scholarly journals In vitro testing of calcium channel blockers and cytotoxic chemotherapy in B-cell low-grade non-Hodgkin's lymphoma

1998 ◽  
Vol 77 (10) ◽  
pp. 1598-1603 ◽  
Author(s):  
J Shamash ◽  
AH Salam ◽  
DC Davies ◽  
A Williams ◽  
S Joel ◽  
...  
Keyword(s):  
Calcium Channel ◽  
B Cell ◽  
Calcium Channel Blockers ◽  
Cytotoxic Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
In Vitro Testing ◽  
Channel Blockers ◽  
Non Hodgkin's Lymphoma

Pharmacokinetic Study of Single Doses of Oral Fludarabine Phosphate in Patients With “Low-Grade” Non-Hodgkin's Lymphoma and B-Cell Chronic Lymphocytic Leukemia

1999 ◽  
Vol 17 (5) ◽  
pp. 1574-1574 ◽  
Author(s):  
James M. Foran ◽  
David Oscier ◽  
Jennifer Orchard ◽  
Stephen A. Johnson ◽  
Mary Tighe ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Intravenous Administration ◽  
Pharmacokinetic Study ◽  
Lymphocytic Leukemia ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Fludarabine Phosphate ◽  
Non Hodgkin's Lymphoma ◽  
Cell Chronic Lymphocytic Leukemia

PURPOSE: Fludarabine phosphate (F-AMP), a purine analog, requires daily intravenous administration. A pharmacokinetic study of an oral formulation (10 mg immediate-release tablet) was undertaken in patients with “low-grade” non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia. PATIENTS AND METHODS: Oral F-AMP was incorporated into the “conventional” treatment schedule. Single oral trial doses of 50, 70, and 90 mg of F-AMP were given on the first day of three cycles of treatment; a comparative 50-mg intravenous trial dose was given on the first day of the fourth cycle. Intravenous F-AMP (25 mg/m2) was given on days 2 to 5 at 4-week intervals. Pharmacokinetic samples taken after each trial dose were analyzed for plasma 2-fluoro-arabinofuranosyl-adenine (2F-ara-A) concentration (its main metabolite); area under the curve 0 to 24 hours (AUC(0-24h)) and maximum concentration (Cmax) were calculated. Eighteen patients received all three oral trial doses, and bioavailability was determined in 15 patients who completed four courses of therapy. RESULTS: Oral administration of F-AMP resulted in a dose-dependent increase in Cmax and AUC(0-24h) of 2F-ara-A and achieved an AUC(0-24h) similar to intravenous administration, although at a lower Cmax. The linear increase in mean AUC(0-24h) by factors of 1.36 ± 0.22 (mean ± SD) and 1.72 ± 0.31 corresponded well with the increase in oral dose from 50 to 70 mg (factor of 1.4) and 90 mg (factor of 1.8), respectively. Bioavailability (approximately 55%, with low intraindividual variation) and time to Cmax were dose independent. CONCLUSION: Oral doses of F-AMP can achieve an AUC(0-24h) of 2F-ara-A similar to intravenous administration, with dose-independent bioavailability. The tablet will greatly enhance the use of F-AMP in a palliative setting.

Prolonged Clinical and Molecular Remission in Patients With Low-Grade or Follicular Non-Hodgkin's Lymphoma Treated With Rituximab Plus CHOP Chemotherapy: 9-Year Follow-Up

2004 ◽  
Vol 22 (23) ◽  
pp. 4711-4716 ◽  
Author(s):  
Myron S. Czuczman ◽  
Robin Weaver ◽  
Baha Alkuzweny ◽  
Judy Berlfein ◽  
Antonio J. Grillo-López
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Molecular Remission ◽  
Prior Chemotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose Long-term follow-up with updated time to disease progression (TTP) and duration of response (DR) data are presented from a multicenter, phase II trial of rituximab/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination therapy in 40 patients with CD20+, B-cell, non-Hodgkin's lymphoma (NHL). Revised response rates based on International Workshop Response Criteria are also provided. Patients and Methods Enrollment began in April 1994 and consisted of patients with histologically confirmed, low-grade, B-cell lymphoma who had received no prior chemotherapy or who had no more than four prior standard therapies. Patients received six cycles of CHOP and six infusions of rituximab. Results Eight (21%) of the 38 treated patients were classified as International Working Formulation (IWF) A, 16 (42%) were IWF B, 13 (34%) were IWF C, and one (3%) was IWF D. Nine (24%) of 38 patients had received prior chemotherapy. Nine (24%) of 38 were considered poor risk according to the Follicular Lymphoma International Prognostic Index. Overall response rate was 100%; 87% of patients achieved a complete response or unconfirmed complete response. The median TTP and DR were 82.3 months and 83.5 months, respectively. Seven of eight patients who were bcl-2 positive at baseline converted to negative, and three of the seven patients have sustained the molecular remission. Conclusion Although a cure has not been found yet for follicular NHL, the R-CHOP combination provides a lengthy response duration in patients with relapsed or newly diagnosed indolent NHL.

