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PubMed2000

Steroid and cyclophosphamide in IgA nephropathy.

BACKGROUND: IgA nephropathy is associated with a wide spectrum of possible lesions. Therefore, different responses to anti-inflammatory or immunosuppressive therapies should be expected with acute inflammatory changes, which are predominantly reversible, and with prevalently sclerotic lesions. METHODS: The effects of a combined schedule of prednisone and cyclophosphamide was analysed in the specific subset of IgA nephropathy patients with acute inflammatory histologic changes associated with haematuria and proteinuria. Two groups of patients, with similar histologic lesions and clinical presentation, were considered. The first group (12 patients) was treated within 1 week after renal biopsy; starting with three pulses of methylprednisolone (1 g) followed by oral prednisone (0.8 mg/kg body weight for 2 weeks, 0.6 mg/kg for another 2 weeks, 0.4 mg/kg for an additional 4 weeks, then slowly tapered by 5 mg each month until discontinuation) and 1.5 mg/kg cyclophosphamide for 2 months. A second sample of eight untreated patients served as a control group. Treated and untreated patients had diffuse mesangial proliferation with florid crescents (8-60% in treated and 10-40% in untreated patients) with mild degree of glomerular sclerosis and interstitial changes. Basal creatinine (167 micromol/l, range 79-371 vs 132 micromol/l, range 79-256) and proteinuria (3.0 g/24 h, 1.0-4.9 vs 3.3 g/24 h, 1.0-13.7) were not statistically different between treated and untreated patients respectively. Nine treated and six untreated patients were hypertensive. Blood pressure treatment did not include ACE-inhibitors. RESULTS: Untreated patients' 5-year renal survival, as assessed by the Kaplan-Meier method, was found to be significantly lower than treated patients (37.5 vs 91.6%, log-rank P=0.01 and Breslow test P=0.008; relative risk to reach the endpoint of a 100% increase in serum creatinine=3.58, P=0.03). CONCLUSION: This short course of therapy with prednisone and cyclophosphamide has been effective in a subset of IgA nephropathy patients with florid glomerular changes and major urinary abnormalities, turning off phlogistic activity and preventing subsequent progression toward renal failure.

Adolescent↗
PubMed1991

Treatment of rapidly progressive glomerulonephritis by extracorporeal immunoadsorption, prednisolone and cyclophosphamide.

Ten patients with rapidly progressive glomerulonephritis and acute renal failure were treated with extracorporeal immunoadsorption, prednisolone, and cyclophosphamide. Three patients had systemic lupus erythematosus, five had microscopic polyarteritis and two had Wegener's granulomatosis. All ten patients were dialysis-dependent prior to immunoadsorption. Nine of ten patients rapidly regained renal function and seven continue to have independent renal function between 9 and 30 months after immunoadsorption. Three patients at presentation were not dialysis dependent. Despite treatment with methylprednisolone, cyclophosphamide, and oral prednisolone, renal function continued to deteriorate and they required dialysis. Immunoadsorption was then started without alteration in baseline immunosuppression. Within a mean of 4.6 days, range 3-7 days, renal function improved and the patients no longer required dialysis. Antineutrophil cytoplasmic antibodies and double-stranded DNA antibodies were rapidly removed by immunoadsorption. Only one patient with systemic lupus erythematosus and two with microscopic polyarteritis had significant resynthesis of antibody at 1 month post-immunoadsorption. Renal biopsy before and after immunoadsorption and immunosuppressive therapy showed resolution of glomerular crescents and no evidence of active disease. Immunoadsorption coupled with prednisolone and cyclophosphamide may be of value in the treatment of rapidly progressive glomerulonephritis.

Adult↗
PubMed2003

Crescentic, proliferative IgA nephropathy: clinical and histological response to methylprednisolone and intravenous cyclophosphamide.

