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PubMedDate not supplied

High dose cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (rhG-CSF) in the treatment of follicular, low grade non-Hodgkin's lymphoma: CALGB 9150.

The main objectives of this study were to determine the feasibility of administering high doses of cyclophosphamide plus recombinant human granulocyte-colony stimulating factor (rhG-CSF) every 14-21 days to patients with follicular small cleaved cell lymphoma. For each patient, the treatment was not considered feasible if fewer than four cycles of cyclophosphamide chemotherapy could be administered on schedule (i.e. at least every 29 days) or (1) hospitalization of the patient for longer than three days was necessary for neutropenic fever (38 degrees C) or bacteriologically documented infection in > 50% of the cycles, or (2) grade > or = 2 hemorrhage in association with thrombocytopenia of grade > or = 3 severity occurred in > 50% of the cycles or (3) non-hematologic toxicity (excluding nausea/vomiting and alopecia) of grade > or = 3 occurred in > 50% of cycles. The goal was to have a treatment program feasible in 75% or more of the treated patients. The secondary objectives were to determine the toxicities, the complete and partial response rates, and the time to treatment failure (TTF). The trial also attempted to assess the effectiveness of this treatment program in eradicating Bcl-2 rearrangements by PCR, and to assess complete remission duration in relationship to PCR results in patients who respond to this chemotherapy program. Patients were required to have histologically documented non-Hodgkin's lymphoma of the subtypes follicular, predominantly small cleaved cell (IWF-B) or follicular mixed, (IWF-C). Patients were required to have Stage IV disease including histologic evidence of bone marrow involvement. Measurable disease was required and patients were also required to have one of the following risk factors: > or = 2 extranodal sites, node or nodal group > or = 5 cm. Submission of fresh bone marrow for molecular genetic studies for the presence of Bcl-2-Ig fusion DNA was mandatory in previously untreated patients. Patients had to be between 18 and physiologic age 55 years (carefully selected patients over age 55 years were also eligible), expected survival > 2 years, performance status 0-1, and have adequate renal, hepatic and bone marrow function, and a cardiac ejection fraction > or = 50%. Cyclophosphamide 4.5 g/m2 i.v. was given with mesna every 14 days with rhG-CSF support. Twenty-nine patients were accrued to this trial. The median follow-up time is 5.0 years, with a range of 2.5-6.7 years. The overall response rate was 75% (9 CRs 37.5%, 9PRs 37.5%). The median duration of survival is 5.53 years. The 1-year estimated probability of freedom from treatment failure was 50% and of survival at 1 year was 92%. No strong association was observed between TTF and age, symptomatic stage, histology performance status, number of extranodal sites or baseline Bcl-2 status. At 3 years the survival of all patients was 78% and failure free survival was 17%. 15 (62%) of the 24 eligible previously untreated patients met the criteria for feasibility specified in the protocol. The 95% CI for the feasibility rate is (44 and 82%). Twenty-two of the 24 (92%) previously untreated patients had specimens submitted for testing for Bcl-2 rearrangements. Thirteen of the 22 (59%) were found to have rearrangements at baseline. Post-treatment specimens were submitted for seven of the 13 patients. Four of the seven converted to Bcl-2 negative following treatment. Eight of 13 Bcl-2 positive patients (62%) had a clinical response to treatment. The 95% exact binomial CI for the total response rate in this subgroup is (28 and 88%). This study demonstrates that repetitive doses of cyclophosphamide at 4.5 g/m2 every two weeks with rhG-CSF support can be administered to selected younger patients with advanced follicular lymphoma with morphologic involvement of the bone marrow with acceptable non-hematologic toxicity.

Adult↗
PubMed1997

The effect of cyclophosphamide on Fas-mediated apoptosis.

