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 1,369 records · Page 76Linked to original sources
PubMed1970

Evaluation of cyclophosphamide dosage schedules in breast cancer.

Dosage recommendations for cyclophosphamide therapy are examined in the light of an accumulated experience that this agent provides a useful palliation in 25% to 35% of patients with advanced breast cancer. It is concluded that an attempt to press dosage to the extreme limits of marrow tolerance does not significantly increase the likelihood of obtaining palliation, while posing a danger to the patient's life.It is also concluded that continuous low dosage schedules appear to achieve a similar incidence of tumour palliation to that from intermittent high dosage of cyclophosphamide. The latter schedule has the disadvantage of a considerably higher incidence of side effects, such as loss of scalp hair, nausea, cystitis and haemopoietic damage. Intensive dosage may however be more efficacious in the occasional case involving urgent management of a localized rapidly growing tumour. Consideration is given to other factors which may affect the degree and duration of palliation by cyclophosphamide, and to measures claimed to decrease the degree of toxicity.

Adrenal Cortex Hormones↗
PubMed1973

A quantitative morphological analysis of the response of a transplantable rat fibrosarcoma to cyclophosphamide.

The response of a transplantable rat fibrosarcoma, RIB(5), to a single injection of 100 mg/kg body weight of cyclophosphamide, 0·5, 1, 2 and 3 days after treatment, has been studied by means of a morphometric analysis of tumour sections and has been compared to the changes occurring in untreated tumours. The results showed a transitory increase in thymidine labelling index 12 hours after drug injection accompanied by a low mitotic index which persisted for a further 12 hours. These observations are compared with, and confirm, a previous study involving analysis of smear preparations from tumour cell suspensions. The changes in the proportion of the tumour occupied by erythrocytes and necrotic elements are described. The results of the morphometric analysis have shown the changes occurring in the outer, intermediate and inner zones of the tumour. In all control tumours, and tumours up to 2 days after cyclophosphamide treatment, necrosis was predominant in the inner zone and tumour cell proliferation was most marked in the outer zone. In contrast, 3 days after cyclophosphamide treatment proliferation was predominant in the inner zone and the amount of necrosis was approximately the same in each zone.

Animals↗
PubMed1975

Stimulation of granulocytic colony formation in agar diffusion chambers implanted in cyclophosphamide pretreated mice.

The growth of mouse bone marrow colonies in agar diffusion chambers (ADCs) was evaluated using host mice injected with saline or with cyclophosphamide (CY) before chamber insertion. The mice pretreated with cyclophosphamide proved more effective hosts than control (saline pretreated) mice, indicating that cyclophosphamide causes the elaboration of a stimulating factor acting on colony precursor cells. Assays of the factor for colony stimulating activity against mouse bone marrow cells in agar culture in vitro suggest that potentiation may be due to a slight temporary increase in the level of colony stimulating factor (CSF) in the chamber environment, although a parallel increase was not detected in the serum. Stem cell recovery from the ADCs, measured by spleen colony formation, suggests that the stimulus may act by increasing differentiation at the level of the pluripotential stem cell.

Animals↗
PubMed1977

Metastasis of a transplantable mammary tumour in rats treated with cyclophosphamide and/or irradiation.

We report observations on the spread by metastasis and infiltration of a transplantable tumour in rats treated by 60Co gamma-irradiation of the primary, irradiation plus parenteral cyclophosphamide, or parenteral cyclophosphamide alone. The proportion of animals with overt disseminated disease and the extent of spread were measured with respect to the time elapsed after implantation and treatment of the primary tumour. The incidence of metastatic disease was broadly similar for all treatment groups, but the extent of dissemination was greater in rats whose treatment included cyclophosphamide.

Animals↗
PubMed1980

Harmful effects of i.v. Corynebacterium Parvum given at the same time as cyclophosphamide in patients with squamous-cell carcinoma of the bronchus.

The effects are reported of a combination therapy of i.v. C. parvum and cyclophosphamide on the survival time and immune responses of patients with inoperable squamous-cell carcinoma of the bronchus. The immune status of the patients was evaluated by determining the antibody response to C. parvum, the E and EAC rosettes, the PHA response of blood lymphocytes, the skin-test reactivity to Candida and PPD, the response to DNCB and the chemotaxis and NBT-dye reduction capacity of neutrophil leucocytes. The survival time of patients treated with the combination therapy was found to be significantly shorter than that of untreated patients and of those receiving cyclophosphamide only. Severe side effects were observed after C. parvum infusions, with no decrease on repeated administration. The effect of C. parvum on the different immune parameters of cyclophosphamide-treated patients was negligible, though there was a normal antibody response to C. parvum.

