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PubMed2001

Cyclophosphamide-induced hemorrhagic cystitis in rats that underwent colocystoplasty: experimental study.

PURPOSE: Cyclophosphamide and its derivatives induce hemorrhagic cystitis. A substantial number of patients receive bladder augmentation or replacements using bowel. If patients who have undergone colocystoplasty need treatment with cyclophosphamide before or after the operation, does hemorrhagic cystitis develop? We evaluated the histological changes produced in the colon wall and bladder related to cyclophosphamide and its derivatives in rats that underwent colocystoplasty. MATERIALS AND METHODS: Sprague-Dawley rats of each sex were grouped according to whether they received a single 200 mg./kg. dose of cyclophosphamide, underwent colocystoplasty, underwent each technique or served as controls. The technique of colocystoplasty was the same in all groups. Results were analyzed according to previously reported criteria, by the gross appearance of the bladder and colon segment used for colocystoplasty, and by histological changes. RESULTS: Two weeks after surgery colocystoplasty had not resulted in secondary changes in the implanted colon segment or original bladder, while there were only nonspecific changes of an inflammatory type in the anastomotic area. After cyclophosphamide administration the animals lost considerable weight and in the bladder area we observed hemorrhagic cystitis that was greater in males than in females, and greater in isolated bladder than when the bladder was sutured to the colon segment. In the colon there was no inflammation or hemorrhage damage of the hemorrhagic cystitis type in the bladder. A total of 12 days after colocystoplasty there were no secondary histological changes except in the anastomotic area. A single 200 mg./kg. dose of cyclophosphamide caused substantial weight loss and hemorrhagic cystitis. Cystitis was quantitatively greater in males than in females and greater in isolated bladder than in bladder anastomosed to the colon. CONCLUSIONS: Administering a single dose of cyclophosphamide did not result in lesions in the colon segment used for colocystoplasty analogous to those of the bladder, such as hemorrhagic cystitis.

Anastomosis, Surgical↗

PubMed1979

Use of cyclophosphamide and enhancing serum to suppress renal allograft rejection in the rat.

Cyclophosphamide was tested for its interaction with passive enhancement in suppressing the rejection of kidney allografts in the (DA x Lewis)F1 to Lewis rat strain. Dose response studies with cyclophosphamide showed that 10 mg/kg/day for 14 days was necessary for complete suppression of rejection and indefinite graft survival. Doses of 5 and 3.5 mg/kg/day had only a marginal effect on graft function and survival, although the lymphocytotoxin response to the graft was completely or very substantially suppressed by these smaller doses. The use of passive enhancement with cyclophosphamide at the 5- and 3.5-mg/kg/day doses resulted in a favourable interaction with improved graft function and survival. Interestingly, passive enhancement in combination with 5 mg/kg/day of cyclophosphamide resulted in indefinite graft survival only if cyclophosphamide was given for 28 days. If cyclophosphamide was given for 14 days, rejection was suppressed only during the period of cyclophosphamide treatment.

Animals↗

PubMed1979

The kinetics of salivary elimination of cyclophosphamide in man.

1 The concentrations of cyclophosphamide in plasma and saliva were determined in seven patients following administration of single doses of cyclophosphamide during chemotherapy for lymphoma. 2 The saliva/plasma ratio was 0.77 +/- 0.24 (s.d.) and showed no time-dependence being rapidly established following intravenous and oral administration. 3 The T 1/2 of cyclophosphamide (8.38 +/- 2.25 h) determined from salivary measurements was not significantly different from that in plasma (8.24 +/- 2.60 h). It was not possible to estimate the apparent volume of distribution or total body clearance utilizing the salivary cyclophosphamide concentration without appropriate correction for the saliva/plasma concentration ratio. 4 The binding to the plasma protein of normal plasma of cyclophosphamide was 13.4 +/- 5.3%. The Scatchard plot for binding to bovine serum albumin indicates only weak binding to non-specific sites. 5 Salivary cyclophosphamide therefore indicates the concentration of the unbound fraction of plasma cyclophosphamide.