Fas is a cell surface protein that can mediate apoptosis and belongs to the tumor necrosis factor (TNF) receptor family. Anti-Fas antibody induces apoptotic cell death in sensitive cells. Because many chemotherapeutic drugs are capable of initiating pathways leading to apoptosis, we determined the effect of cyclophosphamide, one of the most widely used anticancer drugs, on Fas mediated apoptosis in human lymphoma cell lines; SKW6.4 and Jurkat. Cell lines were cultured for 3 days alone in a medium or with cyclophosphamide (2 micrograms/ml). Anti-Fas IgM of various concentrations was added after treatment. Apoptosis was measured by electrophoresis of DNA fragmentation and surface expression of Fas was measured by flow cytometry. These cell lines were found to express Fas and were very sensitive to anti-Fas induced by cyclophosphamide in Jurkat except SKW6.4. Cyclophosphamide augumented apoptosis mediated by anti-Fas, synergistically. These results suggested that the anti-cancer drug might be mediated via the pathway of Fas mediated apoptosis in the lymphoma cell lines.

Animals↗
PubMed2003

A phase I study of pegylated liposomal doxorubicin hydrochloride (Caelyx) in combination with cyclophosphamide and vincristine as second-line treatment of patients with small-cell lung cancer.

The purpose of this study was to determine the recommended phase II dose of liposomal doxorubicin (Caelyx ; Doxil in the United States) in combination with cyclophosphamide and vincristine for previously treated patients with good performance status with relapsed or refractory small-cell lung cancer. Twenty-one eligible patients were enrolled between November 1999 and September 2001 and received liposomal doxorubicin 25-40 mg/m2, cyclophosphamide 750-1000 mg/m2, and vincristine 1.2 mg/m2 intravenously (I.V.) every 21 days. At doses of liposomal doxorubicin 40 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V., 1 of 6 patients had dose-limiting neutropenia and fever in cycle 2 and 2 of 6 developed grade 3 hand-foot syndrome during cycle 3. Therefore, the recommended phase II doses are liposomal doxorubicin 35 mg/m2, cyclophosphamide 750 mg/m2, and vincristine 1.2 mg/m2 I.V. every 21 days. Antitumor activity was seen at all dose levels. This combination is well tolerated and has evidence of antitumor activity. A phase II evaluation is ongoing.

Adult↗
PubMed1992

Treatment of progressive membranous glomerulopathy. A randomized trial comparing cyclophosphamide and corticosteroids with corticosteroids alone. The Glomerular Disease Collaborative Network.

OBJECTIVE: To determine if deterioration in renal function could be ameliorated by adding cyclophosphamide to corticosteroid therapy in patients with progressive membranous glomerulopathy. DESIGN: Randomized, controlled treatment trial. Patients were followed for a mean of 29.2 +/- 17.1 months. SETTING: Collaborative network of 120 university and private-practice nephrologists. PARTICIPANTS: Patients with membranous glomerulopathy whose renal function deteriorated (as evidenced by doubling of the serum creatinine level, a 50% fall in the glomerular filtration rate, or a sustained serum creatinine level of greater than 2.0 mg/dL [reciprocal creatinine value, 0.5], or whose nephrotic range proteinuria persisted in association with morbid complications. Of 156 patients with biopsy-proven membranous glomerulopathy, 36 became eligible for randomization. Twenty-six of these 36 patients were randomly assigned to receive one of the two treatments. INTERVENTIONS: Pulse methylprednisolone, oral corticosteroids, and 6 months of intravenous cyclophosphamide or alternate-day corticosteroid therapy alone. MAIN RESULTS: At entry, no statistical differences were found between the treatment groups in duration of renal disease, age, gender, serum creatinine level, 24-hour urine protein excretion, or biopsy stage. The groups showed no difference in mean arterial blood pressure during follow-up. Four of the 13 patients receiving corticosteroids alone and 4 of the 13 patients receiving corticosteroids plus intravenous cyclophosphamide progressed to end-stage renal disease during follow-up. Reciprocal creatinine values tested at 6-month intervals showed no statistical differences between treatment groups at any time point. The log of the 24-hour protein excretion values showed no statistical differences between treatment groups after treatment. The power to detect a substantial improvement in renal function, defined as a doubling of the reciprocal of the serum creatinine, at the 0.05 significance level was 0.92. CONCLUSIONS: Combination therapy with intravenous cyclophosphamide and corticosteroids, when compared with corticosteroid therapy alone, does not improve renal function in patients with progressive membranous glomerulopathy.

Adult↗
PubMed1993

Efficacy of oral ondansetron in the prevention of emesis in outpatients receiving cyclophosphamide-based chemotherapy. The Ondansetron Study Group.