BACKGROUND: IgA nephropathy is an immune-complex glomerulopathy that can result in capillary or extra-capillary proliferation. Previous attempts to correlate specific histological findings including cellular crescents or endocapillary proliferation, with clinical outcomes, have produced conflicting results. METHODS: We conducted a prospective open-labelled trial of 12 patients with crescentic, proliferative IgA nephropathy and clinically progressive disease and treated them with pulse steroids and intravenous cyclophosphamide. Therapy included pulse solumedrol at 15 mg/kg/day for 3 days, followed by monthly intravenous cyclophosphamide at 0.5 g/m(2) body surface area for 6 months. Clinically significant proteinuria (>1.0 g/24 h) was present in all patients, while nephrotic-range proteinuria (>3.0 g/24 h) was observed in eight of 12 patients. All patients were hypertensive (BP >140/90 mmHg). RESULTS: After 6 months of treatment, the mean serum creatinine was reduced from a maximum of 2.65+/-0.39 to 1.51+/-0.10 mg/dl (P<0.03), while proteinuria was reduced from 4.04 to 1.35 g/24 h (P<0.01). The mean slope of 1/serum creatinine increased from -0.0398+/-0.02 to 0.0076+/-0.01 after 6 months of therapy, but this trend did not reach statistical significance (P<0.08). A repeat kidney biopsy was performed in all treated patients. Endocapillary proliferation, cellular crescents and karyorrhexis were eliminated in all 12 patients after 6 months of therapy, while interstitial fibrosis and tubule dropout remained unchanged. To determine the long-term efficacy of the treatment, treated patients were compared to 12 historical controls matched for severity of IgA on initial biopsy. After 36 months, the rate of end-stage renal disease in the treated group was lower (1/12) than in the historical controls (5/12). CONCLUSIONS: We conclude that steroids and intravenous cyclophosphamide reduce proliferative lesions, reduce proteinuria and stabilize renal function in patients with crescentic IgA nephropathy.

Adult↗
PubMed1996

Dose-intensive chemotherapy with doxorubicin, cyclophosphamide and GM-CSF fails to improve survival of metastatic breast cancer patients.

BACKGROUND: A dose response relationship for doxorubicin and cyclophosphamide has been suggested. In a previous dose finding study we treated advanced breast cancer patients with escalating doses of doxorubicin and cyclophosphamide in combination with GM-CSF. The aim of this study is to further define the acute and cumulative toxicity of this treatment in relation to its antitumor activity. PATIENTS AND METHODS: Twenty-eight patients with metastatic breast cancer were treated with doxorubicin (90 mg/m2) and cyclophosphamide (1000 mg/m2) at 3-week intervals. Dose reductions of 10% were applied in the second and fourth cycles. On the second day GM-CSF was started at 250 mu g/m2 daily for 10 days. The intention was to give 6 cycles, but when a complete remission was reached earlier only one more cycle was given as consolidation. RESULTS: The median number of cycles was 5 (range 2-6). Twenty-three patients responded (82%, 95% CI 69%-97%), with 9 of them achieving a complete response (32%, 95% CI 14%-50%). For the 18 patients evaluable for time to progression and survival the median time to progression was 8 months and the median survival 14.5 months. Toxicity was substantial: grades 3 or 4 neutropenia occurred in 95% of cycles and grades 3-4 thrombocytopenia in 49% of cycles. Grade 3-4 mucositis was present in 13% of the cycles. Weakness and fatigue were always present and were cumulative. Four patients had a decline in the left ventricular ejection fraction (LVEF). These side effects were the reason for discontinuing therapy in 9 of the 28 patients (32%). CONCLUSION: This treatment has a high response rate in comparison with conventional-dose chemotherapy but does not prolong time to progression or survival. The toxicity makes this protocol unsuitable for use as palliative treatment.

Adult↗
PubMed1993

Recombinant human interleukin-3 hastens trilineage hematopoietic recovery following high-dose (7 g/m2) cyclophosphamide cancer therapy.

BACKGROUND: Interleukin-3, a recombinant cytokine with multilineage stimulatory effect on hematopoietic cells, was administered to 22 previously untreated breast cancer patients following high-dose therapy with cyclophosphamide (7 g/m2). PATIENTS AND METHODS: The growth factor, administered through continuous intravenous infusion at 1 (3 patients), 2.5 (3 patients), 5 (10 patients) and 10 micrograms/kg/day (6 patients), was well tolerated up to 5 micrograms/kg/day. RESULTS: Nausea, vomiting, fever and headache prevented administration of the intended dose to all 6 patients in the 10 micrograms/kg/day cohort. At the maximal tolerable dose (5 micrograms/kg/day) the growth factor significantly accelerated granulocyte, platelet and reticulocyte recovery as compared to matched historical controls who received high-dose cyclophosphamide without cytokine infusion. Moreover, no platelet transfusions and fewer erythrocyte transfusions were required in interleukin 3-treated patients. In contrast to GM-CSF and G-CSF, interleukin 3 showed no effect on the mobilization of hematopoietic progenitor cells in the peripheral blood. CONCLUSIONS: Interleukin-3 represents a well-tolerated cytokine, clinically useful for accelerating trilineage hematopoietic recovery following severely myelotoxic treatments such as high-dose cyclophosphamide.

