SEARCH · PubMed Health

Results for “CYCLOPHOSPHAMIDE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 775 records · Page 43Linked to original sources

PubMed1994

A prospective, randomized comparison of cyclophosphamide and azathioprine for early rejection prophylaxis after cardiac transplantation. Decreased sensitization to OKT3.

Humoral immune responses have been implicated in the pathogenesis of vascular rejection, allograft coronary artery disease, and sensitization to OKT3. Because cyclophosphamide (CP) is a potent suppressor of humoral immunity, we postulated that substituting cyclophosphamide for azathioprine (AZA) would be associated with a decrease in acute vascular rejection and sensitization to OKT3 in cardiac transplant recipients also receiving cyclosporine, corticosteroids, and perioperative OKT3. We prospectively randomized 119 patients to receive azathioprine (n = 61) or cyclophosphamide (n = 58) from the time of transplantation. Dosage was adjusted to target white blood cell (WBC) counts. At six weeks posttransplantation, cyclophosphamide was converted to azathioprine. Patients were followed for a mean of 321 +/- 16 days. At four weeks WBC (1000/mm3) was 9.2 +/- 0.4 (SEM) in the AZA group and 9.7 +/- 0.6 for the CP group (P = 0.4). No differences were noted between the CP and AZA groups in mean cellular grades of rejection (1.8 +/- 0.1 vs. 1.7 +/- 0.1), mean vascular grades of rejection (2.0 +/- 0.1 vs. 1.8 +/- 0.1), early treated rejection episodes (1.9 +/- 0.1 vs. 2.2 +/- 0.1) days to first treated cellular rejection (38 +/- 3 vs. 41 +/- 3), or the number of patients manifesting primarily vascular rejection (18 vs. 19). Major infections and survival did not differ between the two groups. Eight patients in the AZA group developed anti-OKT3 antibodies, whereas only one patient in the CP group did (P = 0.04). In the early posttransplant period cyclophosphamide decreases the incidence of sensitization to OKT3 and appears to be as effective as azathioprine in preventing both cellular and vascular rejection.

Antibody Formation↗

PubMed1994

Involvement of human glutathione S-transferase isoenzymes in the conjugation of cyclophosphamide metabolites with glutathione.

Alkylating agents can be detoxified by conjugation with glutathione (GSH). One of the physiological significances of this lies in the observation that cancer cells resistant to the cytotoxic effects of alkylating agents have higher levels of GSH and high glutathione S-transferase (GST) activity. However, little is known about the GSH-/GST-dependent biotransformation of alkylating agents, including cyclophosphamide. Cyclophosphamide becomes cytostatic after the enzymatic formation of 4-hydroxycyclophosphamide. The ultimate alkylating species formed from cyclophosphamide is phosphoramide mustard. In this paper we describe the involvement of purified human glutathione S-transferases isoenzymes GST A1-1, A2-2, M1a-1a, and P1-1 in the formation of two types of glutathionyl conjugates of cyclophosphamide, i.e., 4-glutathionylcyclophosphamide (4-GSCP) and monochloromonoglutathionylphosphoramide mustard. When 0.1 mM 4-hydroxycyclophosphamide and 1 mM GSH was incubated in the presence of 10 microM GST A1-1, A2-2, M1a-1a, and P1-1 the formation of 4-GSCP was 2-4-fold increased above the spontaneous level. Enzyme kinetic analysis demonstrated the lowest Km (0.35 mM) for GST A1-1. Km values for the other GST enzymes ranged from 1.0 to 1.9 mM. Glutathione S-transferase A1-1 (40 microM) also increased the conjugation of phosphoramide mustard and GSH (both 1 mM) 2-fold, while the other major human isoenzymes, A2-2, M1a-1a, and P1-1, did not influence the formation of monochloromonoglutathionylphosphoramide mustard. These results indicate that only one enzyme within the class of human GST alpha enzymes was able to catalyze the reaction of the aziridinium ion of phosphoramide mustard with glutathione. Thus increased levels of GST A1-1 in tumor cells can contribute to an enhanced detoxification of phosphoramide mustard and hence to the development of drug resistance. Since all of the human GSTs tested did catalyze the formation of 4-GSCP, the role of 4-GSCP either as a transport form of activated cyclophosphamide or as a detoxification product is discussed.