Growth inhibition of human cancer cells in vitro by T-type calcium channel blockers

2006 ◽  
Vol 16 (19) ◽  
pp. 5014-5017 ◽  
Author(s):  
Jae Yeol Lee ◽  
Seong Jun Park ◽  
Sung Jun Park ◽  
Min Joo Lee ◽  
Hyewhon Rhim ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Calcium Channel ◽  
Cancer Cells ◽  
Calcium Channel Blockers ◽  
Human Cancer ◽  
Channel Blockers ◽  
Human Cancer Cells

scholarly journals Investigation of Calcium Channel Blockers as Antiprotozoal Agents and Their Interference in the Metabolism ofLeishmania (L.) infantum

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Juliana Quero Reimão ◽  
Juliana Tonini Mesquita ◽  
Daiane Dias Ferreira ◽  
Andre Gustavo Tempone
Keyword(s):  
Calcium Channel ◽  
Chagas Disease ◽  
Calcium Channel Blockers ◽  
Channel Blockers ◽  
Antiprotozoal Activity ◽  
Additive Interaction ◽  
Therapeutic Class ◽  
Species Production

Leishmaniasis and Chagas disease are neglected parasitic diseases endemic in developing countries; efforts to find new therapies remain a priority. Calcium channel blockers (CCBs) are drugs in clinical use for hypertension and other heart pathologies. Based on previous reports about the antileishmanial activity of dihydropyridine-CCBs, this work aimed to investigate whether thein vitroanti-Leishmania infantumand anti-Trypanosoma cruziactivities of this therapeutic class would be shared by other non-dihydropyridine-CCBs. Except for amrinone, our results demonstrated antiprotozoal activity for fendiline, mibefradil, and lidoflazine, with IC50values in a range between 2 and 16 μM and Selectivity Index between 4 and 10. Fendiline demonstrated depolarization of mitochondrial membrane potential, with increased reactive oxygen species production in amlodipine and fendiline treatedLeishmania, but without plasma membrane disruption. Finally,in vitrocombinations of amphotericin B, miltefosine, and pentamidine againstL. infantumshowed in isobolograms an additive interaction when these drugs were combined with fendiline, resulting in overall mean sum of fractional inhibitory concentrations between 0.99 and 1.10. These data demonstrated that non-dihydropyridine-CCBs present antiprotozoal activity and could be useful candidates for futurein vivoefficacy studies against Leishmaniasis and Chagas’ disease.

Phase I/II Trial of IDEC-Y2B8 Radioimmunotherapy for Treatment of Relapsed or Refractory CD20+ B-Cell Non-Hodgkin's Lymphoma

1999 ◽  
Vol 17 (12) ◽  
pp. 3793-3803 ◽  
Author(s):  
Thomas E. Witzig ◽  
Christine A. White ◽  
Gregory A. Wiseman ◽  
Leo I. Gordon ◽  
Christos Emmanouilides ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Intermediate Grade ◽  
Bulky Disease ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Yttrium 90

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 ≥ 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/μL). 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 (≥ 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.