Blood Proteins↗

PubMed1991

Mobilization of haemopoietic stem cells by cyclophosphamide into the peripheral blood of patients with haematological malignancies.

Thirty one peripheral blood stem cell mobilizations using cyclophosphamide, followed by leucapheresis, were performed in 25 patients with a variety of haematological malignancies. Cyclophosphamide at doses ranging from 0.25 g/M2/day x 4 days to 4 g/M2 on one day were given. Total doses of cyclophosphamide less than 4 g/M2 failed to induce a significant mobilization of stem cells into the peripheral blood. This compares to cyclophosphamide doses of 4 g/M2 given over one or two days where 70%-75% of patients yielded adequate stem cells for transplantation (greater than 20 x 10(4) CFU-GM/kg). Both the presence of tumour cells in the bone marrow and previous chemotherapy within 12 months of cyclophosphamide infusion significantly diminished the patients stem cell mobilizations. The rate of recovery of the patient's leucocyte count following cyclophosphamide was highly correlated to the peak level of PB CFU-GM and is a good indicator of the total stem cell yield. Fever in 50% of patients during the period of cytopaenia was the only complication seen in our patients and thus high dose cyclophosphamide is a suitable and safe agent for mobilizing haemopoietic stem cells.

Adult↗

PubMed1992

A comparison of peripheral blood stem cell mobilisation after chemotherapy with cyclophosphamide as a single agent in doses of 4 g/m2 or 7 g/m2 in patients with advanced cancer.

We used cyclophosphamide at a dose of 7 g/m2 in patients with advanced cancer and compared the efficacy of this treatment to generate peripheral blood stem cells (PBSC) with the previously reported regimen of cyclophosphamide 4 g/m2 in a similar group of patients. None of these patients received haemopoietic growth factors. Twenty-two patients received 7 g/m2 and 37 received 4 g/m2. PBSC were collected by apheresis after the leukocyte count recovered to 1.0 x 10(9)/L. The yield of colony forming unit-granulocyte macrophage (CFU-GM) was higher for the 7 g/m2 group with a median of 35 x 10(4)/kg versus 15 x 10(4)/kg body weight (BW) (p < 0.05) and higher mononuclear cell yield with medians of 4.2 x 10(8)/kg compared with 3.1 x 10(8)/kg BW (p < 0.001). The percentage of patients achieving the minimum safe level of > 15 x 10(4) CFU-GM/kg BW was higher in the 7 g/m2 cyclophosphamide group (82%) than the 4 g/m2 cyclophosphamide group (51%). The duration of significant neutropaenia was a median of 11 compared with nine days (p < 0.004) and all patients receiving 7 g/m2 required admission to hospital and intravenous antibiotic therapy compared with 44% in the 4 g/m2 group. There was one death during the period of neutropaenia after cyclophosphamide in each group. Nineteen per cent of patients required platelet transfusions after cyclophosphamide 7 g/m2 compared with 18% after 4 g/m2. We conclude that the 7 g/m2 cyclophosphamide gives a higher yield of haemopoietic progenitor cells than the 4 g/m2 but at increased clinical toxicity.

Academies and Institutes↗

PubMed2006

L6-S1 spinal nerve stimulation reduces micturition frequency in anaesthetized rats with cyclophosphamide-induced cystitis.

OBJECTIVE: To further investigate the rationale for using spinal nerve stimulation (SNS) for treating bladder overactivity associated with cystitis in a rat model of cyclophosphamide-induced cystitis, as several studies suggested that symptoms associated with chronic cystitis could be treated using stimulation of sacral spinal nerves, but the mechanisms by which it works are unknown. MATERIALS AND METHODS: Cystitis was induced by i.p. injection of cyclophosphamide 48 h before the experiments in anaesthetized male rats. Neurograms were taken by placing a recording electrode onto the pelvic nerve and a stimulating electrode on either the L6 or S1 ipsilateral spinal nerves. Two selected intensities were then evaluated for SNS in control and cyclophosphamide-treated rats during cystometry. RESULTS: Cyclophosphamide resulted in significant bladder overactivity. There was no apparent difference in the neurograms generated in response to SNS of the S1 and L6 spinal nerves, and between cyclophosphamide and control rats. Intensities of 200 microA (Adelta-fibre-specific) and 2 mA (Adelta+ C-fibres) were chosen for SNS. Continuous SNS at 200 microA significantly reduced the frequency of voiding and non-voiding contractions in cyclophosphamide-treated rats. SNS at 2 mA resulted in the abolition of voiding contractions, accompanied by continuous leakage of urine. CONCLUSION: SNS recruiting only Adelta-fibre produced fewer voiding contractions in cyclophosphamide-treated rats, to a level similar to that from the control rats. These results support the ability of SNS to decrease bladder overactivity in a pathophysiological model of chemical irritation of the bladder.

