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PubMed2000

Cyclophosphamide and water retention: mechanism revisited.

We describe an 8 year-old girl with established diabetes insipidus who developed cyclophosphamide-associated antidiuresis. The patient had received cyclophosphamide as part of a high-dose chemotherapy regimen for recurrent suprasellar dysgerminoma prior to autologous bone marrow transplantation. Urinary output decreased and specific gravity increased shortly after a 1 hour i.v. infusion of 50 mg/kg cyclophosphamide and the effect lasted some 5 hours. No other drug could be implicated. This response, occurring in a patient with no ability to secrete vasopressin, suggests a direct tubular effect of one or more cyclophosphamide metabolites. Administering i.v. cyclophosphamide requires careful monitoring of fluid balance in order to avoid water intoxication. Further research is warranted both into the mechanism of this effect and the metabolite responsible for it.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

A theoretical study of H3PO4, nor-N-mustard, and cyclophosphamide.

Some physical and chemical properties of the cancerostat cyclophosphamide (generic name: ENDOXAN) and its basic constituents H3PO4 and nor-N-mustard have been calculated with the help of a modified CNDO/S-method. The spectroscopic data of the H3PO4, which is the starting-point for a corresponding calculation of cyclophosphamide, has been studied by taking account of the 3 d electron of the phosphorus. Nor-N-mustard is a very reactive compound, characterized by the ability to split off chloride ions and to act as an alkylating agent. The binding of the nor-N-mustard to the cyclic phosphate ester (cyclophosphamide) modifies the chemical reactivity of the mustard group in an essential way, and the 3 d electron of the phosphorus plays an important role with respect to the excitability of the C--Cl bonds. Cyclophosphamide must be metabolized in a suitable way to develop the same alkylating activity as the nor-N-mustard. The computation of the excited states of cyclophosphamide revealed a similar term scheme as it was found by Clar in the case of the carcinogenic polycyclic hydrocarbons.

Cyclophosphamide↗

PubMed2002

Left ventricular diastolic dysfunction induced by cyclophosphamide in blood stem cell transplantation.

Cardiac complications are major limiting factors regarding the success of high-dose chemotherapy supported by blood stem cell transplantation (BSCT). The cardiotoxicity of cyclophosphamide remains obscure relative to that of anthracyclines. The aim of this study was to estimate noninvasively the cardiotoxicity of cyclophosphamide administered during the pretransplant conditioning of BSCT for patients with various hematological diseases. A total of 27 consecutive patients were divided into two groups depending on the conditioning regimen, ie, group A (n=15) which received cyclophosphamide (median dose of 120 mg/kg; range 100 to 200 mg/kg) and group B (n=12) which did not. Ultrasound cardiograms (UCG) and signal-averaged electrocardiograms (SAECG) were recorded in the two groups both preceding and following the BSCT. There were no statistical intergroup or intragroup differences in left ventricular (LV) dimensions or contractile function. Significant (P<0.01) posttransplant increases in interventricular septal wall thickness and Ap/Ep ratio were noted in group A. Moreover, the filtered QRS duration as estimated by SAECG was prolonged (P<0.05) whereas the summated LV voltage (S(V1)+R(V5)) was reduced in the posttransplant period only in group A. These results suggest that early cyclophosphamide cardiotoxicity was characterized by LV diastolic rather than systolic dysfunction. These findings may contribute to acute hemodynamic deterioration observed after cyclophosphamide-containing conditioning chemotherapy.

Adolescent↗

PubMed2004

Cyclophosphamide in the treatment of focal segmental glomerulosclerosis.

