Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CYCLOPHOSPHAMIDE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,315 records · Page 73Linked to original sources
PubMed1990

Large-scale collection of circulating haematopoietic progenitors in cancer patients treated with high-dose cyclophosphamide and recombinant human GM-CSF.

Circulating haematopoietic progenitors from 36 cancer patients were collected by continuous-flow leukapheresis during the phase of rapid haematopoietic recovery after pancytopenia induced by high-dose cyclophosphamide and then cryopreserved for autologous transplantation. 20 of the patients also received intravenous infusion of recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) for 7, 10 or 14 days after cyclophosphamide. 106 leukapheresis procedures were done for 2-5 consecutive days. Leukapheresis was started significantly earlier in patients receiving rhGM-CSF. In these patients, yields of peripheral blood elements (leucocytes, mononuclear cells, haematopoietic progenitors and platelets) were significantly higher than in controls treated with cyclophosphamide only. In particular, the mean number of granulocyte-monocyte colony-forming cells was 43.88 X 10(4) vs. 6.16 X 10(4) per kg patient body weight per leukapheresis. Side-effects of leukapheresis were limited to central venous catheter occlusion and fever in 4% and 2% of all procedures, respectively.

Adult↗
PubMed1984

Effects of vitamin A on cyclophosphamide mutagenicity in vitro (Ames test) and in vivo (mouse micronucleus test).

The effect of vitamin A on cyclophosphamide mutagenicity was measured both in vitro and in vivo. In the Ames test in Salmonella typhimurium TA1535 with mouse-liver S-9 mix, the addition of retinol, retinyl acetate or retinyl palmitate caused a dose-dependent inhibition of cyclophosphamide mutagenicity. In the micronucleus test in male NMRI mice fed low, normal or high levels of vitamin A, the induction of micronuclei in bone marrow by an ip dose of cyclophosphamide was unaffected by vitamin A status. Thus, this study provides no evidence that activation of a procarcinogen in the liver or bone marrow of mice can be modified by vitamin A. One of the possible reasons for the observed absence of inhibition by vitamin A in vivo may be a lack of correlation between the oral dose of retinoid and the resulting level of vitamin A in the bone marrow. The difference between results in vitro and in vivo may also have been due to a difference in the availability and potency of added vitamin A in vitro compared with the forms absorbed and stored in vivo.

Animals↗
PubMed1986

The effect of low dose-rate and cyclophosphamide on the radiation tolerance of the mouse lung.

Mice were given cyclophosphamide 30 mg/kg intraperitoneally before thoracic irradiation at high dose-rate (HDR, 100 cGy/min) or low dose-rate (LDR, 5 cGy/min). The development of pneumonitis was monitored by regular measurement of breathing rate. Peak rises in breathing rate occurred around 4-9 weeks in those given cyclophosphamide before irradiation, and around 14-16 weeks in those given radiation alone, regardless of dose-rate. The dose reduction factor (DRF = LDR/HDR ratio) for LDR irradiation was congruent to 1.8 but LDR sparing was abolished (DRF congruent to 1.0) when cyclophosphamide was given before irradiation.

Animals↗
PubMed1993

Effect of glucose-mediated pH reduction and cyclophosphamide on oxygenation of transplanted rat tumors.

PURPOSE: Glucose-mediated reduction of tumor pH is under investigation as a means to improve the therapeutic index of anticancer agents. An improvement of glucose supply to tumors is, however, likely to influence various metabolic and pathophysiological parameters apart from pH which, in turn, could modulate H+ ion-mediated effects. As a first step to identify changes in these parameter, we have investigated the effect of glucose-mediated pH reduction on oxygenation of malignant tissues either per se or in combination with a pH-sensitive drug, cyclophosphamide. METHODS AND MATERIALS: H+ ion and oxygen-sensitive semi-microelectrodes were used to measure pH and pO2 in transplanted TV1A and AH13r rat tumors at normoglycemia and following high-dose intravenous glucose infusion. RESULTS: In both tumors analyzed, pH reduction was accompanied by a decrease in pO2. In TV1A tumors, for example, the mean (median) pO2 decreased from 8.2 mm Hg (3.7 mm Hg) to 3.9 mm Hg (1.7 mm Hg) at 2 hr and 2.9 mm Hg (1.9 mm Hg) at 24 hr, respectively, after raising the plasma glucose concentration to 25 +/- 2 mmol/l. At the same time points, the mean pH had declined from 6.89 to 6.29 and 6.24, respectively. The class of pO2 readings < 5 mm Hg increased from a pretreatment value of 65% to approximately 90% at 24 hr. In contrast, cyclophosphamide treatment resulted in improved oxygenation of AH13r tumors, an effect first observed at 24 hr after drug administration. When both modalities were combined, cyclophosphamide partly prevented the acidosis-associated decrease in oxygen partial pressure. CONCLUSION: The results of this study indicate that, within the context of the therapeutic approach used, cytotoxic agents should be employed which are more active against hypoxic than against well-oxygenated cells. In particular, glucose-mediated reduction of oxygen partial pressure in malignant tissues may be exploited to increase the fraction of hypoxic cells prior to administration of drugs activated in hypoxic cells by reductive metabolism (bioreductive agents).