Animals↗

PubMedDate not supplied

Pharmacokinetics of cyclophosphamide (CP) and 4-OH-CP/aldophosphamide in systemic vasculitis.

Cyclophosphamide given in association with corticosteroids has markedly improved the prognosis of systemic vasculitis. Little information has been reported on cyclophosphamide pharmacokinetics in these diseases and data evaluating its metabolite, 4-hydroxycyclophosphamide/aldophosphamide, pharmacokinetics and concentrations are lacking. Cyclophosphamide was administered as a 1-h intravenous infusion every 3 weeks for six cycles to ten vasculitis patients. Serum cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide concentrations were assayed on the first cycle of the treatment by reversed-phase high-pressure liquid chromatography with ultraviolet detection. The mean (+/- SD) 4-hydroxycyclophosphamide/aldophosphamide and cyclophosphamide areas under the serum concentration-time curves were, respectively, 1.86 +/- 1.12 and 154.1 +/- 62.7 mg/L x h with a ratio of 1.30 +/- 0.76%. The mean maximum serum 4-hydroxycyclophosphamide/aldophosphamide was reached 2.3 h after cyclophosphamide administration. The mean (+/- SD) cyclophosphamide and 4-hydroxycyclophosphamide/aldophosphamide half-lives were, respectively, 5.5 +/- 3.1 and 7.6 +/- 2.3 h. The results are consistent with those obtained for cancer patients, in spite of a wide interpatient variability of concentrations and pharmacokinetic parameters.

Adult↗

PubMed1996

The effects of cyclophosphamide on the pharmacokinetics of triiodothyronine in the male rat.

In the present study, the possibility that cyclophosphamide or a cyclophosphamide metabolite may be accelerating the clearance of triiodothyronine has been examined. Following administration of exogenous triiodothyronine to saline- and cyclophosphamide-treated rats, the area under the plasma concentration time curve (AUC), apparent clearance (CLapp) and half-life of triiodothyronine were measured. AUC (34.43 +/- 12.34 compared with 33.32 +/- 9.92 nmol h L-1). CLapp (36.30 +/- 12.89 compared with 37.51 +/- 11.16 mL h-1) and half-life (7.50 +/- 1.39 compared with 6.40 +/- 0.96 h) were not significantly different in the control rats compared with the cyclophosphamide-treated rats. As cyclophosphamide does not appear to alter the elimination of triiodothyronine, it is likely that cyclophosphamide or a cyclophosphamide metabolite is acting at the hypothalamo-pituitary axis, reducing the synthesis or release of thyroid stimulating hormone and consequently decreasing the levels of triiodothyronine and thyroxine.

Alkylating Agents↗

PubMed1977

Effect of cyclophosphamide in vitro and on vaccinia virus replication in tissue culture.

The effect of cyclophosphamide on the growth of Vero, BSC-1, and HeLa cells in monolayer cultures was studied. By using hemocytometer counts and tritiated thymidine uptake as indicators of growth, it was found that cyclophosphamide significantly interfered with the metabolism of Vero and BSC-1 cells when sustained in Leibovitz medium. Vero cells and HeLa cells grown in Eagle medium were not affected by exposure to cyclophosphamide. Vaccinia virus replication in Vero cell monolayer cultures incubated with cyclophosphamide was markedly augmented, and this enhanced growth was reflected by virus quantitation techniques and metabolic studies using tritiated thymidine uptake. No difference in the distribution of infectious particles was found when cyclophosphamide-treated and control infected cultures were compared. Pathways other than through hepatic enzymes appear available to activate cyclophosphamide in vitro. These effects are dependent on both the cell type and the medium in which the cells are grown. Cyclophosphamide can facilitate vaccinia virus replication in vitro through metabolic interactions at the cellular level. The precise mechanisms underlying this effect require further study.