Prednisone is the initial treatment of primary focal segmental glomerulosclerosis. However, when immunosuppressive agents in combination with steroids are used in the treatment of prednisone-dependent and prednisone-resistant patients the remission rate is variable. We report a long-term trial using cyclophosphamide (2.0 to 3.0 mg/kg body weight for 12 weeks) in combination with prednisone (1.0 to 2.0 mg/kg body weight), as compared with prednisone alone for the treatment of prednisone-resistant and frequently relapsing nephrotic syndrome and focal segmental glomerulosclerosis. Fifty-four patients (34 males and 20 females) with a diagnosis of idiopathic nephrotic syndrome and focal segmental glomerulosclerosis, followed-up for an average of 86.1 +/- 82.4 months, were evaluated. Complete remission occurred in 20.4% and partial remission in 14.8% of the patients treated with steroids and in 26.7 and 20.0% of the patients treated with cyclophosphamide + prednisone, respectively. Of the 24 prednisone-resistant patients treated with steroids in combination with cyclophosphamide, 33.3% obtained a complete/partial response. At the time of final evaluation, 25% of the patients treated with prednisone and 10.0% of those treated with prednisone in combination with cyclophosphamide had reached end-stage renal disease. Persistent nephrotic syndrome and progressive renal insufficiency were more frequently observed among the patients treated with prednisone alone (50.0 vs 33.3% and 33.3 vs 16.7%, respectively). The treatments were well tolerated and no patient experienced adverse reactions requiring discontinuation of medications. Although open-label and non-randomized, the present trial showed that cyclophosphamide is a reasonable choice for the treatment of primary focal segmental glomerulosclerosis and prednisone-resistant nephrotic syndrome.

Adolescent↗

PubMed2005

Cyclophosphamide and immunoadsorption apheresis treatment of lupus nephritis nonresponsive to drug therapy alone.

In this report we present a 28-year-old male patient with systemic lupus erythematosus (SLE) that was treated with immunoadsorption apheresis (IA) and cyclophosphamide for lupus nephritis (proliferative glomerulonephritis, class IV-B) after proving nonresponsive to drug therapy alone. Before starting the therapeutic cycle with IA, the patient was administered prednisone 25 mg/d, hydroxychloroquine 200mg twice/d, ACE inhibitors 5 mg/d, aspirin 100 mg/d, furosemide 50 mg/d, and intravenous (IV) albumin (20%) 50 mL. Deteriorating clinical conditions necessitated a renal biopsy, and thereafter an increase in medication. The patient was given a bolus of IV cyclophosphamide 1 g/d for 1 day and IV methylprednisone 500 mg/d for 3 days. This was not followed by any improvement and the renal functions worsened. Thus, 3 weeks after the more aggressive pharmacologic treatment with cyclophosphamide, which had been prescribed to improve renal function, and given the young age of the patient, the decision was made to administer IA (Selesorb). IA selectively removes IgG and IgM immune complexes from the plasma, thereby reducing the complications induced by the pathogenic autoimmune reaction. The treatment was administrated twice a week for the first 15 days, once a week for a further 5 weeks, and biweekly in the last month with a bolus of cyclophosphamide (average 250-100 mg) after each session. After twelve sessions of IA over 3 months, renal function was completely restored and the patient discharged. Although it is not proven, the concomitant use of cyclophosphamide could presumably improve the final clinical outcome.

Adult↗

PubMed1998

A phase I trial of standard and cyclophosphamide dose-escalated CHOP with granulocyte colony stimulating factor in elderly patients with non-Hodgkin's lymphoma.