Adolescent↗
PubMed1997

Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis.

Although cyclophosphamide and prednisolone are effective in treating systemic vasculitis, the optimum treatment regimes and duration of treatment are unknown. We randomized 54 patients aged 15-70 years (median 57.5 years) with systemic vasculitis (classical polyarteritis n = 8, microscopic polyarteritis n = 17, Wegener's granulomatosis n = 29) to treatment with either pulse cyclophosphamide and prednisolone (PCYP) (n = 24) or continuous oral and prednisolone and cyclophosphamide, with the latter followed after a median of 3 months (range 1.5-10 months) by azathioprine (CCAZP) (n = 30). Patients on CCAZP were more likely to develop leucopenia (13/30) than patients on PCYP, (7/24) although the difference was not significant. The numbers of infective episodes during follow up were comparable in the two groups at 1.7/patient for PCYP and 1.66/patient for CCAZP. Overall, 26/30 patients (87%) treated with CCAZP developed treatment-related toxicity, as did 17/24 patients (71%) treated with PCYP. After a median follow-up of 40.4 months (range 0.7-64.8), there was no difference in the frequency of deaths (PCYP 5, CCAZP 4), relapses (PCCYP 7, CCAZP 8), treatment failures (PCYP 4, CCAZP 4), improvement in disease activity scores or renal function. Survival at three years was 77% in patients treated with PCYP, and 90% in patients on CCAZP (p = 0.38). There was a tendency towards increased toxicity in patients treated with the continuous regimen.

Adolescent↗
PubMed1998

Successful treatment of gastrointestinal vasculitis due to systemic lupus erythematosus with intravenous pulse cyclophosphamide: a clinical case report and review of the literature.

Gastrointestinal vasculitis in systemic lupus erythematosus (SLE) is quite rare and almost always accompanied by evidence of active disease in other organs, although occasionally it may be the presenting feature of the disease. Gastrointestinal involvement in SLE may present as lupus peritonitis, non-necrotizing pancreatitis, gastrointestinal vasculitis or surgical abdomen. Here we report a severe case of SLE which presented initially with fever of unknown origin. Severe distress, abdominal pain, the presence of occult blood in the stool and high acute-phase proteins were explained by a lupus peritonitis and intestinal vasculitis resembling inflammatory bowel disease. Whereas high-dose prednisone treatment did not prevent a severe relapse, we observed a sustained remission following i.v. cyclophosphamide pulse therapy. In the literature, only two similar cases are reported: one died despite a change in the therapy of a bowel perforation; our case was the second that improved under pulse cyclophosphamide. We suggest the use of cyclophosphamide after failure of steroids early in the course of SLE gastrointestinal vasculitis to prevent devastating complications.

Abdominal Pain↗
PubMed1988

Phase II trial of recombinant alpha-2b-interferon and low-dose cyclophosphamide in advanced melanoma and renal cell carcinoma.

The combination of Interferon and low-dose cyclophosphamide synergistically inhibits the growth of human breast cancer xenografts, explanted human non-small cell lung carcinoma, and other experimental tumors. To determine whether this combination would demonstrate clinical efficacy against refractory solid tumors, we used recombinant alpha-2b-Interferon, 10 MU/m2 subcutaneously three times per week, and cyclophosphamide, 25 mg orally twice daily, in 42 patients (25 renal cell carcinoma, 17 melanoma). Two patients were inevaluable due to premature removal from the study. The toxicity profile did not differ substantially from that of Interferon alone with malaise, fatigue, fevers, and chills predominating. Sixteen percent of patients experienced an alteration in mental status. Of 40 patients evaluable for response, there were two partial responders (one renal cell carcinoma, one melanoma) and four minor responders (all renal cell carcinoma). The responder with melanoma had previously failed therapy with dacarbazine (DTIC). Seventeen patients remained stable for a median follow-up of 6 months. We conclude that this regimen is well tolerated; however, the combination of Interferon and low-dose cyclophosphamide used in this way does not appear to be superior to the same dose and schedule of Interferon used alone.