OBJECTIVE: To evaluate the efficacy and safety of oral ondansetron (Zofran) as an antiemetic in patients receiving cyclophosphamide-based chemotherapy. DESIGN: A multicenter, randomized, double-blind, stratified, placebo-controlled trial conducted between March 1989 and January 1990. SETTING: Twenty-seven oncology centers including university hospitals, community cancer centers, and private medical oncology practices. PATIENTS: A total of 349 chemotherapy-naive patients having their first cycle of cyclophosphamide (> or = 450 mg/m2)-based chemotherapy. Patients also received methotrexate (> or = 30 mg/m2) or doxorubicin (> or = 35 mg/m2). All patients were evaluated for safety and 318 (91%) were evaluated for efficacy. INTERVENTIONS: Patients were randomly assigned to one of four treatment groups: placebo, 1 mg, 4 mg, or 8 mg of ondansetron. Assigned study medication was taken three times per day for 3 consecutive days. MEASUREMENTS: Time and number of emetic episodes as well as degree of nausea were recorded by patients for each of the 3 study days. RESULTS: Compared with placebo, all three doses of ondansetron were superior (P < 0.001) in preventing vomiting and controlling nausea. A complete response (no emetic episodes) was observed in 19%, 57%, 65%, and 66% of patients in the placebo, 1-mg, 4-mg, and 8-mg ondansetron groups, respectively. For patients who received higher-dose cyclophosphamide and doxorubicin, a dose-related trend in antiemetic efficacy of ondansetron was observed. Mild headache and constipation were the most frequently reported adverse events. No extrapyramidal reactions were observed. CONCLUSION: Oral ondansetron is a safe and effective antiemetic that is more efficacious than placebo for patients receiving cyclophosphamide-based chemotherapy.

Administration, Oral↗
PubMed1980

Rheumatoid vasculitis: effect of cyclophosphamide on the clinical course and levels of circulating immune complexes.

A study of five patients with severe rheumatoid vasculitis treated with cyclophosphamide was undertaken to determine whether immune complexes were present in serum and if their levels correlated with disease activity and response to treatment. Circulating immune complexes were measured by various techniques including the Clq binding and Raji cell radioimmunoassays and determination of the presence of cryoglobulins. Elevated levels of circulating immune complexes, hypocomplementemia, and high titer rheumatoid factor were present during active vasculitis. Clinical and serologic remissions were induced in all patients on cyclophosphamide. In two patients in remission, a rise in rheumatoid factor titer and immune complex levels was associated with an exacerbation of vasculitis and resolved on increased cyclophosphamide dosage. The Clq binding assay and rheumatoid factor titer correlated best with clinical activity. Thus, circulating immune complexes appear to be involved in the immunopathogenesis of rheumatoid vasculitis, which can be successfully treated with cyclophosphamide.

Antigen-Antibody Complex↗
PubMed1997

Immunosurgical studies on cytological and cytogenetic toxicity analysis of rat blastocysts after in vivo exposure to cyclophosphamide.

AIM: To establish immunosurgery and indices of cytogenetic assessment for blastocyst and its inner cell mass (ICM), and to evaluate the toxic effects after in vivo exposure to cyclophosphamide. METHODS: Modified immunosurgery was established by preparation of rabbit-anti-rat spleen antiserum and induction of diluted rat mixed serum as complement. Pregnant rats on d 3 of gestation were injected i.p. cyclophosphamide (10, 20, and 40 mg.kg-1). On d 4, immunosurgery was performed on rat blastocysts. The cell number and the micronuclei of blastocyst and ICM were evaluated respectively. RESULTS: In the cyclophosphamide-treated rats, decreases of cell number (35 +/- 3, 32 +/- 1, 30 +/- 1, and 14 +/- 2, 11 +/- 1, 9 +/- 2) and increases of frequency of micronuclei (1.81%, 2.27%, 3.14%, and 2.53%, 2.98%, 4.75%) in blastocysts and ICM were observed in a dose-related manner. The changes of blastocyst were, however, not parallel to those of ICM which were more serious. CONCLUSION: Modified immunosurgery, an objective and elegant technique, was used on rat blastocysts. In vivo could cyclophosphamide injured ICM more than blastocysts.