Animals↗
PubMed1994

Phase I pharmacokinetic study of the hypoxic cell sensitizer etanidazole with carboplatin and cyclophosphamide in the treatment of advanced ovarian cancer.

PURPOSE: A Phase I study was undertaken to determine the maximum tolerated dose of the hypoxic cell sensitizer etanidazole which could be administered with carboplatin and cyclophosphamide, to determine whether adequate serum levels of etanidazole were achieved to allow for alkylating agent sensitization, and whether pretreatment with etanidazole altered carboplatin pharmacokinetics. METHODS AND MATERIALS: Patients received 2 g/m2 of intravenous etanidazole followed by a second dose of 4 g/m2 90 min later, followed by intravenous carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2) for four treatment cycles. Patients received an additional two cycles of carboplatin and cyclophosphamide without etanidazole. RESULTS: Two patients who received a total of 24 g/m2 of etanidazole developed Grade 1 neurotoxicity, and therefore etanidazole doses were not escalated further. The grade of granulocytopenia was worse after cycles with etanidazole than after those without (p = 0.03), but clinical outcome was not different. Etanidazole levels were adequate for alkylating agent sensitization (> 70 ug/ml) in all patients for the majority of the 7 h of testing. Pharmacokinetic data suggested t1/2 alpha and t1/2 beta for carboplatin were prolonged after pretreatment with etanidazole. CONCLUSION: Etanidazole, 2 g/m2 followed by 4 g/m2 90 min later, is safe and results in adequate serum levels for alkylating agent sensitization. Neurotoxicity appears to prevent dose escalation of etanidazole, and an interaction between etanidazole and carboplatin may have enhanced neurotoxicity in these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Colorimetric determination of cyclophosphamide and ifosphamide.

A simple colorimetric method for the determination of cyclophosphamide and ifosphamide in pure and in dosage forms is suggested. It depends on the reaction of the secondary amino group in both, with nitrous acid, thus forming a nitroso derivative which can be measured at 325 nm for cyclophosphamide and 335 nm for ifosphamide. Beer's law is obeyed with concentrations from 20 to 90 micrograms ml-1 for cyclophosphamide and from 5 to 100 micrograms ml-1 for ifosphadmie, with repeatability of 99.83 +/- 0.256% and 99.72 +/- 0.649%, respectively. Application to different pharmaceutical preparations has shown no significant difference when compared with the B.P. 1988 method.

Chemistry, Pharmaceutical↗
PubMed2006

Potentiation of the activity of cisplatin and cyclophosphamide by trimidox, a novel ribonucleotide reductase inhibitor, in leukemia-bearing mice.

We describe the use of the new ribonucleotide reductase inhibitor, trimidox (TDX), in combination chemotherapy under in vitro and in vivo conditions with cisplatin and cyclophosphamide. In vitro, the combination of TDX and cisplatin was tested in L1210 cells. The combination caused concentration dependent antagonistic or additive effects. However, the combination of TDX-cisplatin-cyclophosphamide in vivo is highly synergistic in both, the L1210 and P388D1 leukemia mouse models. Both combinations, TDX with cisplatin or TDX with cyclophosphamide were also synergistic in the L1210 and P388D1 leukemia animal models.

Animals↗
PubMed2004

Monitoring of urinary acrolein concentration in patients receiving cyclophosphamide and ifosphamide.