Administration, Oral↗
PubMed1995

Impact on progression-free survival of adjuvant cyclophosphamide, vincristine, doxorubicin (adriamycin), and dacarbazine (CYVADIC) chemotherapy for stage I uterine sarcoma. A prospective trial.

To assess the impact on progression-free survival of the use of the multiagent chemotherapy regimen of cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dacarbazine (CYVADIC) as adjuvant treatment for patients with stage I uterine sarcoma: 20 evaluable patients who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for stage I uterine sarcoma received adjuvant multiagent chemotherapy with vincristine sulfate 1 mg/m2 days 1 and 4, doxorubicin (Adriamycin) 40 mg/m2 and cyclophosphamide 400 mg/m2 day 2, and dacarbazine 200 mg/m2 days 1 through 4 for a total of 9 monthly cycles or until recurrence of disease was documented. Patients were followed for a median of 65 months (range: 5-116 months). Myelotoxicity was monitored by weekly complete blood counts, cardiac toxicity by monthly radionuclide angiography, and neurotoxicity by monthly physical examination. Survival and progression-free survival were calculated by the method of Kaplan and Meier (17). The Fisher exact test was employed to determine the significance of recurrence rates between histologic groups (18). These 20 patients received 172 of a planned 180 cycles of chemotherapy. Dose reductions in response to myelotoxicity were necessitated in four cycles among three patients. Mild neurotoxicity was observed in six patients (30%) and moderate neurotoxicity in one patient (5%). A decrease in cardiac ejection fraction of > 10% was observed in two patients (10%). No deaths ascribable to complications arising from chemotherapy were observed. Seven patients (35%) developed recurrence of disease. Recurrence rates for pure sarcomas and mixed mesodermal tumors did not differ significantly (P = .65). Progression-free survival for the population at 2 years was 80% and at 5 years was 65%. This study describes the largest prospective trial of adjuvant combination chemotherapy for patients with stage I uterine sarcoma reported to date. Adjuvant chemotherapy employing the combination of cyclophosphamide, vincristine, doxorubicin (Adriamycin), and dacarbazine (CYVADIC) failed to impact significantly on long-term survival in this group of patients with stage I uterine sarcoma.

Adult↗
PubMed1996

Intermediate doses of cyclophosphamide alone or following adriamycin in advanced breast cancer. A pilot study.

Cyclophosphamide (CTX) is an active drug in breast cancer and presents a well-established dose-response relationship. To explore further this relationship, the present pilot study investigated the therapeutic efficacy of cyclophosphamide at intermediate dose in two groups of untreated patients with advanced breast cancer. Nine women received the drug alone at 3-4 g/m2 i.v. every 2 weeks for a total of three doses. The same dose schedule was also given to 11 women following the administration of four cycles of Adriamycin, at 75 mg/m2 i.v. every 3 weeks. We documented one partial remission in untreated women and four partial responses in Adriamycin-treated patients. The major toxicity was represented by leukopenia and neutropenia. Myelosuppression was relevant but of short duration, and the use of G-CSF appeared useful in controlling this side effect. In spite of the high dose intensity of the present cyclophosphamide dose schedule (9 g/m2 in 4 weeks), i.e., almost three times superior to that conventionally employed, present results do not suggest its superiority over the current chemotherapeutic regimens utilized in advanced disease.

Adult↗
PubMed1996

High-dose cyclophosphamide, carboplatin, and etoposide with autologous stem cell rescue in patients with breast cancer.