Cell Line↗

PubMed1996

Incidence of ovarian failure in systemic lupus erythematosus after treatment with pulse cyclophosphamide.

OBJECTIVE: To investigate the incidence of ovarian failure after pulse cyclophosphamide treatment in systemic lupus erythematosus (SLE) and to compare this with two control groups: SLE patients treated with azathioprine, and a healthy age matched population. METHODS: All women patients with SLE treated with pulse cyclophosphamide in our department were identified and questioned concerning menstrual history. All the hospital notes were reviewed and details recorded on dose of cyclophosphamide, duration of treatment, side effects and lowest pretreatment neutrophil and leucocyte counts during the course of treatment. Disease controls were recruited from our department and healthy controls from the local family health services authority (FHSA) register. RESULTS: Incidence of ovarian failure in the premenopausal cyclophosphamide treated group was 54% and the incidence of premature menopause (occurring before age 40 years) was 41%. Increasing age at start of treatment showed a linear trend with incidence of ovarian failure (p = 0.01). Using logistic regression, increasing duration of treatment was related to incidence of ovarian failure (p = 0.047 in those treated age 35 years or younger). An association between the lowest neutrophil count throughout the treatment period, when taken immediately before each planned cyclophosphamide pulse, and the incidence of ovarian failure was also demonstrated (p = 0.04 in those treated before age 40 years). CONCLUSION: Ovarian failure--in particular, premature failure after treatment with pulse cyclophosphamide--is common. Factors associated with increased risk include greater age at start of treatment, longer period of treatment, and greater degree of marrow suppression as assessed by the neutrophil count immediately before each planned cyclophosphamide pulse.

Adolescent↗

PubMed1987

Studies on the mechanism of action of diallyl sulfide, an inhibitor of the genotoxic effects of cyclophosphamide.

Diallyl sulfide, a component of garlic oil, has been previously shown to inhibit induction of nuclear aberrations in the colons of mice treated with 1,2-dimethylhydrazine, a colon carcinogen. The ability of this agent to block cyclophosphamide-induced nuclear aberrations in urinary bladder and hair follicles was tested. [14C]Cyclophosphamide was injected and urine was collected to determine the disposition of metabolites of cyclophosphamide in mice treated with diallyl sulfide. This agent was capable of blocking nuclear aberration induction by cyclophosphamide in bladder and hair follicles. The effect was not mediated through inhibition of mitosis as determined by [3H]thymidine autoradiography in hair follicles. Diallyl sulfide pretreatment decreased the amount of radioactivity excreted in the urine in the first 24 h following cyclophosphamide treatment and blocked the appearance of acrolein, a cytotoxic metabolite of cyclophosphamide, in the urine over this time period. These results suggest that diallyl sulfide acts by conjugating the toxic metabolites of cyclophosphamide, thereby limiting their systemic circulation and diverting their route of excretion from the urine.

Allyl Compounds↗

PubMed1989

Modulation of endoperoxide product levels and cyclophosphamide-induced injury by glutathione repletion.

Glutathione is a tripeptide important in a number of diverse cellular functions including enzymatic reactions involved in prostaglandin endoperoxide metabolism. We have previously reported that cyclophosphamide administration to rats results in acute lung injury manifested by increased bronchoalveolar lavage albumin concentrations. In the current study we examine whether cyclophosphamide treatment affects pulmonary glutathione stores or bronchoalveolar endoperoxide metabolic product levels and whether these effects may be related to acute lung injury caused by the drug. We show that cyclophosphamide treatment causes a dose-dependent reduction in pulmonary glutathione stores 4 h after drug administration. In addition, acute lung injury as the result of cyclophosphamide can be abrogated by coadministration of oxothiazolidine carboxylate, an intracellular cysteine delivery system that also reverses pulmonary glutathione depletion induced by cyclophosphamide in our study. Finally, cyclophosphamide treatment reduces prostaglandin E2 concentrations in bronchoalveolar lavage and alveolar macrophage culture supernatant in a dose-dependent fashion and increases bronchoalveolar thromboxane concentrations in low dose-treated animals. These effects are reversed to a variable degree by coadministration of oxothiazolidine carboxylate. Our study suggests in vivo pulmonary arachidonic acid metabolism and cyclophosphamide-induced acute lung injury are modulated by cellular glutathione stores. These findings may have important implications for the treatment of acute lung injury.

