Interferon-gamma and CXC chemokine induction by interleukin 12 in renal cell carcinoma.

Interleukin 12 (IL-12) is known to play an important role in the development of an antitumor response. Its activity has been shown to be dependent upon the intermediate production of IFN-gamma and the influx into the tumor of CD8 lymphocytes. In a murine model, tumor regression induced by IL-12 treatment correlated with IFN-gamma, IP-10, and Mig expression in the tumor bed and was abrogated by antibodies to both chemokines.

Phase I/II trial of human recombinant granulocyte-colony-stimulating factor (filgrastim) and escalating doses of cyclophosphamide, mitoxantrone, and 5-FU in the treatment of advanced breast cancer.

Purpose: We performed a phase I/II dose-escalation trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) in combination with human recombinant granulocyte-colony-stimulating factor (G-CSF, filgrastim) in patients with advanced breast cancer. The objectives of this trial were (1) to gain experience with filgrastim given to patients with advanced breast cancer and receiving standard-dose CNF, and (2) to determine the maximum tolerated dose of CNF that could be given with filgrastim support by incremental dose escalation of two components of the CNF regimen, cyclophosphamide and mitoxantrone.

Methods: Four patients who had received prior therapy for advanced disease received standard-dose CNF with filgrastim support.

Mature results from a phase II trial of accelerated induction chemoradiotherapy and surgery for poor prognosis stage III non-small-cell lung cancer.

Mature results are reported from a phase II trial of accelerated induction chemoradiotherapy and surgical resection for stage III non-small-cell lung cancer whose prognosis is poor. Surgically staged patients with poor prognosis stage III non-small-cell lung cancer were eligible for this study. Four-day continuous intravenous infusions of cisplatin 20 mg/m2/day, 5-fluorouracil 1,000 mg/m2/day, and etoposide 75 mg/m2/day were given concurrently with accelerated fractionation radiation therapy, 1.

Phase II trial of circadian infusion floxuridine (FUDR) in hormone refractory metastatic prostate cancer.

Circadian administration of chemotherapy has been reported to decrease toxicity and possibly enhance efficacy. Between March 1991 and December 1993, 18 evaluable patients with progressive, hormone-refractory metastatic prostate cancer were treated in this phase II trial of circadian infusion floxuridine (FUDR). The drug was delivered through a central venous catheter using a CADD-Plus computerized pump such that approximately 70% of the drug was administered between 3 and 9 p.

Approaches to managing carboplatin-induced thrombocytopenia: focus on the role of amifostine.

Thrombocytopenia is a significant problem for patients receiving prolonged or aggressive chemotherapy for malignancy. For carboplatin, it is the predominant dose-limiting toxicity and it is cumulative in nature. A number of agents have been evaluated for efficacy in reducing the problem of thrombocytopenia.

Signal transduction abnormalities in T lymphocytes from patients with advanced renal carcinoma: clinical relevance and effects of cytokine therapy.

Studies have demonstrated abnormalities of the CD3/T-cell antigen receptor (TCR) and pathways of signal transduction in T lymphocytes from animals and patients with advanced malignancy. Diminished expression of TCRzeta and p56(lck) that are associated with the TCR and reduced nuclear localization of RelA containing nuclear factor kappaB (NFkappaB) complexes have been noted. These defects have been described in T cells from patients with malignant melanoma, renal cell carcinoma (RCC), ovarian cancer, and colorectal cancer.

Intercomparison of radon and decay product measurements in an underground mine and EPA Radon Laboratory: a study organized by the IAEA International Radon Metrology Programme. International Atomic Energy Agency.

The International Atomic Energy Agency (IAEA) in Vienna and the European Union (EU) in Bruxelles formed the "International Radon Metrology Programme" (IRMP, scientific secretary: F. Steinhäusler, University of Salzburg, Austria). The IRMP is designed to assess and foster the improvement of radon and decay product measurements that are made around the world.

Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer.

Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor effects in preclinical systems, we performed a Phase I/II clinical trial of this combination in patients with advanced breast cancer. Patients with potentially hormone-responsive advanced breast cancer were enrolled. All received 20 mg of tamoxifen by mouth daily.

Multicenter randomized clinical trial of goserelin versus surgical ovariectomy in premenopausal patients with receptor-positive metastatic breast cancer: an intergroup study.

Purpose: To compare failure-free survival (FFS) and overall survival (OS) for patients with metastatic breast cancer treated with the gonadotropin-releasing hormone (GN-RH) agonist, goserelin versus surgical ovariectomy.

Patients And Methods: Between August 1, 1987 and July 15, 1995 138 (136 eligible) premenopausal patients with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive metastatic breast cancer were entered by the Southwest Oncology Group (SWOG), North Central Cancer Treatment Group (NCCTG), and Eastern Cooperative Oncology Group (ECOG). Prior chemotherapy or hormone therapy for metastatic disease was not allowed.

Randomized trial of carboplatin plus amifostine versus carboplatin alone in patients with advanced solid tumors.

Background: To test the hypothesis that the cytoprotectant amifostine attenuates the thrombocytopenia produced by carboplatin, the authors performed a randomized trial comparing treatment with carboplatin alone versus the combination of amifostine and carboplatin.

Methods: Patients with refractory or carboplatin-sensitive malignancies were randomized to receive either carboplatin, 500 mg/m2 alone or carboplatin, 500 mg/m2 in conjunction with 2 doses of amifostine of 910 mg/m2 each.

Results: Fifty-five patients with a variety of malignancies were entered on this study.

Phase II trial of interleukin-2 and interferon-alpha in patients with renal cell carcinoma: clinical results and immunologic correlates of response.

A phase II trial was conducted in patients with metastatic renal cell carcinoma, to assess the clinical efficacy and immunoregulatory effects of continuous-infusion recombinant interleukin-2 (rIL-2) (9.0 x 10(6) IU/m2/day on days 1-5, 8-12, 15-19, and 22-26) and subcutaneously administered recombinant human interferon-alpha 2b (rHuIFN alpha 2b) (10.0 x 10(6) U/m2/day TIW).

Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group phase III trial.

Purpose: A phase III randomized trial was performed to determine whether combination hormonal therapy with aminoglutethimide (AG) and hydrocortisone (HC) plus megestrol acetate (MA) improved response rates, response duration, or increased survival over the sequential use of each hormone in women with estrogen receptor-positive metastatic breast cancer (MBC) who had maintained stable disease for at least 6 months or responded to tamoxifen.

Patients And Methods: Two hundred eighty-eight postmenopausal women with progressive estrogen receptor-positive MBC were randomly selected to receive MA 40 mg four times daily (arm I), AG 250 mg four times daily with HC 40 mg daily in divided doses (arm II), versus the combination of MA plus AG given at the same dosages (arm III). Patients on arms I and II who progressed after an adequate trial were crossed over to the other treatment arm.

Pelvic computed tomography of breast carcinoma patients. Should it routinely be added to abdominal computed tomography?

Background: This study was conducted to determine if pelvic computed tomography (CT) should routinely be appended to abdominal CT in the workup of patients with breast carcinoma.

Methods: The abdominal-pelvic CTs of 139 breast carcinoma patients (195 exams) were reviewed. Scans were grouped by indication and whether pelvic pathology was known before CT.

Amifostine and chemotherapy-related thrombocytopenia.

Thrombocytopenia is a manifestation of hematopoietic toxicity that, at present, can be treated only with platelet transfusions. Thrombocytopenia is a dose-limiting toxicity for carboplatin, mitomycin-C, and other agents, and becomes dose limiting when granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor are used with some chemotherapeutic regimens; thus, strategies to reduce thrombocytopenia are needed. While clinical trials have begun using hematopoietic growth factors that have shown promising preclinical effects on thrombocytopenia, alternative approaches to modifying therapy-related thrombocytopenia are also being developed.