Biotransformation↗

PubMed1976

Effect of centrophenoxine on cyclophosphamide concentration in blood.

In order to clarify the mechanism of potentiation of cyclophosphamide activity by centrophenoxine, blood concentration of total and activated cyclophosphamide was examined. Blood concentration of cyclophosphamide increased by the compound and biological half-life of activated cyclophosphamide was markedly increased to 30 min from 18 min in intraperitoneal administration. At the same time, concentration of active form in ascites fluid was also increased and biological half-life of the active form was increased to 50 min from 18 min. Similar increase in blood level of active form was also shown by p-chlorophenoxyacetic acid and probenecid, but concentrations at early stages after injection was not increased. As a result, potentiation of cyclophosphamide activity by centrophenoxine was found to be due to maintenance of active form in both blood and ascites fluid at higher levels than those in the control.

Acetates↗

PubMed1994

Treatment of severe refractory uveitis with intravenous cyclophosphamide.

OBJECTIVE: We assessed the efficacy of intravenous (iv) cyclophosphamide therapy for patients with uveitis. METHODS: Eleven patients with uveitis were treated with iv cyclophosphamide. Patients were from a tertiary care, referral practice, had failed oral corticosteroid therapy, and had disease that interfered with activities of daily living. RESULTS: Only 5 patients benefitted and the improvement was sustained without additional immunosuppression in only 2 patients, one of whom had only mild eye disease and was receiving cyclophosphamide for a central nervous system vasculitis. Four patients worsened during the therapy. CONCLUSION: Although iv cyclophosphamide may have fewer risks than daily, oral cyclophosphamide, the majority of patients with uveitis do not experience a sustained benefit from this therapeutic approach.

Adult↗

PubMed1996

Complete remission in severe aplastic anemia after high-dose cyclophosphamide without bone marrow transplantation.

Severe aplastic anemia (SAA) can be successfully treated with allogeneic bone marrow transplantation (BMT) or immunosuppressive therapy. However, the majority of patients with SAA are not eligible for BMT because they lack an HLA-identical sibling. Conventional immunosuppressive therapy also has major limitations; many of its remissions are incomplete and relapse or secondary clonal disease is common. Cyclophosphamide is a potent immunosuppressive agent that is used in all BMT conditioning regimens for patients with SAA. Preliminary evidence suggested that high-dose cyclophosphamide, even without BMT, may be beneficial to patients with SAA. Therefore, 10 patients with SAA and lacking an HLA-identical sibling were treated with high-dose cyclophosphamide (45 mg/kg/d) for 4 consecutive days with or without cyclosporine. A complete response (hemoglobin level, > 13 g/dL; absolute neutrophil count, > 1.5 x 10(9)/L, and platelet count > 125 x 10(9)/L) was achieved in 7 of the 10 patients. One of the complete responders died from the acquired immunodeficiency syndrome 44 months after treatment with high-dose cyclophosphamide. The 6 remaining patients are alive and in continuous complete remission, with a median follow-up of 10.8 years (range, 7.3 to 17.8 years). The median time to last platelet transfusion and time to 0.5 x 10(9) neutrophils/L were 85 and 95 days, respectively. None of the complete responders has relapsed or developed a clonal disease. These results suggest that high-dose cyclophosphamide, even without BMT, may be more effective than conventional immunosuppressive therapy in restoring normal hematopoiesis and preventing relapse or secondary clonal disorders. Hence, further studies confirming the efficacy of this approach in SAA are indicated.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Paclitaxel couplets with cyclophosphamide or cisplatin in metastatic breast cancer.