Acrolein, the metabolite of cyclophosphamide and ifosphamide, irritates mucous membranes and is considered pathogenetically important in hemorrhagic cystitis. Increasing fluid intake or administering sodium 2-mercaptoethanesulfonate (mesna), a thiol compound, can reduce the risk of this complication. We measured urinary acrolein concentrations using headspace-solid-phase microextraction gas chromatography and mass spectrometry (headspace-SPME-GC-MS) in 19 patients receiving cyclophosphamide and ifosphamide (36 occasions). Peak acrolein concentrations occurred at 1-12h (mean +/- S.D., 5.0+/-2.7) after starting therapy, ranging from 0.3 to 406.8 nM (39.7+/-76.7), with varying patterns over time. Maintaining high urine volume was important for preventing increases in urinary acrolein concentration, as urinary acrolein concentration tended to rise as urine volume decreased. Urinalysis detected occult blood in three cases, but the patients had no clinical symptoms of hemorrhagic cystitis. In clinical trials involving cyclophosphamide and ifosphamide, monitoring of urinary acrolein concentration could indicate when to take heightened preventive measures against hemorrhagic cystitis.

Acrolein↗
PubMed2004

The argument against the use of cyclophosphamide and mitoxantrone in the treatment of multiple sclerosis.

Mitoxantrone (MITX) and cyclophosphamide (CPM) are potent immunosuppressive agents with efficacy in the treatment of multiple sclerosis (MS). Both agents appear effective in those patients with active inflammatory disease but are probably less effective in patients with a secondary progressive (SP) course dominated by a degenerative component. Given these agents are effective patients with active inflammation the question arises as to whether they are more effective than high dose interferon therapy. Interferon beta administered at high dose and high frequency suppresses enhancing lesions by as much as 90% and brings about a 35% decrease in relapse rates in addition to decreasing the progression of disability. Interferons have an excellent safety profile even after years of administration. What then is the advantage of immunosuppressive agents such as cyclophosphamide and mitoxantrone over safer and still effective treatments? The answer lies in the magnitude of effect in those with the most active and aggressive disease states. While interferons are safe and effective in those with mild or moderate inflammatory disease states, they are probably not sufficient to bring about control in disease that is highly active and resilient. Both mitoxantrone and cyclophosphamide have the ability to suppress inflammation that may be resistant to therapy with more conservative agents. Given the safety profile of these agents their use should be restricted to those patients with aggressive disease resistant to treatment with more conservative agents.

Cyclophosphamide↗
PubMed2006

Phase II study of pegylated liposomal doxorubicin HCl (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small cell lung cancer.

BACKGROUND: Despite chemotherapy and radiotherapy for small cell lung cancer (SCLC), most patients die within 2 years. Response rates for second-line chemotherapy are 15-25%, with a median survival of 5 months. Caelyx, a pegylated liposomal formulation of doxorubicin, may be better tolerated and has activity in SCLC. PATIENTS AND METHODS: Thirty-two patients were enrolled in a phase II study of intravenous Caelyx (35 mg/m2), cyclophosphamide (750 mg/m2) and vincristine (1.2 mg/m2) every 21 days as second-line therapy in SCLC for up to six cycles. RESULTS: Thirty patients were evaluable for response, with a response rate of 10%. Another two had an unconfirmed response. Stable disease (SD) for >or=2 cycles was seen in an additional 53%. Grade 3 or 4 non-hematologic toxicity was seen in 17 (55%) patients (26 [22%] cycles) and included fatigue, mucositis, plantar-palmar erythrodysesthesia, rash and neuropathy. Twelve patients required transfusions. All patients on study have now expired, with a median survival of 28 weeks (7 months). For patients with SD or partial response, median time to progression was 15 weeks. CONCLUSION: The combination of Caelyx, cyclophosphamide and vincristine, despite cyclophosphamide and Caelyx dose reductions, has modest activity in relapsed SCLC with acceptable toxicity.

Adult↗
PubMed2004

Pulse IV cyclophosphamide in ocular inflammatory disease: efficacy and short-term safety.

PURPOSE: To assess the efficacy and short-term safety of appropriately monitored pulse IV cyclophosphamide therapy in the treatment of patients with severe or treatment-resistant autoimmune ocular inflammatory disease. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Thirty-eight patients with severe or recalcitrant ocular inflammation of diverse etiologies. METHODS: Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Thirty-eight consecutive patients treated with pulse IV cyclophosphamide between January 1995 and March 2002 were analyzed. MAIN OUTCOME MEASURES: The control of inflammation, steroid-sparing effect, visual acuity, and adverse reactions. RESULTS: A positive response to treatment occurred in 68% of patients during the study period, with 55% achieving complete quiescence. A steroid-sparing effect was achieved in all patients previously on systemic steroid, allowing successful discontinuation of the drug in 41%. Visual acuity was maintained in 66% and improved in 21% of involved eyes. The most common side effects observed were fatigue (63%), nausea (32%), and headache (22%). None required a permanent discontinuation of therapy. CONCLUSIONS: Pulse IV cyclophosphamide is an effective therapeutic modality in patients with severe or treatment-resistant ocular inflammatory disease.