Aged↗
PubMed1984

Comparison of mesna with forced diuresis to prevent cyclophosphamide induced haemorrhagic cystitis in marrow transplantation: a prospective randomised study.

A prospective randomised study was carried out to compare the effect of mesna (2-mercaptoethane sulphonate sodium) with that of forced diuresis in preventing cyclophosphamide induced haemorrhagic cystitis in marrow transplant recipients. Sixty-one consecutive BMT recipients were randomised for treatment with forced diuresis or mesna. The incidence of macroscopic haematuria was significantly lower in the mesna treated group (chi 2 = 4.03, P less than 0.05). No specific side effects of mesna were detected. The lymphopenia induced by cyclophosphamide in the aplastic recipients was similar in the mesna and forced diuresis groups suggesting that mesna has no effect on the lymphocytotoxic activity of cyclophosphamide, although 6 out of 7 episodes of graft failure documented in the study occurred in mesna treated patients. As a result of this study our present policy is to use mesna in all BMT recipients but to continue careful documentation of the incidence of graft failure.

Adolescent↗
PubMed1987

Risk of leukaemia in ovarian tumour and breast cancer patients following treatment by cyclophosphamide.

A case-control study was conducted to determine whether the development of leukaemia was associated with chemotherapy for neoplasms of the ovary or breast, in a population where most such chemotherapy consisted of cyclophosphamide alone. Cases and controls were identified from the National Cancer Registry of the German Democratic Republic. Cases were women who had developed leukaemia as a second primary after an initial diagnosis, at least one year before, of an ovarian or breast tumour. Controls were patients with an ovarian tumour or breast cancer who had survived to the year when the case developed a leukaemia but who had not themselves developed a second malignancy. Controls were matched to cases by the site of the first primary and its year of diagnosis, as well as year of birth. The relative risk for acute leukaemia following treatment with cyclophosphamide alone was significantly elevated (P less than 0.05), at 14.6 for ovarian tumour patients and 2.7 for breast cancer patients. Among breast cancer patients the increased risk of leukaemia associated with chemotherapy was confined to women who had been under 50 years of age at the time of diagnosis of the breast cancer (for whom the relative risk was 13.1). No excess risk of leukaemia was observed in association with radiotherapy for either ovarian or breast cancer patients. The present findings strongly suggest that cyclophosphamide as a single chemotherapeutic agent is capable of inducing leukaemia in humans.

Acute Disease↗
PubMed1981

Prevention of cyclophosphamide-induced antidiuresis by furosemide infusion.

In patients receiving high-dose cyclophosphamide therapy (HDCPT), urinary flow rate, serum sodium concentration, and renal free-water clearance frequently decrease in the 24 hr after drug. High urinary flow rates, which may minimize other cyclophosphamide-related symptoms, are difficult to achieve in the face of the antidiuretic effect. Five patients receiving a total of 30 doses of HDCPT (greater than 50 mg/kg) were studied to assess the effect of continuous furosemide infusion on cyclophosphamide antidiuresis. In two patients receiving various diuretic regimens, only the continuous infusion of furosemide was associated with maintenance of high urinary flow rates and normal serum sodium concentrations. Four patients studied prospectively while receiving HDCPT maintained renal free-water clearance as well as high constant urinary flow rates and normal serum sodium concentrations. Concurrent studies of furosemide disposition revealed that renal excretion of furosemide was unchanged during the continuous infusion and that the diuretic effect was sustained throughout the therapeutic course. The only furosemide-related side effect identified was hypokalemia, which was easily managed with potassium chloride given intravenously.

Adolescent↗
PubMed1999

Successful peripheral blood stem cell mobilization with etoposide (VP-16) in patients with relapsed or resistant lymphoma who failed cyclophosphamide mobilization.

High-dose chemotherapy (HDCT) followed by autologous blood stem cell transplantation is considered the treatment of choice for patients with relapsed or resistant aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). However, several authors report failure of standard mobilization regimens in 29% to 56% of these patients making the completion of HDCT impossible and as a result, negatively influencing long-term outcome. Thus, effective new regimens for patients failing initial mobilization are needed. Here we report the results of using etoposide as a mobilizing agent in 16 patients with primary resistant or relapsed malignant lymphoma who had failed prior mobilization of peripheral blood stem cells (PBSC) with cyclophosphamide (4 g/m2) followed by G-CSF. The use of etoposide 500 mg/m2 (days 1-4) + G-CSF resulted in the successful collection of adequate numbers of PBSC with a median harvest of 3.6 x 10(6)/kg (range 2.2-12.6) CD34+ cells in all 16 patients. In 7/16 (44%) patients, the target yield of at least 2.0 x 10(6) CD34+ cells was harvested by a single apheresis and the maximum number of separations for all patients was two. No excessive toxicities appeared, allowing all patients to proceed to myeloablative chemotherapy. In addition, median peak values of circulating CD34+ cells were significantly higher after etoposide as compared to cyclophosphamide (49.2/microl vs 4.7/microl; P = 0.0004). These results indicate that etoposide + G-CSF is a highly effective mobilization regimen in patients who have failed cyclophosphamide mobilization.

