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Biomedical subjects

R M Bukowski

Publications and source records attributed to R M Bukowski.

At least 109 records · Page 6Linked to original sources
PubMed1990

Induction by interleukin-2 of oligoclonal expansion of cultured tumor-infiltrating lymphocytes.

To better understand the modulatory effects of interleukin-2 (IL-2) on lymphocyte proliferation, we examined the clonality of the in vitro T-cell response by Southern blot hybridization. Tumor-infiltrating lymphocytes (TILs) grown in the presence of IL-2 for 15-26 days had detectable T-cell receptor beta-chain gene rearrangements, which indicated oligoclonal enhancement in culture in four of nine TIL samples. In contrast, none of 11 uncultured TIL samples had detectable gene rearrangements. Lack of detection in at least three of the five negative, cultured TIL samples could be explained by increased numbers of natural killer cells. We hypothesize that the oligoclonal expansion noted results from the enhanced response of immune-primed T cells to IL-2.

Blotting, Southern↗
PubMed1990

Phase II trial of high-dose intermittent interleukin-2 in metastatic renal cell carcinoma: a Southwest Oncology Group study.

A phase II trial of intermittent high-dose recombinant interleukin-2 (rIL-2) was initiated to evaluate the response rate, remission duration, and toxic effects in patients with measurable metastatic renal cell carcinoma. The rIL-2 was administered as a bolus intravenous infusion at a dose level of 10.0 x 10(6) U/m2 three times weekly, preceded by indomethacin (50 mg orally). Dose reductions of rIL-2 for hypotension and other grade 3 or 4 toxic effects were permitted. Forty-four patients were entered and 41 were eligible. Previous treatment included nephrectomy (23 patients), radiation therapy (seven), and hormone therapy (three). Most toxic effects observed were moderate and included nausea, vomiting, anorexia (85%); hypotension (85%); fever, chills (78%); central nervous system changes (24%); myelosuppression (27%); and creatinine elevation (15%). Four instances of grade 4 toxicity were observed and included nausea, vomiting with dehydration; hypotension; and myocardial infarction. Thirty patients (73%) required dose adjustments because of toxicity. Five responses (12%) were seen, which included one complete and four partial. Sites of response included lung, liver, and soft tissue; the duration of response ranged from 2 to 20+ months. These results demonstrate that this schedule of rIL-2 can be administered in an outpatient setting, and can produce tumor regression in patients with metastatic renal cell carcinoma, including durable complete responses.

Adult↗
PubMed1990

Phase II evaluation of mitoxantrone in advanced pancreatic carcinoma: a Southwest Oncology Group study.

Patient with advanced adenocarcinoma of the pancreas and no prior chemotherapy were treated on a Phase II trial of mitoxantrone. Doses were adjusted for hepatic dysfunction as defined by bilirubin. Twenty-four patients with a bilirubin less than or equal to 1.5 mg% received mitoxantrone 12 mg/m2 i.v. repeated every three weeks. Myelosuppression in the form of leukopenia was the major toxicity. There were no responses in twenty-four evaluable patients.

Adenocarcinoma↗
PubMed1990

Right renal mass with vena caval thrombus.

This case illustrates the difficulties that sometimes occur in the evaluation of patients with a nonfunctioning kidney. Because of the clinical presentation, suggestive of renal cell carcinoma, no urinary cytology study was obtained from the affected kidney. This study certainly would have led to the correct diagnosis. Despite this fact, the operative management would not have changed except for complete removal of the ureter. In our case we elected to follow the distal ureter by ureteral washings and ureteroscopy during follow-up cystoscopy studies to preclude a further operation. Although no data are available on the role of adjuvant therapy in these patients, because of the poor prognosis associated with such extensive disease we gave our patient 2 courses of M-VAC in an attempt to prevent progression of the disease.

Aged↗
PubMed1990

Immunologic studies of alveolar macrophages from patients with metastatic renal cell carcinoma.