Determining active combinations containing paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) to treat metastatic breast cancer has been the focus of recent clinical development. Paclitaxel combined with either cyclophosphamide or cisplatin has several potential advantages: cisplatin and cyclophosphamide are active single agents against previously untreated metastatic breast cancer, colony-stimulating factors can modulate overlapping toxicities like myelosuppression, and no mechanisms of cross-resistance between paclitaxel and these agents are yet known. Major questions include the optimal schedule of administration and the sequence dependence of toxicities with these combinations. Paclitaxel schedules with cisplatin include either two dose levels using the 24-hour infusion or a novel biweekly 3-hour infusion. The sequence in the three available studies was paclitaxel followed by cisplatin. Hematologic toxicities were dose limiting with the biweekly and low-dose 24-hour paclitaxel/cisplatin combinations; with granulocyte colony-stimulating factor, neurotoxicity became a prominent cumulative toxicity of the high-dose paclitaxel/cisplatin combination. Response rates in the first-line treatment of metastatic breast cancer ranged from 49% to 85%. In the three completed studies with cyclophosphamide, paclitaxel has been administered over either 72, 24, or 3 hours. Paclitaxel followed by cyclophosphamide had greater hematologic toxicity than the opposite schedule or concurrent administration. Pharmacokinetic factors do not seem to account for this sequence-dependent toxicity. As expected, dose-limiting toxicity in all studies has been hematologic. However, granulocyte colony-stimulating factor has ameliorated myelosuppression and allowed considerable dose escalation of cyclophosphamide. This combination has demonstrated activity in previously treated patients with metastatic breast cancer, including the anthracycline-refractory subpopulation that will be reviewed.

Antineoplastic Agents↗

PubMed1996

[Interstitial pneumonia treated with intermittent cyclophosphamide pulse therapy].

A 52-year-old woman was admitted to the hospital because of polyarthralgia and dry coughing. A chest X-ray film showed bilateral diffuse reticulo-nodular shadows. A specimen obtained by transbronchial lung biopsy revealed alveolar septal thickening and infiltration by mononuclear cells. Interstitial pneumonia associated with rheumatoid arthritis was diagnosed. Interstitial pneumonia relapsed soon after the first pulse of corticosteroid therapy. Cyclophosphamide pulse therapy was given in addition to a second pulse of corticosteroid therapy; 700 mg of cyclophosphamide (500 mg/m2) was administered intravenously every month and the dose of steroids was gradually reduced. Cyclophosphamide pulse therapy was repeated three times and the dose of oral corticosteroids was reduced from 60 mg to 35 mg. There was no bone marrow suppression or hemorrhagic cystitis after the cyclophosphamide pulses. Eventually, corticosteroid therapy was stopped with no clinical deterioration. This case suggests that intermittent cyclophosphamide pulse therapy can be effective for treatment of interstitial pneumonia unresponsive to corticosteroids.

Arthritis, Rheumatoid↗

PubMedDate not supplied

Captopril augments antitumor activity of cyclophosphamide in mice.

Patients suffering from cancer (responsive to chemotherapy) are usually treated with a combination of anticancer drugs. In our previous studies, we found that captopril exerted antitumor action on Lewis lung carcinoma (LLC) in mice. This prompted us to evaluate the antitumor effect of captopril combined with cyclophosphamide. BD1F1 mice with LLC received two injections of captopril (5 mg/mouse) at a 1 h interval. Two hours later they were injected with cyclophosphamide (6 mg/mouse). Captopril pretreatment augmented the antitumor action of cyclophosphamide expressed as the survival time and the number of cured mice. Captopril given for five days before cyclophosphamide treatment did not change the antitumor activity of cyclophosphamide.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines.

The anticancer oxazaphosphorine prodrugs cyclophosphamide and ifosfamide are activated in human liver by a 4-hydroxylation reaction catalyzed by multiple cytochrome P450 (CYP) enzymes. In the present study, we used a cultured human hepatocyte model to identify possible inducers of the CYP-catalyzed activation of these two anticancer prodrugs. Treatment of primary cultures of human hepatocytes with phenobarbital, dexamethasone, or rifampin elevated hepatocyte microsomal oxazaphosphorine 4-hydroxylation by up to 200-400% of control for both drug substrates. These inductions were associated with corresponding increases in immunoreactive CYP2B6, CYP2C8, CYP2C9, and CYP3A4, all previously shown to catalyze oxazaphosphorine activation. Rifampin (1 microM, 96-h exposure) was a particularly potent inducer of ifosfamide and cyclophosphamide 4-hydroxylation, as well as of CYP3A protein levels and CYP3A-dependent testosterone 6beta-hydroxylation. CYP3A4, CYP2C8, and CYP2C9 protein levels were also increased by exposure of the hepatocytes to cyclophosphamide or ifosfamide (50 microM), which thereby enhanced their own rates of 4-hydroxylation in the cultured hepatocytes. In one human hepatocyte culture that contained the polymorphically expressed CYP3A5 in addition to the more widely expressed CYP3A4, only CYP3A4 was induced by cyclophosphamide, ifosfamide, and rifampin. These studies: (a) demonstrate an underlying metabolic basis for the clinically important oxazaphosphorine autoinduction pharmacokinetics seen with these drugs in cancer patients; and (b) identify rifampin and other CYP inducers as potentially useful for increasing the rates of cyclophosphamide 4-hydroxylation and ifosfamide 4-hydroxylation in human liver in a manner that could favorably impact the clinical pharmacokinetics of these anticancer prodrugs.