Adult↗
PubMed1999

Modification of the pharmacokinetics of high-dose cyclophosphamide and cisplatin by antiemetics.

Interpatient variability in exposure to certain chemotherapy agents can influence patient outcome, particularly with high-dose chemotherapy. We evaluated the possibility of a pharmacokinetic (PK) drug-drug interaction between the antiemetic agents and high-dose cyclophosphamide, cisplatin and BCNU (CPA/cDDP/BCNU). Twenty-three self-selected patients treated with high-dose CPA/cDDP/BCNU followed by autologous hematopoietic progenitor cell support (AHPCS) received ondansetron, lorazepam and diphenhydramine as antiemetics. PK parameters for each chemotherapeutic drug in the regimen were compared with those of 129 patients who received exactly the same chemotherapy but an antiemetic regimen substituting prochlorperazine for ondansetron. In addition, we performed a review of the English literature for reported drug-drug interactions between antiemetics and chemotherapy agents that led to modifications in any PK parameters of the chemotherapy agent. Our retrospective study showed that the mean area under the curve (AUC) for both cyclophosphamide (76,600 vs 90,600 microg/ml/min, P=0.001) and cisplatin (525 vs 648 microg/ml/min, P = 0.01) were significantly lower in the ondansetron group when compared with the prochlorperazine group. The AUC for BCNU was not significantly different in both groups (544 vs 677, P = 0.43). We found only one report of modifications of the PK parameters of high-dose chemotherapy agents due to drug-drug interactions with the most commonly used antiemetics in a review of the English literature between 1966 and 1995. We concluded that the AUC of high-dose cyclophosphamide and cisplatin are significantly lower when ondansetron, as opposed to prochlorperazine, is used as the antiemetic. The small sample size and heterogeneity of this group of patients precludes any outcome analysis of pharmacodynamic endpoints such as toxicity or antitumor effect. Nevertheless, the potential for interactions between antiemetics and chemotherapy agents should be taken into account when using different high-dose chemotherapy regimens.

Adult↗
PubMed1999

Acquired pseudocholinesterase deficiency after high-dose cyclophosphamide.

Succinylcholine, a depolarizing neuromuscular blocking agent used in anesthesia is hydrolyzed in the plasma by the enzyme pseudocholinesterase (PSC). Conditions associated with reduced PSC activity lead to sustained action of succinylcholine and result in prolonged apnea. Cyclophosphamide is an inhibitor of PSC and its suppressive effect may be dose-dependent. We report a case of severe PSC deficiency after high-dose cyclophosphamide at 7 g/m2. The patient received succinylcholine during anesthesia 9 h after chemotherapy and developed prolonged apnea. This case highlights the potential risk of drug-induced PSC deficiency and cautions the use of depolarizing muscular relaxants soon after high-dose cyclophosphamide.

Adrenal Gland Neoplasms↗
PubMed2000

A comparative study of sequential priming and mobilisation of progenitor cells with rhG-CSF alone and high-dose cyclophosphamide plus rhG-CSF.

Stem cell mobilisation can be achieved either by administration of rhG-CSF alone or after high-dose cyclophosphamide (HDCy) plus rhG-CSF. We have compared both mobilisation procedures intra-individually in 43 patients with haematological malignancies. Furthermore, the toxicity data were registered. The CD34+ cell yield was higher after mobilisation with HDCy plus rhG-CSF than after rhG-CSF alone in 21 out of 22 patients who were actually harvested after both procedures. If a patient mobilised insufficiently after rhG-CSF alone, the yield of CD34+ cells after the following HDCy priming was lower compared to patients who mobilised sufficiently after rhG-CSF priming alone. In 12 patients with B cell malignancies a reduced number of B cells such as CD10+, CD19+, CD20+ cells in bone marrow as well as in leukapheresis products was observed after HDCy plus rhG-CSF compared to rhG-CSF alone. Toxicity data revealed HDCy as a relatively toxic priming regimen with all patients hospitalised and 74% experiencing neutropenic fever and administration of intravenous antibiotics. In two patients, seizure-like episodes were observed during cyclophosphamide bolus infusion. In conclusion, HDCy increased the yield of CD34+cell and reduced B cells in leukapheresis products indicating reduced tumour cell load compared with rhG-CSF priming alone. The efficacy of HDCy priming is limited by its profound toxicity and morbidity. Studies evaluating efficacy and safety of lower doses of cyclophosphamide are needed. Bone Marrow Transplantation (2000) 26, 717-722.