Animals↗

PubMed2005

Dose-dense sequential adriamycin-Paclitaxel-cyclophosphamide chemotherapy is well tolerated and safe in high-risk early breast cancer.

OBJECTIVE: The feasibility of dose-dense sequential adjuvant chemotherapy with Adriamycin, paclitaxel and cyclophosphamide was evaluated. METHODS: Fifty-five high-risk breast cancer patients were enrolled. The following chemotherapy schedule was used: 4 x Adriamycin --> 4 x paclitaxel --> 4 x cyclophosphamide, q 2 weeks (Adriamycin, 60 mg/m2; paclitaxel, 200 mg/m2 over 3 h, and cyclophosphamide, 800 mg/m2). RESULTS: The dose intensity was 95.0, 99.8 and 97.4% of that planned for treatment with Adriamycin, paclitaxel and cyclophosphamide, respectively. During treatment with Adriamycin, paclitaxel and cyclophosphamide, 20, 12.7 and 25.5% of the patients, respectively, did not need filgrastim to maintain the dose density. The average number of filgrastim doses per cycle, when necessary, was 3.6. Neutropenia of grade 3-4 was found in 67.3, 13.5 and 10.0% of the patients after treatment with Adriamycin, paclitaxel and cyclophosphamide, respectively. A single case of febrile neutropenia was observed. Anemia occurred in 96.4% of the patients, and was significantly more frequent (p = 0.031) and more severe (p = 0.002) during paclitaxel treatment than in the other chemotherapy cycles. CONCLUSIONS: Dose-dense sequential chemotherapy with Adriamycin, paclitaxel and cyclophosphamide is well tolerated and safe. Individual treatment with granulocyte colony-stimulating factor is needed to maintain the dose density in most patients, but some tolerate this regimen without it, probably due to differences in drug clearances.

Adult↗

PubMed2002

Intravenous pulse administration of cyclophosphamide is an effective and safe treatment for sensitized cardiac allograft recipients.

BACKGROUND: The proportion of cardiac transplant recipients with preexisting sensitization to HLA alloantigens has been increasing. Sensitization prolongs duration to obtaining a donor and predicts poorer long-term allograft survival because of increased risk of cellular rejections. We investigated the effect of cyclophosphamide pulse therapy in sensitized cardiac allograft recipients. METHODS AND RESULTS: Pretransplant and posttransplant outcomes were compared between 88 cardiac allograft recipients at risk for sensitization and 26 sensitized recipients treated with intravenous cyclophosphamide pulse therapy together with intravenous immune globulin before transplant and as part of a cyclosporine-based triple immunosuppressive regimen after transplant. Preformed IgG anti-HLA antibodies predicted longer duration to transplantation, earlier cellular rejection, and 2.7-fold higher cumulative rejection frequency (P=0.002). Before transplant, cyclophosphamide reduced waiting time and mortality to levels in nonsensitized patients. After transplant, cyclophosphamide prevented induction of IgG anti-HLA class II antibodies and interleukin-2 receptor--positive T-cell outgrowth from biopsy sites (both P<0.01), prolonged the rejection-free interval (P=0.009), and reduced cumulative rejections to levels in nonsensitized patients (P=0.003). By multivariable analysis, the risk of rejection was 3.7-fold higher in patients treated with mycophenolate mofetil than patients treated with cyclophosphamide (P=0.019). There were no differences in infectious or other significant complications. CONCLUSIONS: Immunosuppression incorporating intravenous cyclophosphamide before and after transplantation is safe and highly effective in sensitized cardiac transplant recipients. When used after transplantation as part of triple immunosuppression, cyclophosphamide is superior to mycophenolate mofetil in reducing rejection. The mechanism may involve prevention of diversification of the recipient immune response to donor HLA class II molecules.

