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Biomedical subjects

J Neidhart

Publications and source records attributed to J Neidhart.

At least 19 recordsLinked to original sources
PubMed1997

Phase 1 trial of recombinant human interleukin-1 beta (rhIL-1 beta), carboplatin, and etoposide in patients with solid cancers: Southwest Oncology, Group Study 8940.

Recombinant human interleukin-1 beta (rhIL-1 beta) was evaluated in a phase 1 clinical trial in which patients with metastatic or unresectable solid tumors received carboplatin and etoposide in cycle 1 and carboplatin, etoposide, and rhIL-1 beta in cycle 2. Recombinant hIL-1 beta was given intravenously for 5 days in one of three schedules: (1) immediately postchemotherapy, (2) delayed for 5 days after chemotherapy, or (3) concurrently with chemotherapy. Four dose levels of rhIL-1 beta were evaluated: 20, 50, 100, and 200 ng/kg. The doses of carboplatin and etoposide were not changed between cycle 1 and cycle 2 so that the effect of rhIL-1 beta on chemotherapy-induced hemato-toxicity was evaluated; 54 patients were entered on study and 42 patients received at least two cycles of therapy and were thus evaluable for rhIL-1 beta toxicity and for the effect of rhIL-1 beta on hematotoxicity of carboplatin and etoposide. The major toxicities of rhIL-1 beta were chills, rigors, headache, fatigue, and hypotension. The maximum tolerated dose of rhIL-1 beta was not determined since the toxicities at all dose levels were similar. However, only 3/8 patients at the 200 ng/kg level received all 5 IL-1 beta infusions. We compared the effect of rhIL-1 beta on hematotoxicity of carboplatin/etoposide by comparing peripheral blood count parameters between cycles 1 and 2: rhIL-1 beta given postchemotherapy significantly increased absolute neutrophil count (AND) nadirs and improved neutrophil recovery times regardless of rhIL-1 beta dose level. Platelet count parameters were also improved when rhIL-1 beta was given postchemotherapy although these changes did not reach statistical significance. Thus, IL-1 beta exhibited extensive hematological effects but the usefulness of this agent in clinical practice will be limited by extensive toxicity at all tested dose levels.

Adult↗
PubMed1993

Multicenter phase II study of brequinar sodium in patients with advanced gastrointestinal cancer.

Eighty-six patients with advanced colorectal, gastric or pancreatic carcinoma and no prior exposure to chemotherapy were treated with brequinar sodium. Brequinar was administered at a median weekly dose of 1200 mg/m2 intravenously. The toxicity was moderate, with thirty patients (35%) experiencing grade 3 or 4 toxicity. Objective responses were observed in 1/32 evaluable colorectal and 2/29 evaluable gastric carcinoma patients. There were no objective responses in 17 evaluable pancreatic cancer patients. We conclude that, at this dose and schedule, brequinar does not have sufficient activity in these gastrointestinal malignancies to warrant further evaluation.

Adult↗
PubMed1992

SWOG 8825: melphalan GM-CSF: a phase I study.

The use of intravenous melphalan at higher doses is limited by severe myelosuppression. It was postulated that GM-CSF would permit the use of higher dose melphalan with only moderate myelosuppression easily manageable in an outpatient setting. Therefore, a phase I study of intravenous melphalan utilizing GM-CSF (recombinant granulocyte-macrophage colony-stimulating factor) support was initiated. Intravenous melphalan at doses of 15-45 mg/m2 was administered every 28 days. GM-CSF was utilized at doses of 10-20 micrograms/kg/day subcutaneously Days 2-21 on a 28-day cycle. Twenty-five patients received 53 courses of therapy. The dose-limiting toxicities were severe or life-threatening granulocytopenia and thrombocytopenia. Utilizing 20 micrograms/kg/day GM-CSF, the maximum tolerated dose (MTD) of melphalan is 30 mg/m2 and, with 10 mg/kg/day GM-CSF, the maximum tolerated melphalan dose is only 20 mg/m2. One patient with ovarian cancer achieved a partial response. Because the reported MTD of intravenous melphalan without GM-CSF is 30 mg/m2, GM-CSF has not allowed sufficient escalation of the intravenous melphalan dose for routine outpatient use.