Adolescent↗
PubMed2001

Amiodarone and cyclophosphamide: potential for enhanced lung toxicity.

Antineoplastic therapy can be associated with drug-induced lung toxicity. With the increasing use of amiodarone for cardiac dysrhythmias there is an increasing possibility of its combined use with chemotherapies for various malignancies. We report a patient on long-term amiodarone who developed biopsy-proven drug-induced lung toxicity after receiving high-dose cyclophosphamide, at a time-frame much shorter than would have been predicted with cyclophosphamide alone. The potential for enhanced lung toxicity secondary to combination of amiodarone and cyclophosphamide is discussed.

Amiodarone↗
PubMed2001

Phase II study of a multi-course high-dose chemotherapy regimen incorporating cyclophosphamide, thiotepa, and carboplatin in stage IV breast cancer.

The purpose of this study was to determine the feasibility and efficacy of multiple courses of high-dose cyclophosphamide, carboplatin and thiotepa with peripheral blood progenitor cell (PBPC) transplantation in women with advanced breast cancer. Forty-one patients with advanced hormone-refractory breast cancer were enrolled in the study. The treatment started with two courses of 5-fluorouracil 500 mg/m(2), epirubicin 120 mg/m(2) and cyclophosphamide 500 mg/m(2) (FE(120)C) followed by PBPC harvesting. The high-dose regimen consisted of three subsequent courses of 'tiny' CTC, cyclophosphamide 4000 mg/m(2), thiotepa 320 mg/m(2) and carboplatin 1060 mg/m(2) (target AUC 13.3 mg/ml/min) (tCTC) divided over 4 consecutive days. The second and third courses were scheduled to begin on day 28 after the previous transplantation. A total of 86 tCTC courses was given to 33 of the 41 enrolled patients. Major toxicities consisted of hemorrhagic cystitis (six patients), prolonged gastro-intestinal toxicity (three patients) and veno-occlusive disease (two patients). There was one therapy-related death (unknown cause). Twenty patients (49%) achieved a complete response, nine (22%) a partial response and three patients stable disease after treatment. The median follow-up of the surviving patients was 43 months (range 25-61). Six patients remain in complete remission beyond 3 years. At 4 years, the progression-free survival (PFS) and overall survival (OS) for the whole patient group were 23 and 30% with a median duration of 12 and 27 months, respectively and for FE(120)C-responsive patients 32 and 36%, respectively with a median duration of 15 and 33 months. In the patient group with a PFS > or = 18 months all patients had limited disease (metastatic disease in only one or two sites) and fewer patients had bone or liver metastases compared to the overall patient group (33% vs 51%). This report shows that three closely spaced courses of tCTC are feasible, with acceptable toxicity. Triple tCTC can achieve complete or partial remission in most patients and long-term PFS in a selected subgroup of patients who have limited metastatic disease and are responsive to conventional-dose chemotherapy.

Adult↗
PubMed2004

A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone.

We conducted a prospective randomised study to compare the efficiency of out-patient progenitor cell mobilisation using either intermediate-dose cyclophosphamide (2 g/m(2)) and lenograstim at 5 micrograms/kg (Cyclo-G-CSF group, n=39) or lenograstim alone at 10 micrograms/kg (G-CSF group, n=40). The end points were to compare the impact of the two regimens on mobilisation efficiency, morbidity, time spent in hospital, the number of apheresis procedures required and engraftment kinetics. Successful mobilisation was achieved in 28/40 (70%) in the G-CSF group vs 22/39 (56.4%) for Cyclo-G-CSF (P=0.21). The median number of CD34+ cells mobilised was 2.3 x 10(6)/kg and 2.2 x 10(6)/kg for G-CSF and cyclo-G-CSF arms following a median of two apheresis procedures. Nausea and vomiting and total time spent in the hospital during mobilisation were significantly greater after Cyclo-G-CSF (P<0.05). Rapid neutrophil and platelet engraftment was achieved in all transplanted patients in both groups. In conclusion, G-CSF at 10 micrograms/kg was as efficient at mobilising progenitor cells as a combination of cyclophosphamide and G-CSF with reduced hospitalisation and side effects and prompt engraftment. When aggressive in-patient cytoreductive regimens are not required to both control disease and generate progenitor cells, the use of G-CSF alone appears preferable to combination with intermediate-dose cyclophosphamide.