Alveolar macrophage function in patients with renal carcinoma, a disease characterized by frequent pulmonary metastases, has not been examined. The purpose of this study was to evaluate tumoricidal responses of alveolar macrophages in renal carcinoma to determine if such activity is compromised. Alveolar macrophages and/or blood monocytes were obtained from 26 normal volunteers and 16 patients with renal carcinoma. Tumoricidal activity of alveolar macrophages and monocytes was assessed against 3H-thymidine-labeled tumor target cells. Patient alveolar macrophages and monocytes exposed to lipopolysaccharide (LPS) or recombinant interferon-gamma expressed tumoricidal activity comparable to those in normal subjects. Activated alveolar macrophages recognized and lysed neoplastic cells (including allogenic renal carcinoma cells), but not nonneoplastic cells. Alveolar macrophage and monocyte tumoricidal responses of patients with pulmonary metastases were not different from those of patients with metastases to other sites. These results indicate that alveolar macrophages from patients with renal carcinoma with or without pulmonary metastases are not compromised in vitro, but respond to immunomodulators with enhanced tumoricidal activity in the same fashion as do alveolar macrophages from normal volunteers.

Adult↗
PubMed1990

Treatment of limited small-cell lung cancer with etoposide and cisplatin alternating with vincristine, doxorubicin, and cyclophosphamide versus concurrent etoposide, vincristine, doxorubicin, and cyclophosphamide and chest radiotherapy: a Southwest Oncology Group Study.

The Goldie-Coldman model explaining the kinetics of tumor cell kill and drug resistance has a potential application in designing chemotherapy regimes. In this Southwest Oncology Group (SWOG) trial we tested the alternation of two potentially noncrossresistant drug combinations with a concurrent drug combination in patients with limited small-cell lung cancer. The concurrent drug combination consisted of etoposide (VP-16), 75 mg/m2/intravenously (IV), days 1, 2, and 3; vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), 40 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (EVAC). The alternating combination consisted of VP-16, 100 mg/m2/IV, days 1, 2, and 3; and cisplatin (CDDP), 100 mg/m2/IV, day 1, alternating with vincristine, 1.0 mg/m2/IV, days 1 and 8; Adriamycin, 50 mg/m2/IV, day 1; and cyclophosphamide, 750 mg/m2/IV, day 1 (VP-16/CDDP-VAC). Chemotherapy was administered at 3-week intervals for six cycles both before and after chest (5,000 rads/5 weeks) and whole brain radiotherapy (3,000 rads/2 weeks). One hundred ninety-nine patients received EVAC and 201 received the alternating combination. There was no significant difference in the response rate to the initial six cycles of treatment with EVAC (CR, 40%) versus the alternating combination (CR, 38%). There was no significant difference between the best response, EVAC (CR, 48%) and VP-16/CDDP-VAC (CR, 51%). Median survival for all randomized patients on EVAC is 15.1 months versus 16.5 months on the alternating combination (P = .58). Toxicities consisted primarily of bone marrow suppression, anorexia, nausea and vomiting, peripheral neuropathies, and alopecia. As in previous trials, the chest was the most common site of relapse (33%). There were no differences in the incidence and sites of relapse between the two treatment arms. These treatments appear equally effective at inducing remission and prolonging survival in patients with small-cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Phase I trial of continuous infusion recombinant interleukin-2 and intermittent recombinant interferon-alpha 2a: clinical effects.

A phase I trial of high-dose continuous infusion rIL-2 over 5 days and i.m. recombinant human interferon-alpha (rHuIFN-alpha 2a) three times weekly in 23 patients with advanced malignancy has been completed. Cohorts of patients were treated at three different dose levels: rIL-2 3.0 x 10(6) u/m2 plus rHuIFN-alpha 2a either 5.0 or 10.0 x 10(6) u/m2, and rIL-2 4.5 x 10(6) u/m2 plus rHuIFN-alpha 2a 5.0 x 10(6) u/m2 over 4 weeks. Dose-limiting toxicity consisted of pulmonary and neurologic side effects, and the maximal tolerated dose was 3.0 x 10(6) u/m2 on days 1-5 or rIL-2, and 10.0 x 10(6) u/m2 three times weekly of rHuIFN-alpha 2a. Four partial responses (renal carcinoma, three; endometrial carcinoma, one) were seen. In conclusion, toxicity of this schedule of rIL-2 and rHuIFN-alpha 2a was significant, but manageable. Further investigation is needed to define the antitumor activity of this combination.

Adult↗
PubMed1990

Phase Ia-Ib trial of an anti-GD3 monoclonal antibody in combination with interferon-alpha in patients with malignant melanoma.