Animals↗
PubMedDate not supplied

[Pulsed doses of cyclophosphamide in the treatment of Wegener's granulomatosis].

The aim of the study was to analyze the efficacy and toxicity of the therapy with pulse dose of cyclophosphamide in patients with Wegener's granulomatosis. The diagnosis was established in three patients (2 male, 1 female, average age 58.3 years) upon the clinical picture, laboratory-immunologic and histopathologic findings. The initial therapy was conducted by pulse doses of cyclophosphamide (0.6 and 0.8 g/kg), glucocorticoids (0.5 g), repeated plasmapheresis and pulse doses of immunoglobulin (0.4 g/kg). All patients achieved remission with complete recovery of renal function in one patient. The therapy with pulse doses of cyclophosphamide (time-period between pulses from 1 to 3 months), together with glucocorticoids taken orally for 24 months, was continued for the following 18 months. Stable remission (4-15 months) was maintained in all the patients after the immunosuppressive therapy was over. The treatment of Wegener's granulomatosis by cyclophosphamide and glucocorticoid pulse doses with the application of plasmaphereses and immunoglobulin pulse doses in the initial therapy lead to the remission of progressive types of long duration.

Cyclophosphamide↗
PubMed1999

Role of O6-alkylguanine-DNA alkyltransferase in protecting against cyclophosphamide-induced toxicity and mutagenicity.

Cyclophosphamide is used to treat a wide range of human malignancies. However, it is also a known carcinogen associated with induction of therapy-related leukemia and bladder cancer. The DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), protects cells from the toxic and mutagenic effects of O6-alkylating agents. We report here the contribution of AGT in protecting against the toxic and mutagenic effects of cyclophosphamide. CHO cells transduced with wild-type human AGT (CHO(AGT)) and pcDNA3 (CHOpcDNA3) were treated with activated cyclophosphamide derivatives, 4-hydroperoxycyclophosphamide (4-HC), 4-hydroperoxydidechlorocyclophosphamide (4-HDC), a progenitor of acrolein, and phosphoramide mustard (PM). The results show that CHO(AGT) is 7- or 20-fold less sensitive to the toxic effects of 30 microM 4-HC or 300 microM 4-HDC, respectively, than CHOpcDNA3 cells as measured by cell survival using a colony-forming assay. CHO(AGT) cells treated with 20 microM 4-HC or 200 microM 4-HDC produced 4- or 7-fold lower mutation frequency as measured at the HPRT locus than CHOpcDNA3 cells treated with the same dose of drugs. At 30 microM acrolein, the cell survival for CHO(AGT) was 30% compared with 18.7% for CHOpcDNA3. The mutation frequency of acrolein at the same dose was 57 mutants/10(6) cells in CHOpcDNA3 compared with no mutants in CHO(AGT). In contrast, CHO(AGT) and CHOpcDNA3 cells treated with PM had similar survival curves and exhibited no difference in mutation frequency. The present study demonstrates that AGT plays an important role in protecting against the toxic and mutagenic effect of cyclophosphamide and suggests that acrolein, not PM, is responsible for generating the toxic and mutagenic lesion(s) protected by the AGT protein.

Alkyl and Aryl Transferases↗
PubMed1999

The impact of schedule on acute toxicity and dose-intensity of high-dose chemotherapy with epirubicin and cyclophosphamide plus colony stimulating factors in advanced breast cancer.

