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Jeffrey P. Callen - One of the best experts on this subject based on the ideXlab platform.
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Chlorambucil is an effective corticosteroid-sparing agent for recalcitrant pyoderma gangrenosum
Journal of the American Academy of Dermatology, 1996Co-Authors: Jyoti B. Burruss, Evan R. Farmer, Jeffrey P. CallenAbstract:Abstract Background: Pyoderma gangrenosum (PG) may fail to respond to corticosteroids. Immunosuppressive and cytotoxic agents are useful in patients with recalcitrant disease. We describe our experiences with Chlorambucil for PG. Objective: Our purpose was to evaluate the effectiveness of oral Chlorambucil in patients with PG recalcitrant to treatment with prednisone, immunosuppressive therapy, or both. Methods: Six patients with recalcitrant PG were given oral Chlorambucil 2 to 4 mg/day. Four patients were treated with a combination of prednisone and Chlorambucil, and two received Chlorambucil alone. Response was based on (1) a diminution in the size of the ulcers, or their complete healing, or (2) a decrease in the dose of corticosteroid therapy. Results: Beneficial effects were noted within 6 to 8 weeks in all six patients, and corticosteroids were eventually discontinued in all patients. Currently only two patients are still receiving Chlorambucil; the other four stopped Chlorambucil after 6 to 24 months of treatment. Their disease has remained in remission for 4 to 9 years. Relapse of disease occurred within 1 to 4 months after stopping therapy in one of the two remaining patients or reducing the dose in the other. In both patients, the disease is again responding to treatment. Minimal Chlorambucil toxicity has been noted, consisting of leukopenia in one patient. Conclusion: Our findings suggest that Chlorambucil is an effective corticosteroid-sparing agent for the control of PG.
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Chlorambucil is an effective corticosteroid-sparing agent for recalcitrant pyoderma gangrenosum.
Journal of the American Academy of Dermatology, 1996Co-Authors: Jyoti B. Burruss, Evan R. Farmer, Jeffrey P. CallenAbstract:Pyoderma gangrenosum (PG) may fail to respond to corticosteroids. Immunosuppressive and cytotoxic agents are useful in patients with recalcitrant disease. We describe our experiences with Chlorambucil for PG. Our purpose was to evaluate the effectiveness of oral Chlorambucil in patients with PG recalcitrant to treatment with prednisone, immunosuppressive therapy, or both. Six patients with recalcitrant PG were given oral Chlorambucil 2 to 4 mg/day. Four patients were treated with a combination of prednisone and Chlorambucil, and two received Chlorambucil alone. Response was based on (1) a diminution in the size of the ulcers, or their complete healing, or (2) a decrease in the dose of corticosteroid therapy. Beneficial effects were noted within 6 to 8 weeks in all six patients, and corticosteroids were eventually discontinued in all patients. Currently only two patients are still receiving Chlorambucil; the other four stopped Chlorambucil after 6 to 24 months of treatment. Their disease has remained in remission for 4 to 9 years. Relapse of disease occurred within 1 to 4 months after stopping therapy in one of the two remaining patients or reducing the dose in the other. In both patients, the disease is again responding to treatment. Minimal Chlorambucil toxicity has been noted, consisting of leukopenia in one patient. Our findings suggest that Chlorambucil is an effective corticosteroid-sparing agent for the control of PG.
Gerald M. Cohen - One of the best experts on this subject based on the ideXlab platform.
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The comparative toxicity of Chlorambucil and Chlorambucil-spermidine conjugate to BALBc mice
Cancer letters, 1994Co-Authors: Richard D. Verschoyle, Jane L. Holley, Paul M. Cullis, P. Carthew, Gerald M. CohenAbstract:The acute intraperitoneal toxicities of Chlorambucil and Chlorambucil-spermidine conjugate have been compared, in mice. Both compounds were neurotoxic and also caused a prolonged fall in bodyweight and a depletion of lymphocyte numbers associated with a fall in the total leukocyte count and loss of spleen and thymus weight. Alanine aminotransferase and aspartate aminotransferase activities and blood urea nitrogen concentration were increased at 24 h after conjugate administration, but had returned to normal at 72 h. Chlorambucil significantly decreased blood urea nitrogen concentration for 72 h, but did not affect transferase activity. Tissue concentrations of conjugate were measurable in liver and kidney for 12 days and lung for 5 days after dosing. The toxicity of both compounds was cumulative. In mol/kg, the Chlorambucil-spermidine conjugate was 10-fold more toxic than Chlorambucil, on the basis of their neurotoxicity, but only 2- to 3-fold more toxic on the basis of their effects on lymphocyte depression. The increased toxicity of the conjugate does not improve its therapeutic index relative to Chlorambucil.