Adult↗

PubMedDate not supplied

In vivo effects of cyclophosphamide on oncogene and suppressor gene expression in a "follow up" study.

Cyclophosphamide is a chemotherapeutical drug, with proved carcinogenic side effects. Our previous experiments showed its effect on the expression of certain oncogenes and tumor suppressor genes. In order to further explore the effects of cyclophosphamide at the gene level an in vivo mouse model was developed. We compared the effects of cyclophosphamide with that of cyclosporine, which is a non genotoxic human carcinogenic chemical. After different time periods of intraperitoneal cyclophosphamide or cyclosporine injection, RNA was isolated from whole organs of experimental animals, and expression of onco/suppressor genes was determined by slot blot hybridisation. In our model we have proved that gene expression changes caused by cyclophosphamide can be detected even six months after treatment without tumor development. Our results support the hypothesis that gene expression investigations could be useful biomarkers in monitoring the effects of environmental carcinogenic compounds.

Animals↗

PubMed1997

Cyclophosphamide induced water intoxication in a woman with Sjögren's syndrome.

Water intoxication is a well described complication of high dose intravenous (i.v.) cyclophosphamide therapy combined with forced hydration. Less well known is that water intoxication can develop even after low dose iv cyclophosphamide. To draw attention to this potentially life threatening complication, we describe a woman who developed acute water intoxication after treatment with low dose iv cyclophosphamide for a sensory neuropathy secondary to Sjögren's syndrome. Rheumatologists should be aware of this serious adverse effect of iv cyclophosphamide because this drug is being used increasingly for treatment of a variety of rheumatological diseases. The pathogenesis, clinical characteristics, treatment, and methods for prevention of cyclophosphamide induced water intoxication are discussed.

Antirheumatic Agents↗

PubMed1998

Reduced gonadal toxicity after i.v. cyclophosphamide administration in patients with nonmalignant diseases.

BACKGROUND: Cyclophosphamide has been used increasingly to treat patients with nonmalignant diseases like primary glomerulonephritis and systemic vasculitis. Thus long-term side effects like gonadal toxicity have become an important issue. Monthly i.v. cyclophosphamide pulse administration leads to a reduction in total dose of 60% compared to daily oral treatment which would be favorable for i.v. therapy. However, the risk of increased germinal damage due to higher peak levels had to be excluded. METHODS: Gonadal toxicity after different modes of cyclophosphamide administration was investigated in men with vasculitis or minimal change glomerulonephritis by measurement of FSH (follicle-stimulating hormone) plasma levels, as well as in Lewis rats by the investigation of testis histology and number of foetuses after mating with healthy female rats. RESULTS: FSH plasma levels after 3 months of treatment were significantly higher in men receiving daily oral cyclophosphamide (28.7 +/- 34 IU/l) compared to i.v. pulse administration (9.5 +/- 5.1 IU/l; p < 0.01) indicating a higher gonadal toxicity after oral treatment. In Lewis rats daily oral gavage led to a significantly reduced number of foetuses and changes in testis histology compared to pulse administration. CONCLUSION: As pulse administration of cyclophosphamide led to a significantly reduced gonadal toxicity compared to oral treatment this administration should be preferred, provided that an equal disease control and relapse rate is achieved.

Administration, Oral↗

PubMedDate not supplied

Augmentation of IL-2 activated natural killer cell adoptive immunotherapy with cyclophosphamide.