To increase the dose-intensity of two drugs in metastatic breast cancer, we tested the feasibility, in phase I studies, of two schedules of epirubicin (E) and cyclophosphamide (C) - sequential (E--> C) and alternating (E/C) - with respect to the standard combination (EC). Drugs were given at three planned-dose levels, plus either G-CSF or GM-CSF. Patients with metastatic (30), inoperable stage IIIb (2) or inflammatory (7) breast cancer were treated. The doses of EC, given every 21 days (4 cycles), were 75/1500, 82.5/2250, 90/3000 mg/m2. In the E/C schedule, epirubicin was given at cycles 1, 3 and 5, and cyclophosphamide at cycles 2, 4 and 6. In the E--> C schedule, three cycles of epirubicin then three cycles of cyclophosphamide were administered. In both experimental schedules, drugs were given every 14 days for 6 cycles at doses of 100, 110, 120 mg/m2 (E) and 2000, 3000, 4000 mg/m2 (C). The average relative dose-intensity was 1.2-fold and 2-fold greater with E/C and E--> C, respectively, than with EC. The third level dose was feasible with all schedules. Grade 4 leucopenia occurred in 77% of patients. Thrombocytopenia was absent in 6 cases and grade 4 in 12 (30.8%). Eighty-one percent of patients on experimental schedules required red blood cell support versus 44.4% of patients on EC. At the third level, platelet transfusions were more frequent among patients treated with EC (27. 8%). Non-haematological toxicity was mild: about 20% of patients experienced grade 3 vomiting, irrespective of schedule. Only 2 patients had grade 3 mucositis; no patient developed heart failure. Fever (61% of patients) and bone pain (55.5% of patients) were relevant in the GM-CSF treated groups and 12 patients shifted to G-CSF. The overall response rate was 84.6%: 5/39 (12.8%) complete response and 28/39 (71.8%) partial response. At 30/9/98, median survival was 29.5 months, with no difference between patients with metastatic and stage IIIb/inflammatory breast cancer. Median follow-up of surviving patients was 62 months (range 17-83). The 5-year estimated survival was 19% (95% confidence intervals = 7-31%). Rapidly alternating or sequential cycles of epirubicin and cyclophosphamide with CSF support is a feasible strategy that allows a higher increase of dose-intensity of the single drugs. Hospitalization and anemia were more frequent with the experimental schedules, and thrombocytopenia with the standard schedule. Overall, this intensified therapy was very active.

Aged↗
PubMed1999

Cyclophosphamide versus ifosfamide: to use ifosfamide or not to use, that is the three-dimensional question.

Ifosfamide and cyclophosphamide are alkylating agents that are extensively used in the clinical treatment of cancer. However, the continued use of ifosfamide has been questioned with the suggestion that cyclophosphamide be used exclusively. One response to this proposal is based upon the fact that both cyclophosphamide and isfosfamide are chiral and are administered as racemic (50:50) mixtures of the two isomers. Studies of the clinical pharmacology, metabolism and disposition of these agents indicate that stereochemistry plays a minor role in the efficacy and toxicity of cyclophosphamide but is a major factor in neurotoxicity associated with ifosfamide administration. Studies have demonstrated that the use of a single ifosfamide enantiomer, (R)-ifosfamide would retain the unique antitumor efficacy of this agent, while eliminating the major source of the observed ifosfamide-associated neurotoxicity, (S)-ifosfamide.

Animals↗
PubMed1999

Effect of pinacidil on the contractile response of cyclophosphamide-treated rat vas deferens.

Effect of pinacidil, a K+ channel opener, was studied on contractility of cyclophosphamide-treated rat vas deferens. The mean IC50 value of pinacidil against 1 mmol barium chloride induced rhythmic contractions and 40 mmol potassium chloride induced tonic contractions was significantly (P < 0.01 and P < 0.001, respectively) increased in the cyclophosphamide treated group as compared to the control. The mean EC50 value of norepinephrine (NE) in the presence of pinacidil (10(-6) mol) was significantly (P < 0.001) increased in the cyclophosphamide treated group. These findings indicate that the responsiveness of rat vas deferens smooth muscle to pinacidil is reduced following cyclophosphamide treatment.

Animals↗
PubMed1999

The efficacy of intravenous pulse cyclophosphamide in the treatment of severe lupus nephritis in children.