A phase Ia-Ib study was undertaken to treat melanoma patients with a constant dose of the anti-GD3 monoclonal antibody, R24, in combination with increasing dose levels of recombinant interferon-alpha (rHuIFN alpha-2a). Fifteen patients were treated on days 1-5 and 8-12 with a continuous 6-h i.v. infusion of R24 (8 mg/m2) and escalating i.m. doses of rHuIFN alpha-2a. Peripheral blood lymphocytes were obtained at multiple times before and during treatment and monitored for changes in lymphocyte subpopulations and changes in natural killer and antibody-dependent cellular toxicity functional activity. There were no consistent changes in most immune parameters; however, there was a decrease from pretreatment levels in the suppressor T cell (CD8+, CD11b+) subset and a dose-dependent decrease in the helper/inducer (CD4+, Leu-8+) T cell subset. The peak serum concentration of R24 was reached on day 5 of the study and was 9.4 micrograms/ml. During the second week of treatment, peak serum levels of R24 fell to less than 4 micrograms/ml. This finding was related to the development of human antimouse antibody, which would be detected as early as day 8 of the study. Binding of mouse Ig (R24) within the tumor bed was observed in 5 of 12 biopsy specimens. The maximal tolerated dose of the combination was dose level IV, in which patients received 8 mg/m2 of R24 and 50 x 10(6) units of rHuIFN alpha-2a on days 1-5 and 8-12 of treatment.

Adult↗
PubMed1988

Phase II evaluation of sequential hepatic artery infusion of 5-fluorouracil and hepatic irradiation in metastatic colorectal carcinoma.

Twenty-seven patients with measurable liver metastases from colorectal carcinoma were entered on a protocol of intermittent hepatic artery infusion (HAI) of 5-fluorouracil (5-FU) followed by consolidation with hepatic irradiation. Five partial responses were observed in 23 evaluable patients. Median duration of response was 3.5 months. A response was evident after chemotherapy alone in four of five responders. Hepatic irradiation converted one patient with stable disease after chemotherapy to a partial responder. Median survival for all patients was 9.0 months (range 1.5-34.0). Combined modality treatment with HAI of 5-FU followed hepatic irradiation was well tolerated but did not appear to be synergistic.

Colonic Neoplasms↗
PubMed1988

Combination chemotherapy including VP-16 for poor prognosis germ cell neoplasms.

Fifteen patients with germ cell neoplasms (9 testicular primary, 4 extragonadal, 2 adult teratoma syndrome) with features indicative of a poor prognosis were treated with chemotherapy followed by surgery. In patients with testicular primary sites, 2 patients have relapsed and all 9 remain alive (median follow-up 36 months). In patients with extragonadal tumors 2/4 are alive without disease, and both patients with the adult teratoma syndrome have died. Combination chemotherapy and surgery can be employed successfully in this subset of patients with germ cell neoplasms.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Clinical modulation of doxorubicin resistance by the calmodulin-inhibitor, trifluoperazine: a phase I/II trial.

Drug resistance to chemotherapy agents such as doxorubicin appears to be an important cause of therapeutic failure in cancer treatment. Based on preclinical information demonstrating that the phenothiazine calmodulin-inhibitor trifluoperazine can enhance retention and cytotoxicity of doxorubicin in resistant cells, a phase I/II trial of the combination was performed to determine the maximally tolerated dose (MTD) of trifluoperazine that could be administered with doxorubicin. Patients with intrinsic (no previous response) and acquired (previous response with relapse) doxorubicin resistance were eligible. Doxorubicin was administered as a 96-hour continuous infusion (60 mg/m2) on days 2 through 5. Trifluoperazine was administered in divided doses orally on days 1 through 6, with dose escalation from 20 to 100 mg/d. Thirty-six patients were evaluable. The MTD of trifluoperazine was 60 mg/d, with dose-limiting toxicity being extrapyramidal side effects. No alteration of doxorubicin toxicity was observed. Seven of the 36 patients responded (one complete response [CR], six partial responses [PR]), with seven of 21 patients having acquired resistance, and zero of 15 with intrinsic resistance demonstrating responses. Doxorubicin plasma levels were not affected by trifluoperazine, and the maximal trifluoperazine plasma levels achieved were 129.83 ng/mL. This trial demonstrates the combination of trifluoperazine and doxorubicin is well tolerated, and the schedule recommended for phase II trials is doxorubicin, 60 mg/m2 (continuous infusion) days 2 through 5, and trifluoperazine, 15 mg four times per day orally days 1 through 6. Continued investigation of this combination is indicated for patients with acquired doxorubicin resistance.