Adult↗

PubMed1996

Lung toxicity associated with cyclophosphamide use. Two distinct patterns.

Cyclophosphamide-induced lung toxicity may be difficult to recognize because of the presence of confounding variables such as concomitant use of other cytotoxic drugs, opportunistic infections, diffuse pulmonary malignancy, radiation pneumonitis, and oxygen toxicity. The purpose of this retrospective analysis was to identify the clinical spectrum of pulmonary toxicity of cyclophosphamide. In our review of case records, we sought to identify patients in whom cyclophosphamide was the only identifiable etiologic factor for lung toxicity. In a 20-yr period six patients were identified with cyclophosphamide-induced lung disease, including five men and one woman ranging in age from 42 to 78 yr. Clinical features of toxicity include dyspnea, fever, cough, new parenchymal infiltrates, gas exchange abnormalities on pulmonary function tests, and pleural thickening on chest roentgenogram. Two patterns of cyclophosphamide-induced lung toxicity were identified. A single patient presented with early-onset pneumonitis and responded to discontinuation of the drug. Five patients with late-onset pneumonitis developed progressive pulmonary fibrosis associated with bilateral pleural thickening. Patients with late-onset pneumonitis showed no response to cessation of cyclophosphamide and institution of corticosteroid therapy. Three of these patients died of respiratory failure. Careful review of the individual cases reported in the literature as cyclophosphamide lung toxicity revealed only 12 cases in whom none of the additional confounding factors could be identified. These could easily be divided in the same two categories. Early-onset pneumonitis is reversible and may respond to corticosteroid therapy. Late-onset pneumonitis, frequently associated with pleural thickening, is clinically distinct from idiopathic pulmonary fibrosis but has a chronically progressive course. It appears unresponsive to corticosteroid therapy.

Adult↗

PubMed1996

Reversal of erythema multiforme major with cyclophosphamide and prednisone.

OBJECTIVE: To report a case of erythema multiforme (EM) major treated with cyclophosphamide and prednisone. SETTING: General medicine and dermatology consult services, Department of Veterans Affairs Medical Center. CASE SUMMARY: A 44-year-old man with C4-C5 quadriplegia developed a skin reaction characterized by a painful, generalized maculopapular rash, bullae, ulceronecrotic lesions, and mucosal and epidermal sloughing after taking trimethoprim/sulfamethoxazole. The patient was treated with intravenous cyclophosphamide 150 mg infused over 1 hour every 24 hours and oral prednisone 15 mg every 6 hours. After two doses of cyclophosphamide, formation of bullae and epidermal sloughing had ceased, and the erythema was markedly diminished. Cyclophosphamide was discontinued before the third dose because of evolving leukopenia. Prednisone therapy was continued until the patient was discharged on hospital day 5, at which time the dosage was tapered. DISCUSSION: Cyclophosphamide has been used extensively for other dermatologic reactions. Relief of pain and regression of the lesions in our patient occurred more quickly than anticipated. CONCLUSIONS: Treatment of EM major with cyclophosphamide combined with prednisone appeared to be highly successful in this patient. Cyclophosphamide may be an effective, empiric initial treatment in reversing EM major.

Adult↗

PubMedDate not supplied

Modified oral ondansetron regimen for cyclophosphamide-induced emesis in lupus nephritis.

