine arabinoside 100 mg/m2 by infusion daily for 7 days and mitoxantrone 12 mg/m2 or daunorubicin 45 mg/m2 daily for days 1-3. If needed, a second induction course was administered: cytosine arabinoside for 5 days and mitoxantrone or daunorubicin for 2 days. Postremission therapy consisted of two consolidation courses, identical to the second induction course. Sixty-three percent (62 of 98) of patients treated with mitoxantrone achieved complete remission (CR), compared to 53% (54 of 102) treated with daunorubicin. The median time to CR was 35 days in patients treated with mitoxantrone and 43 days for those treated with daunorubicin. Eighty-nine percent (55 of 62) of patients treated with mitoxantrone who entered complete remission achieved CR following one induction course, compared to 68% (37 of 54) of patients treated with daunorubicin who entered CR. The median duration of CR was 240 days in patients treated with mitoxantrone and 198 days in those treated with daunorubicin; the median length of survival was 328 days in patients who received mitoxantrone and 247 days in those who received daunorubicin. The toxicity profiles in patients treated with either of the two regimens were comparable in incidence and in severity. Patients treated with mitoxantrone required fewer median platelet units and were treated with fewer median days of intravenous antibiotics, compared to those who received daunorubicin. Mitoxantrone in combination with cytosine arabinoside is effective in previously untreated ANLL. complete remissions occur more frequently after a single induction course of the mitoxantrone-based regimen, compared to the standard Cancer and Acute Leukemia Group B regimen. This should be explored in further trials.

Adult↗

Taxol produces a predominantly sensory neuropathy.

Taxol, a plant alkaloid with promise as an antineoplastic agent, produced a predominantly sensory neuropathy in 16 of 60 patients treated in two phase I trials. This neuropathy occurred only at taxol doses greater than 200 mg/m2. Symptoms typically started 1 to 3 days following treatment, beginning in the hands and feet simultaneously in most patients. Electrophysiologic data suggests both axonal degeneration and demyelination. This previously undefined neurotoxic neuropathy most likely results from taxol's unique ability to produce microtubule aggregation in dorsal root ganglion cells, axons, and Schwann cells.

Adult↗

Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. A phase II clinical trial.

STUDY OBJECTIVE: To confirm the antitumor efficacy of treatment with interleukin-2 and lymphokine-activated killer cells in patients with metastatic renal cancer. DESIGN: Nonrandomized, phase II clinical trial. SETTING: Tertiary care units in university medical centers. PATIENTS: Consecutive trial of 35 patients with metastatic or unresectable renal cell cancer who have bidimensionally measurable disease, performance status 0 or 1, and normal function of all vital organs. Thirty-two patients completed interleukin-2 priming and received at least one lymphokine-activated killer cell infusion. Three patients were removed from the study and did not receive infusion of cells secondary to rapid tumor progression or toxicity. INTERVENTIONS: Patients initially received recombinant interleukin-2, 100,000 units/kg body weight every 8 hours, on days 1 to 5 in a priming phase to stimulate lymphokine-activated killer cell precursors and effector activity in vivo. Leukapheresis was done on days 8 to 12 and lymphocytes were cultured in vitro with interleukin-2 for 3 to 4 days to amplify lymphokine-activated killer cell activity. Finally, interleukin-2, 100,000 units/kg every 8 hours, was infused with cultured cells on days 12 to 16. All doses of interleukin-2 and lymphokine-activated killer cells were administered in intensive care units. MEASUREMENTS AND MAIN RESULTS: The mean number of doses of interleukin-2 administered during the priming phase was 12.9 +/- 0.4; the mean number of lymphokine-activated killer cells reinfused was 7.0 +/- 0.6 X 10(10); and the mean number of interleukin-2 doses administered during the last phase was 10.2 +/- 0.6. The overall objective response rate was 16%; two patients had complete responses and three patients had partial responses with greater than 50% reduction of all measurable tumor. The complete responders remain disease-free at 12 and 9 months. Two partial responders have not had tumor regrowth at 16 and 15 months. The third partial responder relapsed at 4 months. Toxicity was severe but generally of short duration and manageable. There were no treatment-related deaths. Hypotension, weight gain, anemia, and elevations of serum creatinine levels and liver enzymes were common. Two patients required intubation; one patient had a myocardial infarction. CONCLUSIONS: This phase II study confirms the antitumor activity of interleukin-2 and lymphokine-activated killer cell therapy in patients with metastatic or unresectable renal cell cancer. Response rates, especially complete remission rates, are comparable or better than rates achieved with other forms of therapy.

Adult↗

Volume determinations in computed tomography.

Modern computed tomographic (CT) scanners allow reasonably high-resolution cross-sectional visualization of most viscera and masses. To determine the accuracy of CT volume estimation, CT volumes of inanimate objects, cadaver kidneys and spleens, and in vivo balloons were performed. Regions of interest were outlined by a hand-operated cursor, and the computer program calculated the cross-sectional area in square millimeters and in pixels. A second computer program used Simpson's rule to calculate the volume from these multiple cross-sectional area. Calculated CT volumes were within +/-10% of directly measured volumes. Tumor masses being treated by chemotherapy were followed up clinically and by CT. Volume changes determined by CT are believed to be equal to and frequently more sensitive than clinical examination. From our experimental CT and clinical experiences, accuracy can be affected by (1) respiratory movement; (2) rapid changes in in vivo blood volume; (3) low CT number-gradient at the objects' periphery; (4) observer error in cursor tracing of the desired structure; and (5) mathematical errors inherent in Simpson's rule. We conclude that CT can estimate volumes of CT definable masses and can be useful in following tumor response to therapy.