UNLABELLED: We have previously documented that adoptively transferred, IL-2 activated natural killer (A-NK) cells can accumulate within established pulmonary metastases. Since we have observed that increases in the accumulation of A-NK cells do not always lead to increases in therapeutic efficacy, we examined the ability of cyclophosphamide to enhance the therapeutic efficacy of A-NK cells. Animals with established B16 melanoma or Lewis lung carcinoma pulmonary metastases were treated with A-NK cell adoptive immunotherapy, either alone or following treatment with chemotherapeutic doses of cyclophosphamide. Adoptive immunotherapy studies with A-NK cells yielded at most a 30% reduction in the number of pulmonary metastases; however, cyclophosphamide (300 mg/kg) consistently reduced the size of metastatic colonies. In contrast, the combination therapy of A-NK cells plus cyclophosphamide was more effective than adoptive immunotherapy alone. In addition, polyethylene glycol IL-2 is superior to IL-2 in these studies. CONCLUSIONS: Our studies suggest that chemoimmunotherapy with A-NK cells plus cyclophosphamide may be more effective than adoptive immunotherapy alone since it results in the reduction in both the size and number of pulmonary metastases.

Adoptive Transfer↗

PubMed1998

[SLE with interstitial pneumonia during cyclophosphamide pulse therapy].

A 49 year-old man was admitted for edema and renal impairment due to SLE. Since he did not improve with predonisolone and methylprednisolone pulse therapy, cyclophosphamide pulse therapy (300 mg div.) was administered. The patient subsequently developed a fever, dyspnea and cough, and interstitial regions of the lungs exhibited shadows on X-ray and CT. The patient also suffered hypoxemia and poor lung function. Since several culture tests and viral antibody tests were negative for infection, antibiotics were not effective, and TBLB indicated interstitial pneumonia, which we speculated was induced by cyclophosphamide. However, this was such a severe case of interstitial pneumonia that it could not be cured merely by discontinuing the cyclophosphamide, but it did improve immediately after starting methylprednisolone pulse therapy. The incidence of cyclophosphamide-induced interstitial pneumonia is very low, but the mortality rate is high. Since cyclophosphamide pulse therapy is often used to treat SLE, attention should be focused on the incidence of interstitial pneumonia.

Cyclophosphamide↗

PubMed1998

Moderate dose escalation for advanced stage Hodgkin's disease using the bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone scheme and adjuvant radiotherapy: a study of the German Hodgkin's Lymphoma Study Group.

The BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, a rearranged and accelerated version of the standard COPP/adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy, has been shown to be effective and safe in a previous pilot study for advanced stage Hodgkin's disease (HD). The present study aimed to determine a maximum practicable dose of three drugs, ie, etoposide, adriamycin, and cyclophosphamide, for which acute toxicities were acceptable and to assess the feasibility of the escalated scheme. Sixty untreated patients with advanced stage HD were enrolled in this study. Radiotherapy was given in 44 patients (73%) after chemotherapy to initial bulk lesions and residual disease. Granulocyte-colony stimulating factor (G-CSF) was given from day 8 to prevent prolonged neutrocytopenia and severe infections. The intended doses of adriamycin, etoposide, and cyclophosphamide in the BEACOPP schedule could be substantially escalated: adriamycin from 25 to 35, cyclophosphamide from 650 to 1,200, and etoposide from 100 to 200 mg/m2. The major toxicities were leukocytopenia and thrombocytopenia with considerable heterogeneity between individual patients. Of 60 patients, 56 (93%) achieved a complete remission (CR). At a median observation of 32 months, the rates of survival and freedom from treatment failure (FFTF) were estimated to be 91% (95% confidence interval 83% to 99%) and 90% (82% to 98%). These results show that a moderate dose escalation of adriamycin, cyclophosphamide, and etoposide of the baseline BEACOPP regimen is feasible. The escalated BEACOPP regimen shows very encouraging results in advanced stage HD and is now being compared in a randomized phase III study with BEACOPP at baseline dose level.

Adolescent↗

PubMed1999

Cyclophosphamide cystitis in mice: behavioural characterisation and correlation with bladder inflammation.