Adenocarcinoma↗
PubMed1992

Comparative study of pamidronate disodium and etidronate disodium in the treatment of cancer-related hypercalcemia.

PURPOSE: This multicenter, double-blind, randomized trial was performed to determine the efficacy and safety of pamidronate disodium (APD) in comparison to etidronate disodium (EHDP) in the treatment of cancer-related hypercalcemia. PATIENTS AND METHODS: Sixty-five male and female adult patients with cancer and corrected calcium levels of greater than or equal to 12.0 mg/dL after 24 hours of hydration were randomized to receive either 60 mg APD given as a single 24-hour infusion or 7.5 mg/kg EHDP given as a 2-hour infusion daily for 3 days. RESULTS: APD normalized corrected calcium levels in 70% (21 of 30) of patients, whereas EHDP did so in 41% (14 of 34) of patients (P = .026). The mean corrected serum calcium level decreased from 14.6 to 10.5 mg/dL in the APD-treated group and from 13.8 to 11.6 mg/dL in the EHDP-treated group within the first week of treatment. There was no difference in response to APD in patients without versus those with bone metastases (78% v 67%). Both drugs were well tolerated. CONCLUSION: This study demonstrated that a single 60-mg infusion of APD is safe and more effective than EHDP given at the dose of 7.5 mg/kg for 3 days in the treatment of cancer-related hypercalcemia.

Adult↗
PubMed1991

Randomized trial of doxorubicin, bisantrene, and mitoxantrone in advanced breast cancer: a Southwest Oncology Group study.

Four hundred eleven women with metastatic breast cancer were randomly assigned to receive either 60 mg/m2 doxorubicin (130 patients), 320 mg/m2 bisantrene (146 patients), or 14 mg/m2 mitoxantrone (135 patients). The doses were given intravenously every 3 weeks with a cross-over design to determine their relative efficacy and toxicity. To be eligible, patients must have had one previous chemotherapy regimen, and patients who were estrogen receptor positive must have failed endocrine therapy. There were 365 patients assessable for response and 399 assessable for toxic effects. The median age was 57 years; 18% were premenopausal or perimenopausal. Visceral dominant disease was present in 66% of the patients. Ninety-seven percent of the patients had a disease-free interval from diagnosis to first recurrence of less than 1 year. The response rate was 28% with doxorubicin, 13% with bisantrene, and 14% with mitoxantrone (P = .004). Median time to treatment failure was 133 days with doxorubicin, 66 days with bisantrene, and 68 days with mitoxantrone (logrank P = .06). The median survival was 315 days for doxorubicin, 290 days for bisantrene, and 177 days for mitoxantrone (logrank P = .04), although survival at 2 years was similar for all three agents. There were five responses in the 66 patients crossed over to doxorubicin and one response each for patients crossed over to bisantrene (39 patients) or mitoxantrone (63 patients). Toxicity leading to discontinuance of therapy was more common with doxorubicin, and discontinuance of therapy was due primarily to patient's request or cardiotoxicity. The major dose-limiting toxic effect for all three agents was leukopenia. Nausea and vomiting, mucositis, and alopecia were more severe with doxorubicin. Congestive heart failure developed in nine patients treated with doxorubicin, zero patients treated with bisantrene, and two patients treated with mitoxantrone. A decrease in the left ventricular ejection fraction, as defined by moderate to severe Alexander grade changes, was more common in patients treated with doxorubicin (doxorubicin-treated patients = 20%, bisantrene-treated patients = 5%, and mitoxantrone-treated patients = 10%). This study demonstrates that bisantrene and mitoxantrone have only modest activity in metastatic breast carcinoma. The activity of doxorubicin is greater than that of the other two agents, but at a cost of increased toxicity.