Female↗

Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study.

A randomized comparison of the relative efficacy and toxicity of daunorubicin (DNR) at 30 or 45 mg/sq m or adriamycin (ADM) at 30 mg/sq m, given on the first 3 days of a 7-day continuous infusion of cytosine arabinoside (ara-C) at 100 mg/sq m/day, shows the outcome to be dependent on anthracycline, dose, and patient age. DNR 45 is significantly better than DNR 30 or ADM 30 for inducing complete remissions (CR) in patients younger than 60 yr, (72%, 59%, 58% CRs, respectively). DNR 30 is better than DNR 45 or ADM 30 for inducing CR in patients older than 60 yr (47%, 31%, 35%, respectively). There was a corresponding shift in the induction mortality for the age, dose, and anthracycline groups. Adriamycin was significantly more toxic to the gastrointestinal tract than daunorubicin. The duration of complete remission, with cyclic courses of maintenance therapy, was independent of the patient's age, the dose, or choice of anthracycline used in induction, and of whether the maintenance courses were given every 4 wk or every 8 wk.

Adolescent↗

Dose and treatment factors in radiation-related pericardial effusion associated with the mantle technique for Hodgkin's disease.

A retrospective study of 83 patients with Stage I-III Hodgkin's disease treated with an upper mantle field revealed a rate of radiation-related pericardial effusion (RRP) of 28.9% (24/83). Clinical presentation was asymptomatic effusion in 10/24 and symptomatic effusion in 14/24. RRP was self-limited in all but 4 patients, who progressed to chronic effusion requiring pericardiectomy (4/24). A midplane mediastinal dose of 4000 rads in 4 weeks was given with an anteriorly weighted mantle field that resulted in an average pericardial dose of 5325 rads (1823 ret) and an average midplane cardiac dose of 4625 rads (1558 ret). The rate of RRP was correlated with increasing degree of mediastinal Hodgkin's disease. Increased incidence of RRP with increasing cardiac and pericardial dose could not be proven statistically. Factors which may facilitate pericardial effusion following a basic radiation injury are discussed.

Hodgkin Disease↗

Use of the computed tomographic whole body scanner to stage and follow patients with advanced ovarian carcinoma.

Advanced ovarian carcinoma continues to be a difficult tumor to evaluate noninvasively. Recent developments in chemotherapy have enhanced response rates in this disease, thus improving the likelihood of tumor regression. Computed Tomography (CT) allows the noninvasive estimation of tumor extent in patients with ovarian carcinoma. Seventeen patients with epithelial ovarian carcinoma had 22 whole body CT scans performed either just prior to or following laparotomy. For determination of tumor involvement, when the CT was positive, a high pathologic correlation was found at liver, ascitic, peritoneal, mesenteric, and omental sites (sensitivity). When the cT was negative, high pathologic correlation was found at ascitic and mesenteric sites (specificity). Lower and negative correlation at other disease sites is attributed to difficulty of CT detection of small (1 cm) tumor nodules on visceral surfaces. Eighteen patients with advanced ovarian carcinoma were followed prospectively during treatment with repetitive CT scans. CT results were compared with physical examination, other radiologic studies, and clinical status. In 83% (15/18) of patients and 88% (59/67) of CT scans performed, CT was found to contribute useful management information. Clinical decisions were made on the basis of CT alone in 43% (29/67) of scans performed. These data suggest that CT scanning is very useful in the staging and follow-up of patients with ovarian carcinoma and can replace other radiologic procedures, but it is not completely accurate and needs to be correlated with physical examination and in cases without tumors visible with CT, with laparotomy.

Female↗

Meningeal carcinomatosis from small cell carcinoma of the lung. Consequence of improved survival.

The cells of oat cell carcinoma of the lung can be identified in sputum because of their characteristic morphologic appearance. The cells from oat cell carcinomas can also be identified in other body fluids but are seen there less often. Spinal fluid involvement with oat cell carcinoma has been seen very infrequently, presumably because of a poor survival rate. Aggressive systemic chemotherapy has improved survival, and meningeal involvement is now being recognized as a complication. Of 62 patients treated by aggressive chemotherapy protocols, six (10%) were found to have leptomeningeal involvement by cytologic evaluation of cerebrospinal fluid (CSF). Involvement was found 6 to 13 months after the initiation of therapy. Two of the six patients had no evidence of CNS metastases by CAT brain scan. Necropsy was performed in three of the six cases and showed excellent histologic correlation with the cytologic findings. Because of most therapeutic drugs' poor penetration into the CSF, and because the spinal cord is not routinely irradiated, cytologic examination of the CSF from patients with oat cell carcinoma is necessary when there are new neurologic signs or symptoms to ensure proper, specific therapy.

Carcinoma, Small Cell↗