PubMed Health⌕ Search

Biomedical subjects

J Gutheil

Publications and source records attributed to J Gutheil.

9 recordsLinked to original sources
PubMed2001

Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.

PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.

Adult↗
PubMed2000

A pilot study of the anti-CD20 monoclonal antibody rituximab in patients with refractory immune thrombocytopenia.

We conducted a prospective pilot phase I/II clinical trial to evaluate the toxicity and response rate of the chimeric anti-CD20 monoclonal antibody, rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceutical Corporation, San Diego, CA), in the treatment of patients with immune thrombocytopenic purpura. Patients with a clinical diagnosis of idiopathic thrombocytopenic purpura who had failed corticosteroid therapy and whose platelet count was less than 75,000/microL were eligible for the study. Rituximab was administered in a dose-escalation fashion using doses ranging from 50 to 375 mg/m2 weekly for 4 weeks. Thirteen patients have been enrolled on the trial to date and 12 have completed the full course of treatment. No unusual toxicity was noted in this patient population. None of the three patients at the lowest dose level achieved a clinical response. Three of nine patients (30%) who have received rituximab at doses close or equal to the full dose have shown an objective clinical response (two complete responses, one partial response). The study is currently ongoing, and conclusions regarding the overall response rate, clinical parameters that influence response, surrogate markers of response, and the underlying mechanism of response remain to be addressed. The current study should provide answers to a number of important questions regarding the role of rituximab in the treatment of this and other autoimmune disorders.

Adult↗
PubMed1999

Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma.

PURPOSE: Yttrium-90 ibritumomab tiuxetan (IDEC-Y2B8) is a murine immunoglobulin G1 kappa monoclonal antibody that covalently binds MX-DTPA (tiuxetan), which chelates the radioisotope yttrium-90. The antibody targets CD20, a B-lymphocyte antigen. A multicenter phase I/II trial was conducted to compare two doses of unlabeled rituximab given before radiolabeled antibody, to determine the maximum-tolerated single dose of IDEC-Y2B8 that could be administered without stem-cell support, and to evaluate safety and efficacy. PATIENTS AND METHODS: Eligible patients had relapsed or refractory (two prior regimens or anthracycline if low-grade disease) CD20(+) B-cell low-grade, intermediate-grade, or mantle-cell non-Hodgkin's lymphoma (NHL). There was no limit on bulky disease, and 59% had at least one mass > or = 5 cm. RESULTS: The maximum-tolerated dose was 0.4 mCi/kg IDEC-Y2B8 (0.3 mCi/kg for patients with baseline platelet counts 100 to 149,000/microL). The overall response rate for the intent-to-treat population (n = 51) was 67% (26% complete response [CR]; 41% partial response [PR]); for low-grade disease (n = 34), 82% (26% CR; 56% PR); for intermediate-grade disease (n = 14), 43%; and for mantle-cell disease (n = 3), 0%. Responses occurred in patients with bulky disease (> or = 7 cm; 41%) and splenomegaly (50%). Kaplan-Meier estimate of time to disease progression in responders and duration of response is 12.9+ months and 11.7+ months, respectively. Adverse events were primarily hematologic and correlated with baseline extent of marrow involvement with NHL and baseline platelet count. One patient (2%) developed an anti-antibody response (human antichimeric antibody/human antimouse antibody). CONCLUSION: These phase I/II data demonstrate that IDEC-Y2B8 radioimmunotherapy is a safe and effective alternative for outpatient therapy of patients with relapsed or refractory NHL. A phase III study is ongoing.

Adolescent↗
PubMed1999

Radioimmunotherapy of relapsed non-Hodgkin's lymphoma with zevalin, a 90Y-labeled anti-CD20 monoclonal antibody.

Approximately 55,400 new cases of non-Hodgkin's lymphoma (NHL) are diagnosed each year, with the overall prevalence of the disease now estimated to be 243,000. Until recently, treatment alternatives for advanced disease included chemotherapy with or without external beam radiation. Based on the results of several clinical trials, the chimeric monoclonal antibody Rituximab has now been approved by the United States Food and Drug Administration as a treatment for patients with relapsed or refractory, low-grade or follicular, B-cell NHL. Several other monoclonal antibodies in conjugated and unconjugated forms have been evaluated in the treatment of NHL. Ibritumomab, the murine counterpart to Rituximab, radiolabeled with 90Y (Zevalin), is presently being evaluated in clinical trials. The success of radioimmunotherapy is dependent upon the appropriate choice of antibody, isotope, and chelator-linker. The Ibritumomab antibody targets the CD20 antigen. The antibody is covalently bound to the chelator-linker tiuxetan (MX-DTPA), which tightly chelates the isotope 90Y. To date, two Phase I/II Zevalin clinical trials have been completed in patients with low-grade, intermediate-grade, and mantle cell NHL. The overall response rate was 64% in the first trial and 67% in the later trial. Phase II and III trials are ongoing.

Antibodies, Monoclonal↗
PubMed1992

Potential applications of high-dose megestrol acetate in breast cancer.

Empiric clinical trials have revealed new mechanisms by which hormonal therapies may exert their antitumor effects. Initial studies using escalated doses of agents like toremifene and megestrol acetate have yielded interesting results, showing responses in hormone-receptor-negative patients and in patients progressing after standard doses, respectively. A trial by Cancer and Leukemia Group B randomizing patients with advanced breast cancer to standard-dose (160 mg) megestrol acetate or to 5 or 10 times the standard dose (800 and 1,600 mg) has completed accrual. It is hoped that these results will provide a definitive answer to the dose-response issue for breast cancer. However, regardless of this trial's ultimate outcome, higher doses of megestrol acetate have demonstrated important new effects on appetite stimulation and weight gain; ongoing laboratory research promises potential roles for megestrol acetate in the reversal of chemotherapeutic drug-induced tumor resistance.

Adult↗
PubMed1979

Antineoplastic activity of poly(L-lysine) with some ascites tumor cells.

We have found that poly(L-lysine) can be a very effective agent in preventing the growth of Ehrlich ascites tumors in mice. When given optimal doses of poly(L-lysine) (Mr 60 x 10(3)) intraperitoneally for 5 consecutive days, beginning on day 1 after inoculation with Ehrlich ascites cells. White Swiss mice show nearly a 100% remission from subsequent tumor growth. Rechallenge of "cured" animals with tumor cells, however shows no long-term immunological protection. In tissue culture, poly(L-lysine) shows a related potent cytotoxicity with HeLa cells; interestingly, the D isomer. In addition, there is a strong molecular weight dependence in that the small polylysine (Mr 3 x 10(3)) possesses less than 1/20th the cytotoxicity of large polymers (Mr 70 x 10(3)) on a weight basis in both cell culture and animal studies. At the same time, none of these lysine polymers gives any significant increase in life span to BDF1 mice infected with L1210 murine leukemia cells. We have also further explored the mechanism by which the polylysines express their cytotoxicity. These data indicate that lysine polymers show cell specificity in their action and in some cases they may be beneficial as potent antineoplastic agents, particularly when molecular weight is taken into consideration.

Animals↗