The purpose of this study was to assess the safety and feasibility of using standard and escalated doses of cyclophosphamide with doxorubicin, vincristine and prednisone (CHOP) plus granulocyte colony stimulating factor (G-CSF) to treat elderly patients who have advanced stage intermediate grade lymphoma. Consenting patients age > or = 65 years who had an acceptable performance status and adequate cardiac, renal and liver function were eligible for this Phase I study. G-CSF, 5 ug per kg, was given daily with each cycle from day 2 until neutrophil recovery of > or = 10 x 10(9)/L. Ten patients received standard CHOP; sequential cohorts of 5 patients were then to be given CHOP with cyclophosphamide doses of 900, 1050, 1200, and 1350 mg/m2. If 2 patients had dose limiting toxicity, cohorts were expanded to 10 patients; if 3 patients within a cohort had dose limiting toxicity, the previous dose level was considered the maximum tolerated dose of cyclophosphamide. Secondary outcomes were average relative received dose intensity, response, progression-free and overall survival, toxicity, hospitalizations and transfusions. Eight patients (80%) completed 6 cycles of standard CHOP plus G-CSF. Therapy was stopped prematurely in 2 patients due to pneumonia (1) and disease progression (1). Six of 11 patients (55%) given CHOP with cyclophosphamide 900 mg/m2 (CHOP-900) completed treatment. Therapy was stopped in 5 patients due to a toxic death from infection (1), cumulative fatigue (3), and pneumonitis (1). Further dose escalations were not attempted due to the inability to complete 6 treatment cycles in 45% of CHOP-900 cases. The received dose intensities of cyclophosphamide relative to standard CHOP measured over the actual time on therapy were 96% with standard CHOP and 115% with CHOP-900. At 3 years, progression free survival is 40% with standard CHOP and 82% with CHOP-900; overall survivals are 40% and 91% respectively. Neutropenia of < 1.0 x 10(9)/L occurred in 47% of treatment cycles with standard CHOP and in 77% with CHOP-900. In both groups, the mean duration of neutropenia was < 2 days. From these studies we conclude that, standard CHOP with G-CSF can be safely given to elderly patients. Escalating the dose of cyclophos

Aged↗

PubMed1991

Sustained remission of membranous glomerulonephritis after cyclophosphamide and prednisone.

OBJECTIVE: To determine the effect of cyclophosphamide and prednisone on progressive renal failure and on nephrotic features in patients with membranous glomerulonephritis. DESIGN: Prospective, nonrandomized time series. SETTING: Outpatient clinic at a university medical center. PATIENTS: Eleven consecutive patients with biopsy-proven membranous glomerulonephritis and rising plasma creatinine levels over at least 6 months. INTERVENTION: Cyclophosphamide and prednisone in ten patients and cyclophosphamide alone in one patient. MEASUREMENTS AND MAIN RESULTS: In ten patients treated with both agents, the median plasma creatinine rose 53 mumol/L (0.6 mg/dL) over the months before treatment from 141 to 194 mumol/L (1.6 to 2.2 mg/dL) (95% CI, 27 to 141 mumol/L; P = 0.002). After combined therapy for 6 months, the median plasma creatinine fell to 133 mumol/L (1.5 mg/dL) for a median decline of 62 mumol/L (0.7 mg/dL) (CI, 44 to 150 mumol/L; P = 0.006). Pretreatment plasma creatinine levels, which ranged from 159 to 371 mumol/L (1.8 to 4.2 mg/dL), decreased in the ten patients by 6 months and remained stable in seven of the eight patients followed 24 to 54 months after therapy was completed. The median urine protein excretion decreased by 9.6 g/d with 12 months of therapy in the ten patients from 11.9 to 2.3 g/d (CI, 6.0 to 15.1 g/d; P less than 0.001). The median plasma albumin rose by 14 g/L from 24 to 38 g/L (CI, 11 to 19 g/L; P less than 0.001). The median plasma cholesterol fell by 3.26 mumol/L (140 mg/dL) from 10.45 to 6.52 mumol/L (405 to 252 mg/dL) (CI, 1.42 to 7.16 mumol/L; P = 0.01). One patient who had a relapse 30 months after completing therapy responded to re-treatment with renal function and nephrotic variables returning toward normal. The eleventh patient received cyclophosphamide alone and had a course similar to that of the combined therapy group. CONCLUSION: Cyclophosphamide plus prednisone can promote prolonged remissions in membranous glomerulonephritis even when renal function is already declining.

Adult↗

PubMed1993

Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy.