Adenocarcinoma↗
PubMed1991

Amikacin pharmacokinetics in patients receiving high-dose cancer chemotherapy.

We retrospectively analyzed amikacin pharmacokinetics in 28 patients (mean age, 47.4 +/- 13.6 years) who received high-dose chemotherapy during a neutropenic febrile episode. Patients received an experimental protocol of high-dose anticancer chemotherapy. Amikacin pharmacokinetic parameters were calculated from two or more concentrations in serum around a single dose by the method of Sawchuck and Zaske (J. Pharmacokinet. Biopharm. 4:183-195, 1976). Predicted parameters were calculated by using standard methods. The observed amikacin volume of distribution and clearance were significantly greater and the elimination half-life was longer than predicted (0.38 +/- 0.13 versus 0.25 liter/kg [P = 0.0001], 1.51 +/- 0.92 versus 1.17 +/- 0.38 liters/h/kg [P = 0.012], and 3.8 +/- 2.4 versus 2.9 +/- 1.1 h [P = 0.011], respectively). Multivariate analysis revealed that albumin correlated negatively and creatinine correlated positively with the volume of distribution and the elimination half-life. Creatinine and the percentage below the ideal body weight correlated negatively and hematocrit correlated positively with clearance. Administration of dosage regimens based on predicted pharmacokinetic parameters yielded subtherapeutic amikacin concentrations in serum in our patients. Because of the increased dosage requirements and the need for adequate antibiotic treatment in this population, we suggest guidelines for empiric dosing for patients with advanced cancer receiving intensive chemotherapy.

Adolescent↗
PubMed1990

A comprehensive phase I and II clinical investigation of fludarabine phosphate.

This article presents data from the phase I and II clinical investigations of Fludara I.V. (fludarabine phosphate) (NSC 312887), which is the 5'-phosphorylated derivative of the novel antimetabolite, 9-beta-D-arabinofuranosyl-2-fluoroadenine. The comprehensive phase I evaluation of this new antitumor agent was conducted in 51 patients with advanced malignancy and 15 additional patients with aggressive forms of leukemia. Three separate phase I schedules of drug administration were examined. Myelosuppression was the dose-limiting toxicity on each schedule administered to patients with solid tumors. The drug was also examined at higher doses in patients with leukemia, and the dose-limiting toxicity on the high-dose protocol was unacceptable: serious neurologic toxicity. The observation of antitumor responses in patients with advanced non-Hodgkin's lymphoma prompted additional phase II investigation in patients with lymphoproliferative malignancy. The encouraging phase II data demonstrate that Fludara I.V. has promise for patients with low-grade histologic subtypes of non-Hodgkin's lymphoma and chronic lymphocytic leukemia. While interesting additional basic and clinical research projects regarding Fludara I.V. remain, it is important to expeditiously pursue approval for this drug. Adequate data exists to demonstrate that the low-dose administration of Fludara I.V. is both safe and effective. While the development of this drug has stimulated renewed interest in the clinical investigation of the chronic lymphoproliferative malignancies, the time for making it readily available to these patients has arrived.

Adult↗
PubMed1989

Peripheral blood morphologic changes after high-dose antineoplastic chemotherapy and recombinant human granulocyte colony-stimulating factor administration.

The peripheral blood morphologic findings in 17 patients with cancer who had received high-dose cytotoxic chemotherapy followed by recombinant human-granulocyte colony-stimulating factor (rh-GCSF) were reviewed and compared with a control group of patients who received only high-dose chemotherapy. Both groups showed dysmyelopoiesis (abnormal granulation and nuclear lobulation) in the granulocytic series during the period of bone marrow recovery that followed the cytotoxic chemotherapy. Most of these morphologic abnormalities were more prominent in the rh-GCSF-treated group. Monocytic cells in both groups showed prominent vacuolation and immature nuclei. The percentages and absolute numbers of large granular lymphocytes were increased in the rh-GCSF group compared with the control group. No quantitative or qualitative abnormalities of eosinophilic or basophilic granulocytes were detected in either group. Both groups showed nonspecific red blood cell abnormalities, and large platelets were present in half of the control group smears. This report provides the first detailed peripheral blood morphologic description in patients treated with rh-GCSF and high-dose chemotherapy.