This study was designed to establish the toxicity and response rates o observed with a combination of high-dose cyclophosphamide, carboplatin, and etoposide with stem cell rescue in patients with breast carcinoma. Eligibility criteria included metastatic or locally advanced breast carcinoma ; aged < or equal to 60 years; performance status Eastern Cooperative Oncology Group (ECOG) 0-1; and creatinine clearance > or equal to 65 ml/min. Chemotherapy consisted of cyclophosphamide 25 mg/kg i.v. X 4 days, etoposide 400 mg/m(2) i.v. X 4 days, and carboplatin 375 mg/m(2) X 4 days. Bone marrow or peripheral blood stem cells were reinfused 48 h after completion of chemotherapy. Seventeen patients were treated in this study. The major toxicity was gastrointestinal (grades I and II). Fevers associated with neutropenia were observed in all the patients, but no episodes of bacteremia were documented. Hematopoietic toxicities were acceptable. No toxic deaths were observed. Six patients had chemotherapy-sensitive disease at time of transplant, nine had refractory disease, and two were untested. A response rate of 62% with 18% complete response (CR) was achieved. Two patients are free of disease at +7 and +9 months after transplantation. The combination of high-dose cyclophosphamide, carboplatin, and etoposide is well tolerated with a response rate comparable to previously reported high-dose chemotherapy regimens. However, in a poor prognostic risk group, namely patients with chemoinsensitive disease, this therapeutic approach seems to be of no advantage over standard chemotherapy.

Adult↗
PubMed2000

Hepatic angiosarcoma occurring after cyclophosphamide therapy: case report and review of the literature.

A 54-year-old man with polyarteritis nodosa developed acute onset of right upper quadrant abdominal pain associated with a large liver mass. Transvenous liver biopsy revealed hepatic angiosarcoma, a rare liver tumor classically associated with environmental toxins. He had been treated with oral cyclophosphamide for 13 years. A review of the literature revealed two other cases of hepatic angiosarcoma in patients after long-term cyclophosphamide treatment. We propose that cyclophosphamide be added to the list of exposures potentially associated with hepatic angiosarcoma.

Cyclophosphamide↗
PubMed2002

The combination of fludarabine and cyclophosphamide results in a high remission rate with moderate toxicity in low-grade non-Hodgkin's lymphomas.

We undertook a prospective study to evaluate the role of the combination of fludarabine and cyclophosphamide in patients with low-grade non-Hodgkin's lymphoma. Twenty-seven patients with low-grade non-Hodgkin's lymphoma were treated with i.v. fludarabine (30 mg/m ) and cyclophosphamide (250 mg/m ) on days 1-3. Cycles were given at 4-week intervals for a maximum of six courses. Fourteen patients (52%) were previously untreated, 13 patients (48%) had been treated with at least one chemotherapy regimen before. Of the 27 patients, 11 (41%) obtained a complete and 13 (48%) a partial remission, thus the overall response rate was 89%. The remission rate in untreated patients was slightly higher than in pretreated patients (93 versus 85%). The toxicity was mild, no treatment-related mortality occurred. Neutropenia was the most common side effect, grade 4 neutropenia of rather short duration was observed in less than 7% of the cycles. At the end of the treatment, the mean CD4 count was 155/ l and the mean CD8 count 204/ l. Severe infections did not occur. These results show that the combination of fludarabine and cyclophosphamide in the doses used in this study is an effective regimen with manageable toxicity in low-grade non-Hodgkin's lymphoma.

Adult↗
PubMed1992

Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer.

We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone.

Adolescent↗
PubMed1995

Prevention of hemorrhagic cystitis following allogeneic bone marrow transplant preparative regimens with cyclophosphamide and busulfan: role of continuous bladder irrigation.

High dose cyclophosphamide and/or busulfan conditioning treatment of recipients of bone marrow transplants proved to be highly effective but associated with substantial and sometimes life threatening hemorrhagic cystitis. To prevent this complication, a prophylactic continuous bladder irrigation program was instituted in patients receiving cyclophosphamide and/or busulfan in preparation for bone marrow transplantation. Retrospective analysis of 199 patients who underwent allogeneic bone marrow transplantation revealed that continuous bladder irrigation significantly decreased the frequency of hemorrhagic cystitis in patients receiving busulfan and cyclophosphamide (continuous bladder irrigation 23% versus no bladder irrigation 53%, p < 0.004). There was no difference in the frequency of hemorrhagic cystitis between the different preparative regimens in patients who underwent continuous bladder irrigation. There was no relationship between the incidence of hemorrhagic cystitis and the severity of graft-versus-host disease or the time to engraftment. The duration of hemorrhagic cystitis and overall survival rates were similar in both groups, and there was no increase in complications related to catheterization. In general, continuous bladder irrigation was well tolerated, decreased the incidence of hemorrhagic cystitis and may be useful in bone marrow transplant patients.