Adjuvants, Immunologic↗
PubMed2004

Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia.

Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing GVHD and rejection of organ transplants. As the fludarabine-based conditioning regimens without total body irradiation have been reported to be promising for bone marrow transplantation (BMT) from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in unrelated BMT. Five patients underwent BMT with cyclophosphamide (50 mg/kg once daily i.v. on days -9, -8, -7 and -6), fludarabine (30 mg/m2 once daily i.v. on days -5, -4, -3 and -2) and thymoglobulin (2.5 mg/kg once daily i.v. on days -3, -2 and -1) from HLA-matched unrelated donors. Complete donor type hematologic recovery was achieved in all patients. No serious complication occurred during BMT. Only one patient developed grade I acute GVHD resolved spontaneously. Except for one who had rupture of hepatic adenoma 78 days after BMT, all the other four patients are still alive with median 566 days. Fludarabine, cyclophosphamide plus thymoglobulin conditioning allows for the promising results of good engraftment, tolerable toxicity and minimal GVHD.

Adolescent↗
PubMed2003

Phase II study of cyclophosphamide, interferon-alpha and betamethasone (CIB) as induction therapy for patients 60-75 years of age with multiple myeloma stages II and III.

Cyclophosphamide, interferon-alpha and betamethasone are all effective agents for the treatment of multiple myeloma (MM) with different mechanisms of action. The clinical effect of a combination of cyclophosphamide 725 mg/m(2) i.v. days 1 and 3, interferon-alpha 7 x 10(6) IE/m(2) s.c./day, days 1-4 and betamethasone 30 mg orally days 1-4 (CIB) was studied in patients aged 60-75 years with previously untreated MM stages II and III. Granulocyte-macrophage colony-stimulating factor (GM-CSF) 5 microg/kg/day s.c. was administered to all patients from day 5 until the day the granulocyte count exceeded 1.0 x 10(9)/l. CIB was repeated every fourth week. Interferon-alpha 3 x 10(6) IE s.c. t.i.w. was given as maintenance therapy in responding patients.A total of 28 patients (median age: 67 years) entered the study. In all, 12 patients had stage II and 16 had stage III MM. A total of 22 patients (79%) showed an objective response, including five complete remissions (CR) and 17 partial remissions (PR). All seven patients with Bence-Jones MM responded (five CR and two PR). The median response duration time was 14 months (range 5-38+). CIB was relatively well tolerated although febrile neutropenia or septicaemia occurred in 5% of the cycles and a dose-reduction of cyclophosphamide due to grade IV neutropenia was performed in 11% of the patients.CIB seems to be an effective regimen for remission induction in MM patients aged up to 75 years as an alternative to VAD (vincristine, doxorubicin, dexamethasone) if a regimen with intensity higher than that of oral melphalan/prednisone is warranted.

Aged↗
PubMed2001

A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma.

BACKGROUND: The combination of fludarabine and cyclophosphamide shows synergistic toxicity in vitro and has been used to treat nodal non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukaemia. OBJECTIVES: To test the efficacy of this combination in 12 patients with cutaneous T-cell lymphoma (CTCL). METHODS: Nine patients with erythrodermic CTCL were identified for the study, eight of whom met the criteria for Sézary syndrome (SS), and three with tumour-stage mycosis fungoides (MF). Patients received intravenous fludarabine and cyclophosphamide 3 days monthly for 3-6 months. RESULTS: Six patients tolerated at least three cycles. Five with SS had a response (one had a complete clinical response and four a partial response) and one patient with MF had stable disease. The mean duration of the response was 10 months. Six patients had treatment withdrawn, five due to bone marrow suppression and one due to progressive disease. No difference in pretrial parameters were found in those who had treatment withdrawn and those who tolerated at least three courses. Survival since the trial was similar in both groups at 11 months. CONCLUSIONS: These data indicate that the combination of fludarabine with cyclophosphamide may be of clinical benefit in patients with SS but does not affect patient survival. As with other multiagent chemotherapy regimens, bone marrow toxicity is a common and severe side-effect. These data suggest that this regimen should be considered palliative and should be reserved for patients with refractory disease without bone marrow suppression.

Aged↗