Adult↗
PubMed1989

Granulocyte colony-stimulating factor stimulates recovery of granulocytes in patients receiving dose-intensive chemotherapy without bone marrow transplantation.

Bone marrow colony-stimulating factors (CSF) ameliorate hematologic toxicity of standard chemotherapy regimens and may allow relatively safe use of intensive and more efficacious doses of anticancer drugs. Twenty-four patients with cancers for which no standard regimens were likely to be effective received repeated courses of a combination of cisplatin (150 mg/m2), etoposide (1,500 mg/m2), and cyclophosphamide (5,000 mg/m2) at doses for which bone marrow transplantation is usually used. A total of 10 patients received escalating doses of recombinant human granulocyte CSF (rhG-CSF); 11 patients receiving identical chemotherapy and supportive therapy without rhG-CSF served as controls for the first cycle of therapy. Five of these patients and 3 additional patients also served as their own controls, receiving rhG-CSF for all cycles after the first. No patient received bone marrow transplantation. rhG-CSF shortened the median duration of severe granulocytopenia (less than or equal to 100/mm3) in a dose-related fashion (P less than .03; Kruskal-Wallis test). Patients not receiving rhG-CSF had a median of 8.5 days of granulocytopenia. Those receiving 40 micrograms/kg of rhG-CSF for approximately 20 days from the third day after chemotherapy had a median of 7.0 days (P less than .23) and those receiving 60 micrograms/kg had a median of 5.5 days (P less than .007) of granulocytopenia. An rhG-CSF dose of 20 micrograms/kg had no effect. Recovery to a granulocyte count of at least 500/mm3 took a median of 12 days in the control group and 8 days (P less than .03) in patients receiving rhG-CSF at a dose of 60 mg/kg. The duration of antibiotic therapy (a median, 9.0 days v 5.0 days) was shortened with the two higher and effective doses of rhG-CSF compared with control patients. The duration of hospitalization (median of 20 days v 19 days) was not shortened. These findings that rhG-CSF decreases the risk of granulocytopenia associated with this particular dose-intensive chemotherapy regimen therapy administered without bone marrow transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Phase I study of recombinant gamma-interferon (rIFN-gamma).

A Phase I study of recombinant gamma-interferon was conducted in 35 patients with advanced malignancy. The schedule was twice weekly administered intravenously. Patients were assigned to six dose levels. The major toxicities were flu-like symptoms and were unrelated to dose. Other adverse reactions, such as myelosuppression, were dose dependent. The addition of a nonsteroidal anti-inflammatory agent did not ameliorate the symptoms at the highest dose level. Antitumor effects occurred in patients with gastric, duodenal, and breast carcinoma.

Drug Evaluation↗
PubMed1987

Phase II trial of MVE-II in metastatic malignant melanoma.

MVE-II, a low molecular weight fraction of pyran copolymer was utilized in a Phase II trial in patients with metastatic malignant melanoma. A total of 15 patients were investigated and no clinical responses or immunologic responses were observed. We concluded that MVE-II is not an active agent in malignant melanoma.

Adult↗
PubMed1987

Phase I/II trial of recombinant gamma-interferon in patients with renal cell carcinoma: immunologic and biologic effects.