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Targeting of Tumor Cells and DNA by a Chlorambucil-Spermidine Conjugate
Cancer research, 1992Co-Authors: Jane L. Holley, Andrew Mather, Richard T. Wheelhouse, Paul M. Cullis, John Hartley, John P. Bingham, Gerald M. CohenAbstract:Abstract Many tumor cells, including murine ADJ/PC6 plasmacytoma cells, possess an active energy dependent polyamine uptake system which selectively accumulates endogenous polyamines and structurally related compounds. We have attempted to target the cytotoxic drug Chlorambucil to a tumor possessing this uptake system by conjugating it to the polyamine spermidine. Furthermore, since polyamines have a high affinity for DNA, the attachment of spermidine to Chlorambucil should also facilitate its targeting to DNA. This was supported by the observation that the Chlorambucil-spermidine conjugate was approximately 10,000-fold more active than Chlorambucil at forming interstrand cross-links with naked DNA. In vitro cytotoxicity and in vivo antitumor studies were carried out using the ADJ/PC6 plasmacytoma. In vitro, using [3H]thymidine incorporation to assess cell viability following a 1-h exposure to control and polyamine depleted ADJ/PC6 cells, Chlorambucil-spermidine was 35- and 225-fold, respectively, more toxic than Chlorambucil. The increased toxicity of the conjugate compared to Chlorambucil was possibly due to enhanced DNA binding and/or facilitated uptake via the polyamine uptake system. The enhanced toxicity of the conjugate but not Chlorambucil by prior polyamine depletion with difluoromethylornithine, together with the observation that the conjugate but not Chlorambucil competitively inhibited spermidine uptake into tumor cells, supported the suggestion that the conjugate utilized the polyamine uptake system. In vivo following a single i.p. dose, the conjugate was 4-fold more potent than Chlorambucil in its ability to inhibit ADJ/PC6 tumor growth in BALB/c mice. However, the therapeutic index was not increased. Our results support the hypothesis that polyamines linked to cytotoxics facilitate their entry into tumor cells possessing a polyamine uptake system and increase their selectivity to DNA. This may have therapeutic application in the delivery of cytotoxic agents linked to polyamines to certain tumors.
Jyoti B. Burruss - One of the best experts on this subject based on the ideXlab platform.
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Chlorambucil is an effective corticosteroid-sparing agent for recalcitrant pyoderma gangrenosum
Journal of the American Academy of Dermatology, 1996Co-Authors: Jyoti B. Burruss, Evan R. Farmer, Jeffrey P. CallenAbstract:Abstract Background: Pyoderma gangrenosum (PG) may fail to respond to corticosteroids. Immunosuppressive and cytotoxic agents are useful in patients with recalcitrant disease. We describe our experiences with Chlorambucil for PG. Objective: Our purpose was to evaluate the effectiveness of oral Chlorambucil in patients with PG recalcitrant to treatment with prednisone, immunosuppressive therapy, or both. Methods: Six patients with recalcitrant PG were given oral Chlorambucil 2 to 4 mg/day. Four patients were treated with a combination of prednisone and Chlorambucil, and two received Chlorambucil alone. Response was based on (1) a diminution in the size of the ulcers, or their complete healing, or (2) a decrease in the dose of corticosteroid therapy. Results: Beneficial effects were noted within 6 to 8 weeks in all six patients, and corticosteroids were eventually discontinued in all patients. Currently only two patients are still receiving Chlorambucil; the other four stopped Chlorambucil after 6 to 24 months of treatment. Their disease has remained in remission for 4 to 9 years. Relapse of disease occurred within 1 to 4 months after stopping therapy in one of the two remaining patients or reducing the dose in the other. In both patients, the disease is again responding to treatment. Minimal Chlorambucil toxicity has been noted, consisting of leukopenia in one patient. Conclusion: Our findings suggest that Chlorambucil is an effective corticosteroid-sparing agent for the control of PG.
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Chlorambucil is an effective corticosteroid-sparing agent for recalcitrant pyoderma gangrenosum.
Journal of the American Academy of Dermatology, 1996Co-Authors: Jyoti B. Burruss, Evan R. Farmer, Jeffrey P. CallenAbstract:Pyoderma gangrenosum (PG) may fail to respond to corticosteroids. Immunosuppressive and cytotoxic agents are useful in patients with recalcitrant disease. We describe our experiences with Chlorambucil for PG. Our purpose was to evaluate the effectiveness of oral Chlorambucil in patients with PG recalcitrant to treatment with prednisone, immunosuppressive therapy, or both. Six patients with recalcitrant PG were given oral Chlorambucil 2 to 4 mg/day. Four patients were treated with a combination of prednisone and Chlorambucil, and two received Chlorambucil alone. Response was based on (1) a diminution in the size of the ulcers, or their complete healing, or (2) a decrease in the dose of corticosteroid therapy. Beneficial effects were noted within 6 to 8 weeks in all six patients, and corticosteroids were eventually discontinued in all patients. Currently only two patients are still receiving Chlorambucil; the other four stopped Chlorambucil after 6 to 24 months of treatment. Their disease has remained in remission for 4 to 9 years. Relapse of disease occurred within 1 to 4 months after stopping therapy in one of the two remaining patients or reducing the dose in the other. In both patients, the disease is again responding to treatment. Minimal Chlorambucil toxicity has been noted, consisting of leukopenia in one patient. Our findings suggest that Chlorambucil is an effective corticosteroid-sparing agent for the control of PG.