OBJECTIVE: To determine the risk for secondary amenorrhea after pulse cyclophosphamide therapy in premenopausal women with systemic lupus erythematosus. DESIGN: Controlled, retrospective clinical study. SETTING: Government referral-based research hospital. PATIENTS: Thirty-nine women younger than 40 years treated with pulse cyclophosphamide therapy for active lupus nephritis or neuropsychiatric lupus. Sixteen women who received pulses of intravenous methylprednisolone were controls. INTERVENTIONS: Sixteen patients received pulse cyclophosphamide (0.5 to 1.0 g/m2 body surface area) monthly for a total of 7 doses (short-CY), and 23 patients received 15 or more doses (long-CY). Control patients were treated with monthly pulses of methylprednisolone (1.0 g/m2) for a total of nine doses. MEASUREMENTS: Rates of amenorrhea were evaluated according to duration of treatment (number of doses) and age at the initiation of pulse therapy. RESULTS: Two of 16 patients (12%) in the Short-CY group and 9 of 23 (39%) in the long-CY group developed sustained amenorrhea (P = 0.07). Rates of sustained amenorrhea (short- and long-CY) according to age at the start of pulse therapy were: < or = 25 years, 2/16 (12%); 26 to 30 years, 4/15 (27%); > or = 31 years, 5/8 (62%) (P = 0.04). The increased risk for sustained amenorrhea in patients treated with long-CY was most evident in patients older than 25 years (short-CY [2/12] compared with long-CY [7/11]; P = 0.03). Three other patients with short-CY had reversal of amenorrhea fewer than 12 months after cessation of therapy. Amenorrhea was not observed in any of the 16 control patients. CONCLUSIONS: Intermittent pulse cyclophosphamide therapy in patients with systemic lupus erythematosus is associated with sustained amenorrhea, which is related to both age and number of doses of cyclophosphamide.

Adult↗

PubMed1998

Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease.

BACKGROUND: Immunoablative high-dose cyclophosphamide without stem-cell rescue induces durable, complete remission in most patients with aplastic anemia. OBJECTIVE: To determine the efficacy of high-dose cyclophosphamide in various refractory, severe autoimmune diseases. DESIGN: Prospective phase II study. SETTING: Johns Hopkins University (Baltimore, Maryland) and Hahnemann University (Philadelphia, Pennsylvania). PATIENTS: Eight patients with refractory, severe autoimmune disease. INTERVENTION: Immunoablative high-dose cyclophosphamide (50 mg/kg of body weight per day) for 4 consecutive days. MEASUREMENTS: Clinical and laboratory variables of autoimmune disease. RESULTS: Seven patients improved markedly: Five achieved complete remission and two achieved partial remission. Four patients have remained in continuous complete remission for 3 to 21 months, and two patients in partial remission continue to improve after 14 and 19 months of follow-up. High-dose cyclophosphamide was well tolerated; median times to a neutrophil count of 0.5 x 10(9) cells/L and platelet transfusion independence were 17 and 16 days, respectively. CONCLUSIONS: Immunoablative high-dose cyclophosphamide without stem-cell rescue can induce complete remission in patients with refractory, severe autoimmune disease. Reemergence of marrow function is similar to that seen after autologous transplantation and does not carry the risk for reinfusion of autoaggressive lymphocytes with the autograft.

Adult↗

PubMed2000

Cyclophosphamide is associated with pulmonary function and survival benefit in patients with scleroderma and alveolitis.