Adult↗
PubMed1987

A phase II trial of combination chemotherapy in patients with metastatic carcinoid tumors. A Southwest Oncology Group Study.

A prospective Phase II trial of combination chemotherapy in patients with metastatic carcinoid tumors was conducted by the Southwest Oncology Group. The therapy included 5-fluorouracil, Adriamycin, cyclophosphamide, and streptozotocin (FAC-S) or the same combination without Adriamycin (FC-S) in patients with heart disease. Seventy-four patients were entered and two were ineligible. Sixty-nine of the 72 were histologically reviewed. Six patients were declared ineligible after this review. Fifty-six patients received FAC-S, and nine received FC-S (one patient was inevaluable). The response rates were 31% and 22%, respectively. The median survival of all patients was 10.8 months. The analyses of various clinical and histologic parameters indicated that responses were more common in patients with gastrintestinal carcinoids; there was also a tendency toward shorter survival in patients with tumors that had a higher mitotic rate or the atypical and/or undifferentiated histologic pattern. The FAC-S combination can produce objective responses in patients with metastatic carcinoid tumors, but these are generally partial and brief. It was also concluded that currently available chemotherapy is inadequate.

Adult↗
PubMed1987

Clinical trials in colorectal cancer: experience of the Gastrointestinal Tumor Study Group and the Southwest Oncology Group.

Clinical trials in patients with metastatic and locally advanced colorectal carcinoma performed by the Southwest Oncology and Gastrointestinal Tumor Study Groups are reviewed. Therapy of metastatic disease remains unsatisfactory, with new agents and biochemical modulation being studied at present. Adjuvant trials have demonstrated the need for randomization and the inclusion of control groups. Preliminary results are consistent with potential usefulness of a combined modality approach in rectal carcinoma patients (stages B2 and C), with no effects on survival and/or recurrences in colon cancer.

Adjuvants, Immunologic↗
PubMed1987

Phase II trial of sequential chemotherapy and low-dose radiotherapy in advanced gastric adenocarcinoma. A Southwest Oncology Group Pilot Study.

Thirty-four patients with metastatic gastric adenocarcinoma were treated with the combination of chemotherapy and radiation therapy in a Phase II trial. Induction chemotherapy consisted of one cycle of 5-fluorouracil (5-FU), adriamycin, and BCNU (FAB), followed in 4 weeks by a cycle of 5-FU, adriamycin and mitomycin-C (FAM). In responding and stable patients, consolidation radiotherapy to major sites of disease, followed by maintenance FAM, was administered. Twelve of 30 (40%) patients with measurable disease responded (3 complete responses and 9 partial responses), with a median response duration of 6.0 months. Toxicity was moderate and consisted of nausea, vomiting, and myelosuppression. No additive effects for this combined modality approach could be demonstrated.

Adenocarcinoma↗
PubMed1987

5-Fluorouracil and folinic acid in the treatment of metastatic colorectal cancer: a randomized comparison. A Southwest Oncology Group Study.

In order to determine the clinical applicability of the in vitro observation of enhanced cytotoxicity of 5-fluorouracil (5-FU) in the presence of excess reduced folates, the Southwest Oncology Group (SWOG) performed a randomized trial evaluating two dose schedules of 5-FU and folinic acid (FA) in 128 patients with metastatic colorectal cancer. Of 125 eligible patients, 62 were randomized to receive bolus FA (200 mg/m2 days 1 through 4) in addition to 5-FU (1,000 mg/m2 days 1 through 4) by continuous four-day infusion (infusion arm), while 63 were randomized to receive bolus FA (200 mg/m2 days 1 through 5) in addition to 5-FU (325 mg/m2 days 1 through 5) by bolus injection (bolus arm). The toxicities of the two schedules differed, with stomatitis being more severe in the infusion arm and leukopenia being more severe in the bolus arm. The response rates and survival data for the two arms are nearly identical. The median survival of patients on the infusion arm is 11.0 months and of patients on the bolus arm, 10.3 months. The infusion arm produced one complete response (CR) and 12 partial responses (PRs), for a major response rate of 21% of eligible patients. The bolus arm produced three CRs and 11 PRs, for a major response rate of 22% of eligible patients. The response rate produced is minimally superior to recent cooperative group studies of colorectal cancer, but the response rate and survival experience are within the range of experience for treatment with 5-FU alone.

Adenocarcinoma↗