Stefan Goranov - One of the best experts on this subject based on the ideXlab platform.
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bendamustine compared with Chlorambucil in previously untreated patients with chronic lymphocytic leukaemia updated results of a randomized phase iii trial
British Journal of Haematology, 2012Co-Authors: Wolfgang Knauf, Ali Aldaoud, Anna Marina Liberati, Javier Loscertales, Raoul Herbrecht, Gunnar Juliusson, Gerhard Postner, Liana Gercheva, Toshko Lissitchkov, Stefan GoranovAbstract:The efficacy of bendamustine versus Chlorambucil in a phase III trial of previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia (CLL) was re-evaluated after a median observation time of 54months in May 2010. Overall survival (OS) was analysed for the first time. At follow-up, investigator-assessed complete response (CR) rate (21.0% vs 10.8%), median progression-free survival (21.2 vs 8.8months; P 65 years, responders and non-responders. However, patients with objective response or a CR experienced a significantly longer OS than non-responders or those without a CR. Significantly more patients on Chlorambucil progressed to second/further lines of treatment compared with those on bendamustine (78.3% vs 63.6%; P=0.004). The benefits of bendamustine over Chlorambucil were achieved without reducing quality of life. In conclusion, bendamustine is significantly more effective than Chlorambucil in previously untreated CLL patients, with the achievement of a CR or objective response appearing to prolong OS. Bendamustine should be considered as a preferred first-line option over Chlorambucil for CLL patients ineligible for fludarabine, cyclophosphamide and rituximab. (Less)
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phase iii randomized study of bendamustine compared with Chlorambucil in previously untreated patients with chronic lymphocytic leukemia
Journal of Clinical Oncology, 2009Co-Authors: Wolfgang Knauf, Toshko Lissichkov, Ali Aldaoud, Anna Marina Liberati, Javier Loscertales, Raoul Herbrecht, Gunnar Juliusson, Gerhard Postner, Liana Gercheva, Stefan GoranovAbstract:PURPOSE: This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and Chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL). PATIENTS AND METHODS: Patients (Chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee. RESULTS: A total of 319 patients were randomly assigned (162 bendamustine, 157 Chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 Chlorambucil-treated patients (P < .0001). More patients showed complete responses with bendamustine than with Chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with Chlorambucil (P < .0001). Bendamustine was also associated with an improvement in duration of remission, compared with Chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with Chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of Chlorambucil-treated patients. CONCLUSION: Bendamustine offers significantly greater efficacy than Chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.
Chang-sue Yang - One of the best experts on this subject based on the ideXlab platform.
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Chlorambucil Therapy in Sympathetic Ophthalmia
American Journal of Ophthalmology, 1995Co-Authors: Chang-sue YangAbstract:Purpose We used Chlorambucil therapy in a 28-year-old man with sympathetic ophthalmia, which was incompletely controlled with systemic corticosteroids, and the patient developed serious side effects. Methods The patient sustained a penetrating injury with an intraocular metal foreign body. Attempts to remove it with a magnet failed. Vitrectomy with lensectomy successfully removed the intraocular foreign body. Five weeks after the injury and one week after the vitrectomy, sympathetic ophthalmia developed, with severe visual impairment and inflammation and serous retinal detachment in the fellow eye. Sympathetic ophthalmia was poorly responsive to topical cycloplegics, topical corticosteroids, and systemic corticosteroid therapy. The patient developed side effects to the corticosteroids, which were reduced to prednisolone 60 mg daily. Chlorambucil therapy was begun at 2 mg daily, increased by 2 mg per day each week to the maximum of 8 to 12 mg per day. The total dose of Chlorambucil was 793 mg; the duration of therapy was 23 weeks. Results Successful treatment was achieved with Chlorambucil therapy. There was clinical remission of inflammation and absorption of exudative retinal detachment. The neurosensory retina sealed down; the retinal pigment epithelium demonstrated severe destruction, with the characteristic sunset-glow and moth-eaten appearance. No malignancy and no serious side effect developed during one year of follow-up. After termination of therapy, the patient had sustained remission of ocular disease. Conclusion Chlorambucil immunosuppressive therapy is an alternative to corticosteroids for the treatment of corticosteroid-resistant sympathetic ophthalmia; however, because Chlorambucil has potentially serious late side effects, prolonged follow-up is necessary.