BACKGROUND: Lung inflammation (alveolitis) may cause lung fibrosis in scleroderma. OBJECTIVE: To determine whether cyclophosphamide treatment is associated with retention of lung function and improved survival in scleroderma patients with alveolitis. DESIGN: Retrospective cohort study. SETTING: Johns Hopkins and University of Maryland Scleroderma Center. PATIENTS: 103 patients with scleroderma who had bronchoalveolar lavage or lung biopsy. INTERVENTION: Cyclophosphamide therapy. MEASUREMENTS: 1) Serial measurement of forced vital capacity (FVC) and carbon monoxide diffusing capacity and 2) survival. RESULTS: During a median follow-up of 13 months after bronchoalveolar lavage or biopsy, patients with alveolitis who did not receive cyclophosphamide therapy experienced a decrease in FVC (mean difference, -0.28 L [95% Cl, -0.41 to -0.16 L] and -7.1% of the predicted value [Cl, -10.9% to -4.0%]). Carbon monoxide diffusing capacity also decreased in these patients (mean difference, -3.3 x mmol min(-1) x kPa(-1) [Cl, -4.6 to -2.1 mmol x min(-1) x kPa(-1)] and -9.6% of the predicted value [Cl, -16.7% to -2.4%]). During a median follow-up of 16 months, patients with alveolitis who received cyclophosphamide were more likely to have a good outcome (stabilization or improvement) in FVC (relative risk, 2.5 [Cl, 1.5 to 4.1]) and diffusing capacity (relative risk, 1.5 [Cl, 1.0 to 2.2]). These patients also had improved survival; the median survival rate was 89% (25th, 75th percentiles, 84%, 94%) compared with 71% (25th, 75th percentiles, 55%, 86%) in untreated patients (P = 0.01, log-rank test). CONCLUSIONS: The presence of lung inflammation identifies patients with scleroderma who are more likely to have worsening lung function. Lung function outcomes and survival are improved in patients with alveolitis who receive cyclophosphamide.

Biopsy↗

PubMed2001

Durable treatment-free remission after high-dose cyclophosphamide therapy for previously untreated severe aplastic anemia.

BACKGROUND: Severe aplastic anemia is a life-threatening bone marrow failure disorder. High-dose cyclophosphamide therapy followed by allogeneic bone marrow transplantation cures the disease. However, it requires a suitable donor and carries the risk for graft-versus-host disease. A small pilot study demonstrated that high-dose cyclophosphamide therapy without bone marrow transplantation leads to durable, treatment-free complete remission. OBJECTIVE: To confirm the safety and efficacy of high-dose cyclophosphamide therapy alone in patients with severe aplastic anemia. DESIGN: Uncontrolled clinical trial. SETTING: Three tertiary care hospitals. PATIENTS: 19 patients with untreated severe aplastic anemia. INTERVENTION: Cyclophosphamide, 50 mg/kg of body weight per day for 4 consecutive days. MEASUREMENTS: Probability of response and overall survival were measured. Complete remission was defined as normal blood count for age and sex. Partial remission was defined as independence from transfusion and an absolute neutrophil count greater than 0.5 x 10(9) cells/L without growth factor support. Nonresponders were patients who remained transfusion dependent or died. Relapse was defined as no longer meeting criteria for partial or complete remission. RESULTS: The median time to an absolute neutrophil count of 0.5 x 10(9) cells/L was 49 days. The probability of survival was 84% (95% CI, 59% to 95%) at 24 months. The probability of achieving treatment-free remission was 73% (CI, 51% to 91%) at 24 months, and the probability of achieving complete remission was 65% (CI, 39% to 89%) at 50 months. No responding patients have had relapse or have developed secondary clonal disorders. CONCLUSIONS: High-dose cyclophosphamide therapy without bone marrow transplantation produces durable treatment-free remission in severe aplastic anemia. This approach deserves further study in patients with severe aplastic anemia who are not suitable candidates for allogeneic bone marrow transplantation.

Adolescent↗

PubMed1979

Cyclophosphamide in the management of advanced Graves' ophthalmopathy. A preliminary report.

Three patients with advanced Graves' ophthalmopathy were treated with cyclophosphamide. All had proptosis and diplopia. One patient had disabling iatrogenic Cushing's syndrome from steroid treatment of the ophthalmopathy and had undergone bilateral orbital decompression before cyclophosphamide therapy; steroids could not subsequently be withdrawn. When cyclophosphamide was administered to the cushingoid patient, withdrawal of glucocorticoid therapy was then possible. Diplopia completely resolved in two patients and improved in the third coincident with administration of cyclophosphamide. Deteriorating visual acuity resolved in one patient. Chemosis improved in the two affected patients. Proptosis was unchanged in all three patients. Cyclophosphamide deserves further study as a therapeutic agent in Graves' disease.