OBJECTIVE: To evaluate the antiemetic efficacy of a modified regimen of oral ondansetron and dexamethasone in patients with lupus nephritis undergoing treatment with cyclophosphamide whose conventional antiemetic regimen had failed. DESIGN: A before-after prospective observational pilot project. SETTING: A federal research hospital. PATIENTS: Fourteen outpatients with lupus nephritis receiving intravenous cyclophosphamide 0.75-1.0 g/m2 had previously experienced chemotherapy-induced emetic events (vomiting or retching) while receiving a standard combination intravenous antiemetic regimen. The regimen consisted of four doses of thiethylperazine 10 mg and diphenhydramine 25 mg every 6 hours, and two doses of lorazepam 0.5 mg every 6 hours starting at 1 hour prior to cyclophosphamide. A subset of 8 patients previously completed a blinded study in which they received the intravenous formulation of ondansetron (4 doses of 4-16 mg q4h) administered orally beginning 30 minutes prior to the cyclophosphamide infusion. MAIN OUTCOME MEASURES: The number of emetic events and cost of drug administration were assessed for the modified ondansetron intervention and compared with those of the standard antiemetic regimen. The incidence of emetic events and visual analog nausea scores for the subset of eight patients were also evaluated. INTERVENTIONS: To account for the delayed onset of emesis associated with cyclophosphamide, patients received both ondansetron 8 mg orally every 4 hours (3 doses) and dexamethasone 10 mg orally (1 dose) beginning 4 hours after the cyclophosphamide infusion. This is different from the manufacturer's recommended dose schedule, in which ondansetron is administered prior to chemotherapy. RESULTS: No emetic events were observed following the administration of oral ondansetron/dexamethasone. The 95% confidence interval for the true rate of emesis was 0% to 19.3%. There was a significant difference in efficacy between ondansetron/dexamethasone and the triple antiemetic regimen (p < 0.0002). None of the patients experienced adverse effects while receiving the ondansetron/dexamethasone regimen. Cost comparisons (including admixture and nursing administration times) for standard combination therapy and oral ondansetron/dexamethasone were $109.09 and $70.24, respectively. No difference in emetic events or nausea ratings was observed between oral ondansetron/dexamethasone tablets and oral administration of ondansetron using the intravenous formula. CONCLUSIONS: This study suggests that a modified oral ondansetron/dexamethasone regimen is safe and efficacious, and costs less than alternative regimens to prevent cyclophosphamide-induced emesis in patients with lupus nephritis.

Administration, Oral↗

PubMed2005

Contamination of syringe plungers during the sampling of cyclophosphamide solutions.

The presence of cytotoxic agents in the urine of operators and in their environment has been demonstrated. The pharmacokinetics of the urinary elimination of cyclophosphamide suggests that these drugs are absorbed cutaneously during handling. In the framework of a more general study on the contamination of hospital environment, the present study addresses the possible presence of cytotoxic agents on the plungers of syringes. The report is based on results indicating that the bacterial contamination of a plunger may result in the contamination of the solution being sampled. The study was divided into two phases. The first phase consisted in measuring the contamination of the plungers of eight syringes used for handling cyclophosphamide. Cyclophosphamide was analysed by gas chromatography-mass spectrometry with a detection limit of 0.1 ng/ml. The aim of the second phase was to localize the contamination on the plunger and thus determine the amount of drug that comes into contact with the gloves of the operators. The contamination was quantified by measuring the activity of metastable technetium. The results of the first phase showed that all the plungers were contaminated with cyclophosphamide amounts varying from 3.7 to 445.7 ng. The second phase showed that the infiltration of liquid onto the plunger depended on the solution being sampled. Almost no infiltration was seen with labelled water, but contamination appeared after the first sampling of a cyclophosphamide solution, then increased as a function of the number of times the plunger was pushed in and out. These results indicate that cyclophosphamide solutions infiltrate onto the plungers of syringes. They suggest that the general procedure for handling cytotoxic agents should be modified, and a regular replacement of syringes should be enforced. They also partly explain why the gloves of 50-90% operators are contaminated after a single preparation. The contamination seems to depend on the type of solution sampled and the number of samplings. Initial investigations by the manufacturer of the syringes had shown that the acid pH of cyclophosphamide solutions may affect the lubricant of the joint. Our study demonstrates that the contamination of plungers is one of the sources of environmental contamination for health workers handling antineoplastic agents, even in the absence of manipulation errors. More generally, these results demonstrate that the exposure of operators cannot be clearly described unless all existing sources of contamination in their environment are identified. The implementation of suitable procedures should thus take into account all possible sources of contamination, including technical facilities such as the use of a safety cabinet or an isolator.

Antineoplastic Agents↗