BACKGROUND: The intermittent intravenous cyclophosphamide in the treatment of lupus nephritis in adults is well tolerated and associated with clinical improvement and long term stability of renal function. However, there are few reports about the efficacy of intravenous pulse cyclophosphamide (IPC) of severe lupus nephritis in children. OBJECTIVE: To evaluate the clinical efficacy, renal function, renal outcome and complications of IPC therapy in children with severe lupus nephritis. METHOD: Prospective study. PATIENTS: Children with severe lupus nephritis have been followed-up for at least 6 months. Treatment regimen: Intravenous pulse cyclophosphamide 0.5-0.75 g/m2 given monthly for 6 months with subsequent doses given at 2-3 months interval up to 3 years and combined with low dose oral prednisolone therapy. RESULTS: Thirty-one children (mean age: 12.31 +/- 2.03 years; female:male = 24:7) with severe lupus nephritis received IPC therapy. 24 out of 28 patients (85.7%) had diffuse proliferative glomerulonephritis. After 3 months of treatment, most patients were clinically improved as evidenced by significant improvements in 24-hour urine protein, creatinine clearance, serum creatinine, BUN, serum albumin and C3 level. These improvements were sustained up to 18 months and were accompanied by a significant reduction in prednisolone dosage. Renal outcome at the last follow-up (range = 6-76 months) demonstrated that twelve patients (38.7%) had complete remission, 18 patients (58.0%) still had significant proteinuria and only one had serum creatinine of 1.6 mg/dl at 42 months. One child progressed to end stage renal diseases during IPC therapy. Five patients had severe infections during the treatment resulting in one death. Hemorrhagic cystitis and malignancies were not found. CONCLUSION: Treatment of severe lupus nephritis in children with intravenous pulse cyclophosphamide is associated with favorable short term results. Severe infections are the major complications.

Adolescent↗
PubMed2000

Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies.

To evaluate the response rate and potential toxicities, a phase II trial was conducted of fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated low-grade and select intermediate-grade lymphoid malignancies. Symptomatic patients with preserved end organ function received cyclophosphamide 600 mg/m(2) intravenous (iv) day 1 and fludarabine 20 mg/m(2) iv days1 through 5, followed by filgrastim 5 microg/kg subcutaneous starting approximately day 8. Treatment was repeated every 28 days until maximum response or a maximum of 6 cycles. Sixty patients, median age 53.5 years, were enrolled. Thirty-seven patients with non-Hodgkin lymphoma (NHL) were stage IV and 6 were stage III. Eleven of 17 patients with chronic lymphocytic leukemia (CLL) were Rai intermediate risk and 6 were high risk. The overall complete response (CR) rate was 51% and the partial response (PR) rate was 41%. Of patients with CLL, 47% achieved a CR and the remaining 53% achieved a PR. Of patients with follicular lymphoma, 60% achieved CR and 32% achieved a PR. Although the toxicity of this regimen was mainly hematologic, significant nonhematologic toxicities, including infections, were seen. Twenty-four patients subsequently received an autologous or allogeneic stem cell transplant. Engraftment was rapid, and there were no noticeable procedure toxicities in the immediate posttransplant period attributable to the fludarabine and cyclophosphamide regimen. Fludarabine, cyclophosphamide, and filgrastim make up a highly active and well-tolerated regimen in CLL and NHL.

Adult↗
PubMed2000

Invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome--a case report.

We report a case of invasive bladder cancer after cyclophosphamide administration for nephrotic syndrome, and briefly discuss the association of bladder cancer and cyclophosphamide. A 6-year-old boy, who was diagnosed as having nephrotic syndrome, was treated with oral administration of prednisolone and cyclophosphamide for 4 years, receiving a total dose of 49.5 g cyclophosphamide. At age 27, a gross hematuria with bloody clots appeared and he presented with postrenal renal failure. He underwent a radical cystourethrectomy and ileal conduit for stage a pT3a pN0 M0 transitional cell carcinoma of the bladder. He was not given any adjuvant treatments because of his renal insufficiency, and he died from the disease 14 months after radical surgery.

Adult↗
PubMed2000

A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas.

Relapsed B-cell lymphomas are incurable with conventional chemotherapy and radiation therapy, although a fraction of patients can be cured with high-dose chemoradiotherapy and autologous stem-cell transplantation (ASCT). We conducted a phase I/II trial to estimate the maximum tolerated dose (MTD) of iodine 131 ((131)I)-tositumomab (anti-CD20 antibody) that could be combined with etoposide and cyclophosphamide followed by ASCT in patients with relapsed B-cell lymphomas. Fifty-two patients received a trace-labeled infusion of 1.7 mg/kg (131)I-tositumomab (185-370 MBq) followed by serial quantitative gamma-camera imaging and estimation of absorbed doses of radiation to tumor sites and normal organs. Ten days later, patients received a therapeutic infusion of 1.7 mg/kg tositumomab labeled with an amount of (131)I calculated to deliver the target dose of radiation (20-27 Gy) to critical normal organs (liver, kidneys, and lungs). Patients were maintained in radiation isolation until their total-body radioactivity was less than 0.07 mSv/h at 1 m. They were then given etoposide and cyclophosphamide followed by ASCT. The MTD of (131)I-tositumomab that could be safely combined with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide delivered 25 Gy to critical normal organs. The estimated overall survival (OS) and progression-free survival (PFS) of all treated patients at 2 years was 83% and 68%, respectively. These findings compare favorably with those in a nonrandomized control group of patients who underwent transplantation, external-beam total-body irradiation, and etoposide and cyclophosphamide therapy during the same period (OS of 53% and PFS of 36% at 2 years), even after adjustment for confounding variables in a multivariable analysis.