Administration, Oral↗

PubMed1999

The effect of melatonin application on lipid peroxidation during cyclophosphamide therapy in female rats.

OBJECTIVE: Our purpose was to investigate whether melatonin has any protective effect against lipid peroxidation induced by cyclophosphamide. MATERIAL AND METHODS: We used an animal model to study the effect of melatonin. Fifteen female Wistar rats (180-200 gram in weight) were randomly assigned to three different groups. Group 1 (n = 5) received saline injections as a control. Group 2 (n = 5) received cyclophosphamide. Group 3 (n = 5) received cyclophosphamide + melatonin. The animals were sacrificed two hours after cyclophosphamide administration and blood samples were taken and used for assaying superoxide dismutase (SOD) activity, glutathione peroxidase (GP) activity for the antioxidative enzymes, and malondialdehyde (MDA) level as an index of lipid peroxidation. RESULTS: MDA levels were more increased in the second group compared with the control group (p < 0.01). In the third group, they were significantly lower than in the second group (p < 0.05). SOD and GP activities were found to be decreased significantly in the second group compared with the control group (p < 0.05 and p < 0.01, respectively). They were found to be elevated in the third group compared with the second group (p > 0.05 and p < 0.05, respectively). CONCLUSIONS: The above results suggest that melatonin has a protective role in cyclophosphamide induced lipid peroxidation in rats. Besides scavenging the highly toxic free radicals, melatonin also stimulates the antioxidant enzyme activity of GP.

Animals↗

PubMed1999

Protective effect of the antioxidant stobadine against cyclophosphamide and irradiation induced oxidative stress.

The antioxidant stobadine was tested for its efficiency against oxidative stress in model experiments with ICR nonpregnant mice exposed either to cyclophosphamide (80 mg/kg) or whole body 60Co (6.5 Gy) irradiation. In a teratological experiment, pregnant mice were exposed to cyclophosphamide (10 mg/kg) from day 11 to 17 of gestation. Toxicity was measured by determining the lysosomal enzymes acid phosphatase and N-acetyl-beta-D-glucosaminidase. Cyclophosphamide and irradiation caused a significant increase in acid phosphatase and N-acetyl-beta-D-glucosaminidase activity in the spleen of nonpregnant mice. In the liver, lysosomal enzyme activities were unchanged and no changes in protein levels were recorded. In pregnant mice, acid phosphatase and N-acetyl-beta-D-glucosaminidase activities were increased in the spleen. An increase in foetal acid phosphatase liver activity was found. Pretreatment with stobadine prior to cyclophosphamide and irradiation significantly diminished the biochemical changes in both nonpregnant and pregnant mice. We conclude that stobadine is able to protect mice against cyclophosphamide- or irradiation-induced oxidative stress.

Acetylglucosaminidase↗

PubMed1975

Pure red cell aplasia (PRCA): Response of three patients of cyclophosphamide and/or antilymphocyte globulin (ALG) and demonstration of two types of serum IgG inhibitors to erythropoiesis.