Adolescent↗
PubMed2005

Alteration of the organ uptake of the (99m)Tc-radiopharmaceuticals, (99m)Tc-DPD, (99m)Tc-DMSA, (99m)Tc-tin colloid and (99m)Tc-MAA, induced by the applied cytotoxic drugs methotrexate sodium and cyclophosphamide.

AIM: To investigate the influence of certain cytotoxic drugs on the organ uptake of the following (99m)Tc-radiopharmaceuticals: (99m)Tc-2,3-dicarboxypropane-1,1-diphosphonic acid ((99m)Tc-DPD), (99m)Tc-meso-2,3-dimercaptosuccinic acid ((99m)Tc-DMSA), (99m)Tc-tin colloid and (99m)Tc-macroaggregated albumin ((99m)Tc-MAA). Methotrexate sodium and cyclophosphamide were used as models to evaluate these effects. METHODS: Two groups of healthy male Wistar rats were treated separately by oral application of the drugs for 7 days. On the eighth day, each of the (99m)Tc-radiopharmaceuticals was applied in a separate group of treated animals. They were sacrificed at different time intervals and the radioactivity in the organs of interest was measured. The organ uptake of the (99m)Tc-radiopharmaceuticals in an additional control group of animals was also studied. RESULTS: The results obtained showed an alteration in the organ uptake of (99m)Tc-radiopharmaceuticals in animals treated with cytotoxic drugs. In rats treated with methotrexate sodium, there was a higher uptake of (99m)Tc-DMSA in the bones, stomach and intestine, a higher uptake of (99m)Tc-DPD in the bones, intestine, blood and muscle, a lower uptake of (99m)Tc-tin colloid in the liver and a lower accumulation of (99m)Tc-MAA in the lungs. Cyclophosphamide-treated animals showed enhanced uptake of (99m)Tc-DMSA in the kidneys, a twofold enhanced uptake of (99m)Tc-DPD in all organs except the stomach, a decreased uptake of (99m)Tc-tin colloid in the lungs, spleen and kidneys and a significantly decreased uptake of (99m)Tc-MAA in the lungs. CONCLUSION: These results confirm that both methotrexate sodium and cyclophosphamide may alter the organ uptake of (99m)Tc-radiopharmaceuticals in experimental animals.

Animals↗
PubMed1984

High-performance liquid chromatographic measurement of cyclophosphamide in serum.

The analysis of cyclophosphamide [N,N-bis(2-chlorethyl)-tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine -2-oxide] by high-performance liquid chromatography using ultraviolet detection is described. The method will enable measurement of serum concentrations of cyclophosphamide over a period of approximately 24 h after a dose of 150 mg, and requires 1 ml of serum. The between-day precision of the assay at concentrations of 0.3, 1.0, and 15.0 mg/L generated coefficients of variation of 11.8, 12.2, and 7.7%, respectively. Percentages of analytical recovery of cyclophosphamide and internal standard (5-ethyl-5-p-tolylbarbituric acid) were 63 and 73%, respectively. Preliminary data providing the half-life for two patients with normal renal function are presented.

Chemical Phenomena↗
PubMed1985

Drug-induced tolerance to allografts in mice. IV. Mechanisms and kinetics of cyclophosphamide-induced tolerance.

Mechanisms and kinetics of tolerance in AKR mice induced using i.v. priming with viable C57BL/6 spleen cells and treatment with cyclophosphamide 2 days later were analyzed. In this tolerance induction system, some lymphocyte populations mediating delayed foot-pad reaction and cytotoxic activity were resistant to tolerance induction and remained in a sensitized state after cyclophosphamide treatment. These populations were considered to be qualitatively distinct from populations sensitive to cyclophosphamide, because delayed foot-pad reaction and cytotoxic lymphocyte activity were stronger in tolerant mice than in control mice in the early stages of tolerance induction, but were not augmented after immunization with C57BL/6 spleen cells, C57BL/6 skin grafts, or EL4 tumor grafts in the absence of suppressor T cells. One of the important differences in these two lymphocyte populations may be the capacity for clonal expansion.

Animals↗