Adolescent↗
PubMed1999

Cyclophosphamide pulse therapy in optic neuritis due to systemic lupus erythematosus: an open trial.

OBJECTIVE: To evaluate the efficacy of intravenous cyclophosphamide pulse therapy in patients with optic neuritis associated with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Ten consecutive patients with optic neuritis due to SLE whose condition was refractory to corticosteroids and oral immunosuppressants were treated with intravenous cyclophosphamide (0.5 to 1.0 g/m2) monthly for 6 months. RESULTS: All patients had bilateral eye involvement. One eye was legally blind, and 13 eyes could see only hand movements or count fingers. Six patients had evidence of the secondary antiphospholipid antibody syndrome. Complete recovery in visual acuity occurred in 10 eyes (50%), and a partial response occurred in six eyes (30%); four eyes (20%) had no response. Complete response in the field tests occurred in eight eyes (40%), with a partial response in nine eyes (45%); no improvement occurred in three eyes (15%). CONCLUSIONS: Intravenous cyclophosphamide pulse therapy seems to be an effective treatment for optic neuritis refractory to corticosteroids, oral immunosuppressants, or both. A randomized controlled trial will be necessary to confirm our results.

Adolescent↗
PubMedDate not supplied

Candida albicans infection enhances immunosuppression induced by cyclophosphamide by selective priming of suppressive myeloid progenitors for NO production.

Systemic infections caused by fungi after cytoreductive therapies are especially difficult to deal with in spite of currently available antimicrobials. However, little is known about the effects of fungi on the immune system of immunosuppressed hosts. We have addressed this by studying the in vitro T cell responses after systemic infection with Candida albicans in cyclophosphamide-treated mice. After cyclophosphamide treatment, a massive splenic colonization of the spleens, but not lymph nodes, by immature myeloid progenitor (Ly-6G(+)CD11b(+))cells is observed. These cells are able to suppress proliferation of T lymphocytes via a nitric oxide (NO)-dependent mechanism. Systemic infection with a sublethal dose of C. albicans did not cause immunosuppression per se but strongly increased NO-dependent suppression in cyclophosphamide-treated mice, by selective priming of suppressive myeloid progenitors (Ly-6G(+)CD11b(+)CD31(+)CD40(+)WGA(+)CD117(low/-)CD34(low/-)) for iNOS protein expression. The results indicate that systemic C. albicans infection can augment the effects of immunosuppressive therapies by promoting functional changes in immunosuppressive cells.

Animals↗
PubMed1974

Cyclophosphamide and the prepubertal gonad: a negative report.

Serum determinations of follicle-stimulating hormone and luteinizing hormone have been carried out in 13 prepubertal and adult patients who had been treated with courses of either oral or intravenous cyclophosphamide. All results were within the normal range for the patients' ages and sexual development. Although these results establish that gonadal endocrine function and pituitary-gonadal feedback relations may not be destroyed by cyclophosphamide, the possibility remains that prolonged cyclophosphamide therapy in young patients will result in some impairment of future fertility.

Adolescent↗
PubMed1977

Postpubertal evaluation of gonadal function following cyclophosphamide therapy before and during puberty.

Evaluation of pituitary gonadotropins, gonadal steroids, spermatogenesis, and menstrual function was undertaken in 32 patients (19 males and 13 females) treated with cyclophosphamide because of nephrotic syndrome. Patients were treated before, during, or after puberty. Evaluations took place after or in very late puberty. Spermatogenic dysfunction occurred in six of 15 boys who received the entire course before and during puberty and was probably dose related. Menstrual dysfunction did not occur following treatment of six prepubertal or pubertal girls, though only low total doses were used. Therapy after puberty was associated with spermatogenic dysfunction in all four boys, but did not cause menstrual dysfunction in any of seven women. Tentative guidelines are suggested that many minimize gonadal toxicity when cyclophosphamide is used in children with nephrotic syndrome. Factors of particular importance in the interpretation of gonadotropin determinations and of sperm counts in young cyclophosphamide-treated patients are discussed.