Three cases of adult pure red cell aplasia (PRCA) ARE REPORTED. All patients proved refractory to various combinations of androgens and corticosteroids. The first case, harboring a thymoma, showed a complete clinical remission following cyclophosphamide therapy. The second and third responded similarly to either a combined cyclophosphamide + antilymphocyte globulin (ALG) treatment or to ALG administration preceded by a small dosage of cyclophosphamide, which had proved ineffective when administered alone. Serum IgG inhibitors to erythropoiesis were demonstrated in all cases by means of in vivo and/or in vitro techniques. The inhibitor(s), although directed against the erythroid marrow in both the first and third patients (PRCA type A), apparently functioned as an antibody to circulating erythropoientin (Ep) in the second case (PRCA type B). The inhibitor(s) was always absent in postremission samples. Additionally, experimental models for both types of human PRCA were established in normal rodents. The present studies support the contention that adult PRCA is an autoimmune disease. The therapeutic role of cytotoxic-immunodepressive agents in PRCA patients is confirmed. It is emphasized that ALG may represent an additional therapeutic tool in cases resistant to cyclophosphamide and/or steroids. In addition, cyclophosphamide proved effective in a patient harboring a thymoma not amenable to surgery. Finally, it is postulated that IgG serum autoantibodies, directed against either an early erythroid precursor (PRCA type A) or, more rarely, circulating Ep (PRCA type B), play a major role in the pathogenesis of the disease.

Aged↗

PubMed1975

Cyclophosphamide therapy for rheumatoid arthritis.

Cyclophosphamide in high doses was given for six months to 19 patients with rheumatoid arthritis. A second group of patients with rheumatoid arthritis whose conditions were stable on low-dose prednisone received in addition either cyclophosphamide or placebo for six months. Measurements of joint function and joint inflammation were used to estimate disease activity. Joint inflammation progressively decreased and joint function improved in the high-dose group. The low-dose cyclophosphamide-plus-prednisone group had a similar response that was different from the prednisone-plus-placebo group. Cyclophosphamide toxicity was common in the high-dose group and minimal in the low-dose-plus-prednisone group. Cyclophosphamide therapy improved the arthritis of these patients. The results were almost as good in the low-dose-plus-prednisone group, and the toxicity was much less.

Administration, Oral↗

PubMed1975

[Potentiation of the antitumor action of cyclophosphamide with a change in the cell population makeup and an increase in cellular permeability].

Cells of Ehrlich ascites tumor survived after cyclophosphamide injection showed no multiplication during 48 hours. As a result, vinblastine injection simultaneously with cyclophosphamide or following 24 hours produced no additional death of cells. The administration of cyclophosphamide 6 hours after vinblastine resulted in the death of cells 30 times as much as in the injection of both substances simultaneously. Synergism was due to the disappearance of cells in phase G from the population, which are resistant to cyclophosphamide. Tween 80 enhanced an antitumor effect of cyclophosphamide without increasing the toxicity.

Animals↗

PubMed1992

Treatment of pemphigus vulgaris with pulse intravenous cyclophosphamide.

BACKGROUND: Although corticosteroids have dramatically altered the prognosis in pemphigus vulgaris, morbidity and mortality from systemic corticosteroid side effects remains high. While immunosuppressive agents have been successfully used in pemphigus vulgaris, there is a high incidence of side effects with these agents as well. Particularly bothersome are reports of increased risk of malignancy with long-term use of immunosuppressive agents. For these reasons, we used a protocol that includes low-dose oral cyclophosphamide coupled with pulse intravenous cyclophosphamide in two patients with recalcitrant pemphigus vulgaris. OBSERVATIONS: Both patients responded well to monthly doses of intravenous cyclophosphamide with rapid decrease in the frequency and severity of blistering, resulting in resolution of their disease after 7 and 10 months, respectively. CONCLUSIONS: Pulse doses of immunosuppressive agents appear to be successful in the treatment of pemphigus vulgaris. High-dose steroid therapy can be tapered with the use of this treatment. Because monthly intravenous doses of cyclophosphamide lead to a substantially reduced cumulative dose, when compared with standard oral regimens, the risk of developing malignancy may also be reduced. Further studies using larger groups of patients are needed to evaluate the efficacy of pulse intravenous cyclophosphamide in pemphigus vulgaris. Long-term follow up will be necessary to compare the incidence of malignancy in patients receiving pulse doses of immunosuppressive agents with that in patients receiving continuous oral treatment.

Adult↗