Adult↗
PubMed2000

Low-dose fludarabine and cyclophosphamide in elderly patients with B-cell chronic lymphocytic leukemia refractory to conventional therapy.

BACKGROUND AND OBJECTIVES: In recent years fludarabine alone or in combination with other drugs has been reported to be effective in the treatment of B-cell chronic lymphocytic leukemia (B-CLL), both as first line and salvage therapy. Among the different combination regimens, the association of fludarabine and cyclophosphamide has shown a considerable therapeutic efficacy, although a relevant number of infectious complications have been described, particularly in elderly patients. The aim of this work was to evaluate the efficacy, the toxicity, and the incidence of infectious episodes of a regimen combining lower doses of fludarabine and cyclophosphamide in elderly patients with B-CLL refractory to conventional therapy. DESIGN AND METHODS: Twenty patients with progressive B-CLL with a median age of 75 years (4 in stage B and 16 in stage C) and refractory to conventional therapy were enrolled in this study. The combination regimen was as follows: fludarabine 15 mg/m2/day i.v. [max 25 mg] and cyclophosphamide 200 mg/m2/day i.v. for four days. RESULTS: All patients enrolled were evaluable for response. Three out of 20 (15%) patients achieved a complete remission (CR), 14/20 (70%) a partial response (PR) with an overall response rate (CR+PR) of 85%, according to National Cancer Institute-Working Group response criteria. Three patients were considered resistant. In four out of 20 patients (20%), a severe neutropenia (neutrophils < 0.5x10(9)/L) occurred and one of them developed an infectious complication which required treatment with systemic antibiotics and granulocyte colony- stimulating factor (G-CSF). Non-hematologic toxicity was negligible in all patients but one, who despite a adequate therapy with allopurinol and hydration, experienced a tumor lysis syndrome with transient but severe renal impairment. INTERPRETATION AND CONCLUSIONS: The association of low-dose fludarabine and cyclophosphamide appeared to be effective in this subset of B-CLL patients, reproducing a similar overall response rate obtained with other fludarabine-based combination therapies. In addition, in this group of elderly patients, toxic side effects were negligible and infectious complications remarkably low.

Aged↗
PubMed2000

Phase II trial of cyclophosphamide, leucovorin, 5-fluorouracil 24-hour infusion and tamoxifen in pancreatic cancer.

Leucovorin modulates the cytotoxic effects of 5-fluorouracil (5-FU) in the treatment of cancer. 24-hour infusion of 5-FU has been shown to enhance antitumor activity in colorectal cancer compared to bolus infusion. According to experimental data cyclophosphamide and tamoxifen may enhance the effectiveness of leucovorin and 5-FU. A phase II trial was initiated to evaluate the effect of a combination of low-dose cyclophosphamide (C), leucovorin (L), 5-FU (F) and tamoxifen (T) (CLFT) in advanced pancreatic cancer. Fifty patients were treated monthly with 300 mg/m2 cyclophosphamide and weekly with 500 mg/m2 leucovorin followed by a 24-hour infusion of 2000 mg/m2 5-FU and tamoxifen 20 mg bid. Three patients had a partial response (6%), two a minor response (4%) and 32 (64%) no change of disease. The median survival time was 8.5 months for all patients, the median time to progression of disease was 4.6 months and the 1-year survival rate was 28%. CLFT was fairly well tolerated. These data suggest that biochemical modulation of 24-hour infusional 5-FU with leucovorin together with cyclophosphamide and tamoxifen has some positive effects in the treatment of pancreatic cancer.

Adenocarcinoma↗