Ifosfamide in the treatment of soft tissue sarcomas.

Ifosfamide is one of the three most active agents in the treatment of soft tissue sarcomas. Ifosfamide-induced urothelial toxicity has been adequately controlled with the use of hydration and the uroprotective agent mesna. This is a review of pilot and phase I and II studies of ifosfamide as a single agent and randomized trials of combination chemotherapy regimens incorporating ifosfamide in the treatment of soft tissue sarcomas.

Phase II trial of subcutaneously administered granulocyte-macrophage colony-stimulating factor in patients with metastatic renal cell carcinoma.

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is involved in the differentiation and proliferation of various hematopoietic precursors. It also has been reported to enhance the antitumor activity of various mature effector cells. Previous reports have noted preclinical antitumor activity in a murine model utilizing genetically engineered tumor cells and instances of tumor regression in patients with solid tumors receiving GM-CSF.

Phase I trial of subcutaneous interleukin 3 in patients with refractory malignancy: hematological, immunological, and pharmacodynamic findings.

We conducted a Phase I trial of s.c. recombinant human interleukin 3 (rhIL-3) to evaluate the toxicity, maximal tolerated dose, pharmacokinetics, and in vivo biological effects of this cytokine.

Clinical effects of amifostine (Ethyol) in patients treated with carboplatin.

Amifostine is a compound that has been developed as a radio- and chemoprotectant. It is a prodrug, giving rise to the active thiol, WR-1065. Amifostine has been demonstrated to reduce the toxicity of ionising radiation, alkylating agents and platinum compounds.

Immunomodulatory effects of interleukin-2 and interleukin-4 in patients with malignancy.

A phase I trial of simultaneously administered recombinant interleukin-2 (rIL-2) and recombinant human IL-4 (rHuIL-4) was conducted to evaluate the toxicity and the clinical and immunologic effects of this cytokine combination. Thirty-nine eligible patients with refractory malignancy were treated at eight different dose levels (1A to 3B): 1-3 of rIL-2 [3.0, 12.

Accelerated induction therapy and resection for poor prognosis stage III non-small cell lung cancer.

Background: Induction therapy and resection may improve the survival of patients with poor prognosis stage III non-small cell lung cancer, at the cost of significant treatment prolongation. The purpose of this study was to assess toxicity, response, and survival of an accelerated induction regimen and resection in poor prognosis stage III non-small cell lung cancer.

Methods: Forty-two surgically staged patients with poor prognosis stage III non-small cell lung cancer received 11 days of induction treatment consisting of 96 hours of continuous chemotherapy infusions of cisplatin (20 mg.

Effects of thermal, personal and behavioural factors on the physiological strain, thermal comfort and productivity of Australian shearers in hot weather.

Multiple-regression analyses were used to evaluate the separate and combined effects of factors that are commonly expected to influence strain and productivity in a hot workplace. Forty-three men were studied throughout 54 man-days of shearing sheep and pressing wool bales, in air temperatures 19-41 degrees C and Wet-bulb Globe Temperature index (WBGT) 16-29 degrees C; 43% of the observations of WBGT exceeded 26.7 degrees C, the Threshold Limit Value (TLV) for the subjects' work rate of 400 W.

Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study.

Purpose: To compare 1 year of therapy with continuous cyclophosphamide, methotrexate, fluorouracil (5-FU), vincristine, and prednisone (CMFVP) with a short course of treatment with a doxorubicin-based regimen in the postsurgical adjuvant treatment of patients with hormone receptor-negative, node-positive breast cancer.

Patients And Methods: Five-hundred thirty-one eligible women with hormone receptor-negative, node-positive breast cancer were randomized to receive either 1 year of therapy with CMFVP or 20 weeks of therapy with four 5-week courses of treatment with 5-FU, doxorubicin, cyclophosphamide, and methotrexate (FAC-M).

Results: At a median follow-up time of 4.