Cyclophosphamide↗
PubMed1998

Bladder cancer in patients with multiple sclerosis treated with cyclophosphamide.

PURPOSE: We define the risk of bladder cancer in multiple sclerosis related to the use of indwelling catheters and cyclophosphamide administered as an immunomodulating agent. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,351 patients with multiple sclerosis referred to the National Center for Multiple Sclerosis. RESULTS: Of the 2,351 patients 2 women and 5 men (0.29%) had bladder cancer. Of the 850 chronically catheterized patients the incidence was 0.7%. One patient with cancer performed intermittent catheterization for a rate of 0.23% in this group. In a subgroup of 70 patients treated with cyclophosphamide 5 chronically catheterized patients (5.7%) had bladder cancer. Hematuria was the most common presenting symptom. These data were compared with those in the literature on bladder cancer in spinal cord injury. CONCLUSIONS: These data suggest a possible synergistic role of cyclophosphamide and chronic catheterization in the induction of secondary bladder cancer. Regular cystoscopy is warranted in these patients to allow early detection of bladder tumors. Nitric oxide metabolism may be an important factor in the carcinogenesis of this type of bladder cancer.

Adjuvants, Immunologic↗
PubMed1994

Effect of perioperative chemoimmunotherapy with cyclophosphamide and autologous tumor vaccine in murine MBT-2 bladder cancer.

The in vitro cytotoxic activity of splenocytes from C3H/He mice implanted subcutaneously with 10(6) syngeneic MBT-2 tumor cells on day 0 was significantly enhanced after cyclophosphamide (100 mg./kg., intraperitoneally) given 2 days before tumor resection on day 17, with or without active specific immunization with BCG plus autologous irradiated tumor cells (vaccine) 1 week after tumor resection. Furthermore, a significantly lower tumor incidence was seen in mice challenged with 10(5), but not 10(6), tumor cells per mouse 24 hours after tumor resection on day 17 and treated with cyclophosphamide on day 15 and postoperatively with vaccine than was found in nontreated tumor resected mice. Phenotypic analysis of cells from spleen showed that cyclophosphamide pretreatment and postoperative vaccine, either singly or in combination, induced a significant increase of both CD44+ memory T cells and CD11b+ myeloid/macrophage cells. Thus, in addition to a specific antitumor immune response, a nonspecific cytolytic mechanism may also play a role in the observed antitumor effect.

Animals↗
PubMed1993

Treatment of cyclophosphamide-induced hemorrhagic cystitis with intravesical carboprost tromethamine.

We review our experience with 18 consecutive patients who received intravesical carboprost tromethamine, an F2-alpha prostaglandin, for severe hemorrhagic cystitis following cyclophosphamide chemotherapy. Of the patients 16 were given cyclophosphamide for conditioning before bone marrow transplantation and 2 received the drug as cytotoxic therapy alone (dose range 3.6 to 15.8 gm.). All patients had severe gross hematuria that was refractory to forced diuresis and to continuous saline bladder irrigation. The intravesical prostaglandin therapy was initiated only after significant transfusion requirements (greater than 1 unit packed red blood cells per day) and/or numerous catheter manipulations for relief of clot retention. Eligible patients underwent complete clot evacuation followed by intravesical instillation of 0.4 to 1.0 mg.% carboprost tromethamine for 2 hours 4 times per day, alternating with continuous saline bladder irrigation for 2 hours. Six patients attempted an alternate protocol of 0.8 to 1.0 mg.% carboprost tromethamine given by continuous saline bladder irrigation. Complete resolution of gross hematuria occurred in 9 patients (50%). Eight patients had a partial response, with decreased transfusion requirements noted. However, complete resolution ultimately required an alternative therapy (for example formalin or urinary diversion). One patient (6%) failed to respond and required formalin therapy on day 4 of carboprost tromethamine therapy. Decreased red blood cell transfusion requirements were noted during and after therapy when compared to pretreatment values. No changes in renal or bladder function were noted during the mean followup of 17 weeks (range 1 to 64 weeks). There were 3 cases of recurrent hematuria. Side effects were limited to bladder spasm in 14 of the 18 patients (78%), with no systemic complications. The results suggest that carboprost tromethamine is a useful bedside therapy for hemorrhagic cystitis due to cyclophosphamide, and treatment appears to have minimal toxicity.

Administration, Intravesical↗