Effect of aminophylline-Ca2+ blocker interaction on membrane potential of rat diaphragm fibers

1993 ◽  
Vol 74 (6) ◽  
pp. 2745-2749 ◽  
Author(s):  
O. Delbono ◽  
B. A. Kotsias
Keyword(s):  
Membrane Potential ◽  
Calcium Channel ◽  
Calcium Channel Blockers ◽  
Intrinsic Activity ◽  
Resting Membrane Potential ◽  
Maximum Effect ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Rat Diaphragm

We studied the antagonism between aminophylline and two calcium channel blockers, nifedipine and verapamil, and its effect on the resting membrane potential of rat diaphragm fibers in vitro at 25 degrees C. Aminophylline hyperpolarizes the fibers in a dose-dependent manner, and the maximum effect is reached with 1 mM of the drug, approximately 9 mV compared with normal values. Both nifedipine and verapamil (1–5 microM) decreased the amount of hyperpolarization induced by aminophylline, and this is partially reversed when the xanthine concentration in the bath is increased. From the Hill equation we obtained a value of 2 for the slope, suggesting that two molecules of aminophylline bind to the receptor. Nifedipine modifies the affinity and the intrinsic activity of aminophylline, whereas verapamil reduces its intrinsic activity. The effect of nifedipine and verapamil is explained on the basis of the changed action of aminophylline on its site as a result of the interaction of the calcium channel blockers with their interdependent receptors.

Phase I Trial of Combination Therapy with 90y Ibritumomab Tiuxetan and Gemcitabine in Patients with Non-Hodgkin's Lymphoma, Final Report.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2753-2753
Author(s):  
Hossein Borghaei ◽  
Russell J. Schilder ◽  
Samuel Litwin ◽  
Michael Millenson ◽  
Adam D Cohen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
B Cell ◽  
Research Funding ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3

Abstract Abstract 2753 Y90-ibritumomab tiuxetan radioimmuotherapy (Y90-RIT) is an effective therapy against CD20+ lymphomas approved for use in patients (pts) with relapsed/refractory low grade, follicular, or transformed B-cell non-Hodgkin's lymphoma (NHL), as well as consolidation of first remission low grade NHL. Gemcitabine (Gem) also is active against NHL and is a potent radiation sensitizer. We conducted a phase I trial to assess the safety of concomitant administration of Y90-RIT and G in patients with NHL. Eligible pts had any histologic subtype of recurrent CD20+ NHL (not candidates for potentially curative options) and met standard Y90-RIT criteria: platelets 150,000/ul; < 25% bone marrow involvement by lymphoma; prior radiation to <25% of bone marrow and no prior bone marrow or stem cell transplant. Initially, nine pts in three cohorts were treated with 250 mg/m2 of Gem IV on days 1 and 8 of the Y90-RIT treatment program (rituximab + 111In-ibritumomab day 1 and rituximab + Y90 ibritumomab day 8), with Y90-RIT at 0.2, 0.3 or 0.4 mCi/kg respectively. We confirmed that a standard Y90-RIT dose of 0.4 mg/kg can be safely administered with Gem at 250 mg/m2. In subsequent cohorts, escalating doses of Gem were used according to a Bayesian based system. Response evaluation was by CT scan criteria (IWG JCO 1999). Between 2004–2012, twenty pts were treated (10 follicular (FL), 3 marginal zone (MZL), 7 diffuse large B-cell (DLBCL) lymphomas). Median age is 71.5 (range 55–82). The median number of prior treatments is 3 (range 1–6). Gem doses ranged from 250 mg/m2 to the maximum planned dose of 800 mg/m2 on days 1 and 8. One DLT occurred (thrombocytopenia) and MTD was not reached. Treatment-related toxicities consisted of grades 3 (N=11) and 4 (N = 2) neutropenia, grade 3 (N=11) leukopenia, grades 3 (N=14) and 4 (N=8) thrombocytopenia. One grade 3 infection occurred, unrelated to study drugs. All pts recovered counts to ≤ grade 1 by week 12. The only grade 3 non-hematologic toxicity was elevated bilirubin in 1 and increased GGT in 2 pts. Best responses seen include: 3 CR/CRu, 7 PR, 4 SD, 4 PD and 2 patients still in follow up. Median PFS for all patients is 192 days. Median PFS for all non-DLBCL histologies (10 FL and 3 MALT) is 202 days and for DLBCL is 77 days. Conclusion: Standard dose Y90-RIT combined with gemcitabine days 1 and 8 is safe and well-tolerated at doses up to 800 mg/m2 in pts with relapsed/refractory NHL. Further investigation with the established doses in non-DLBCL histologies is warranted. Disclosures: Borghaei: Biogen-IDEC: Research Funding. Off Label Use: 90Y Ibritumomab Tiuxetan in relapsed DLBCL. Schilder:Biogen-IDEC: Research Funding. Smith:Biogen-IDEC: Research Funding.

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