The generation of transgenic 'knock-out' mice which lack genes relevant to pain is becoming increasing common. However, only one visceral pain model, the writhing test, is available in mice. The aim of this study was to adapt cyclophosphamide cystitis, a model of inflammatory visceral pain described in rats, for use in mice, and to characterise its behavioural effects. The toxic metabolites of systemically-administered cyclophosphamide are excreted in the urine, and induce bladder inflammation. We compared the effects of cyclophosphamide (100 and 300 mg/kg i.p., 4 h survival period) and vehicle (saline) in male mice on spontaneous behaviour (4 h continuous video-tape, and a 5-min Open Field test after 4 h). Involvement of the urinary bladder and other abdominal tissues was assessed by macroscopic examination and measurement of Evan's Blue plasma extravasation. Cyclophosphamide (300 mg/kg) produced significant changes in behaviour, including 22 +/- 6 min of 'crises' of visceral pain-related behaviour and a 53% reduction in activity, and also induced haemorrhage and substantial plasma extravasation in the bladder, but no change in other abdominal tissues. We conclude that cyclophosphamide cystitis has many advantages as a model of sub-acute, inflammatory visceral pain in mice. It does not require surgery or intubation, and we have found it to produce consistent, reproducible and quantifiable behavioural changes, which are significantly correlated with the degree of bladder inflammation in the absence of inflammation of other abdominal tissues. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

PubMed2003

Outcome of chilean patients with lupus nephritis and response to intravenous cyclophosphamide.

Several recent open studies suggest that the response rates of lupus nephritis to intravenous (IV) cyclophosphamide are lower than those observed in clinical trials. One explanation could be ethnic differences; for example, black patients more frequently have treatment-resistant lupus nephritis. Another could be the inclusion of patients who are noncompliant with therapy. From our register of 268 systemic lupus erythematosus (SLE) patients examined between 1973 and 1996, 61 patients were treated for proliferative lupus nephritis (17 had World Health Organization [WHO] type III and 43 had WHO type IV) and were followed through to 2001. Exclusion criteria included a serum creatinine level >3 mg/dL. In this retrospective study, we assessed renal outcome and survival with an endpoint of end-stage renal disease (ESRD) or death (Kaplan-Meier). In the univariate analysis, worse prognostic factors for survival were serum creatinine >1.3 mg/dL (p < 0.001), age <30 years (p < 0.001), class 2 renal function stage (p < 0.03), and renal biopsy activity index >7 (p < 0.02). In the subgroup of 26 patients treated with IV cyclophosphamide, survival at 5 and 10 years was 82% and 73%, respectively. The dosage of IV cyclophosphamide was slightly lower than usual and used for a shorter period (median = 23 months) than what is usually recommended because of the high frequency of complications. Renal outcome of the IV cyclophosphamide-treated patients was poorer than that reported in the National Institutes of Health series (ESRD: 15% versus 3%). This low survival rate could reflect the short course and lower doses of IV cyclophosphamide used or ethnic differences. These data emphasize the need for continuous research for better-tolerated drug schemes for treatment of our lupus nephritis patients.

Journal Article↗

PubMed1999

Pulse intravenous cyclophosphamide therapy in pemphigus.

BACKGROUND: Adjuvant therapy is commonly used in pemphigus to mitigate the high morbidity and mortality associated with the use of corticosteroids and improve disease control. However, these adjuvant agents are not without adverse effects of their own, including an increased risk of malignancy with the use of oral immunosuppressives. Intravenous pulse cyclophosphamide, which may be more efficacious and less toxic than oral immunosuppressives, has been used successfully in the treatment of pemphigus. OBJECTIVE: To review 9 patients with severe or previously recalcitrant pemphigus who were treated with intravenous pulse cyclophosphamide therapy. RESULTS: Six of the 9 patients responded to therapy, with 2 patients achieving remission from skin lesions. Five patients were able to decrease their daily dose of prednisone, and 1 was able to discontinue the use of prednisone completely. Most patients experienced minimal or no adverse effects. CONCLUSIONS: Intravenous pulse cyclophosphamide may be an alternative treatment option in patients with pemphigus recalcitrant to standard therapy. The decreased cumulative dose of cyclophosphamide observed with monthly pulse doses may reduce the incidence of secondary malignancies when compared with continuous oral therapy. Controlled trials are needed to further evaluate the efficacy of this mode of therapy.

Adult↗