Thirteen patients with metastatic renal cell carcinoma were entered on a Phase I/II trial of recombinant gamma-interferon (gamma-IFN). Patients (3) were entered on escalating dose levels, and each patient was escalated to the next dose until an individual maximum tolerated treatment dose (MTD) was established. Multiple parameters of biologic response were measured. Patients were studied twice baseline and at frequent intervals after the initial treatment and every treatment until the patient's individual MTD was reached. The MTD for most patients was less than 75 X 10(6) U/m2. Small, but statistically significant, enhancement of monocyte antibody-dependent cellular cytotoxicity and mononuclear cell inhibition of MBL-2 growth were noted in vitro at gamma-IFN concentrations greater than 250 U/ml. Clinically obvious biologic effects were observed: fever, chills, hypotension, and malaise. However, laboratory assays of peripheral blood mononuclear cell natural killer cell activity, tumor (MBL-2) growth inhibition, antibody-dependent cellular cytotoxicity, lymphoblastic T-cell subsets, and 2'5'-oligonucleotide synthetase were not altered in vivo.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

Lack of benefit of adjunctive chemotherapy in stage I malignant melanoma: a Southwest Oncology Group Study.

In 1975, the Southwest Oncology Group initiated an adjuvant study in localized malignant melanoma testing the value of aggressive chemotherapy using carmustine, hydroxyurea, and dacarbazine versus a control arm. Median disease-free survival was 7.1 years for the control arm and 6 years for the treatment arm. Survival was identical for both arms with 65% of the patients alive at 6 years. We conclude that carmustine, hydroxyurea, and dacarbazine chemotherapy is of no value as adjuvant treatment for localized melanoma.

Adult↗
PubMed1986

Phase I/II trial of human recombinant beta-interferon serine in patients with renal cell carcinoma.

Beta-interferon serine (IFN-beta ser) is a genetically altered recombinant IFN with a specific activity of 2 X 10(8) IU/mg protein. We undertook a Phase I trial of this agent in 18 patients with metastatic renal cell carcinoma. IFN-beta ser was given by a 4-h intravenous infusion twice weekly (Monday and Thursday). Three patients were placed on escalating dose levels. Doses were also escalated in each patient if no unacceptable toxicity was detected on the previous treatment. The maximum initial tolerated dose was less than or equal to 150 million units/m2. However, development of patient tolerance allowed escalation beyond this dose and chronic therapy at this or higher doses in most patients. Toxicity was largely limited to the symptom complex of fever, malaise, mild hypotension, and anorexia. One patient developed reversible proteinuria (10 g/24 h) with no change in serum creatinine. Limited or no renal, hepatic, or hematological toxicity was observed. Six of 16 patients developed anti-IFN antibody levels. Fifteen patients received twice weekly treatments at near their maximum tolerated dose for greater than or equal to 4 weeks and were evaluable for response. Two patients developed a partial and one patient a minor response. We conclude that IFN-beta ser is a well tolerated IFN with minimal renal, hepatic, and bone marrow toxicity. It has apparent activity in metastatic renal cell carcinoma.

Aged↗
PubMed1984

A randomized trial of metoclopramide and a combination of dexamethasone and lorazepam for prevention of chemotherapy-induced vomiting.

In a randomized, crossover design the antiemetic activity of one of the most active single agents, metoclopramide was compared with a combination of dexamethasone and lorazepam. Both regimens were effective, but dexamethasone-lorazepam was significantly better than metoclopramide in preventing (26% versus 13%) or limiting (44% versus 23%) vomiting. Although side effects were more frequent with lorazepam-dexamethasone, the patients generally judged them desirable and overall patient preference was strong (70% versus 12%) for the lorazepam-dexamethasone combination. Patients required supervision and assistance due to lorazepam-induced drowsiness.

Adolescent↗
PubMed1983

The Southwest Oncology Group experience: adjuvant therapy for stage IB and II non-seminomatous testicular cancer.

During a two year period, 65 patients with Stage II non-seminomatous testis cancer were randomized to receive adjuvant chemotherapy and radiation. Of the 52 evaluable patients, 23 received radiation followed by chemotherapy (sequential), and 29 received the same chemotherapy as initial treatment, but had drug treatment temporarily interrupted for radiation (sandwich). The combined treatment was well tolerated, but did not eliminate recurrence. With regard to duration of survival and disease-free survival, no statistically significant difference could be found between the sequential and sandwich approaches.

Adult↗